glycogen and Hypoxia

Beyond storing and supplying energy in the liver and muscles, glycogen also plays critical roles in cell differentiation, signaling, redox regulation, and stemness under various physiological and pathophysiological conditions. Such versatile functions have been revealed by various forms of glycogen storage diseases. Here, we outline the source of carbon flux in glycogen metabolism and discuss how glycogen metabolism guides CD8

Topics: Animals; Brain; Energy Metabolism; Gluconeogenesis; Glucose; Glycogen; Glycogenolysis; Homeostasis; Humans; Hypoxia; Immunologic Memory; Liver; Macrophages; Muscle, Skeletal; Neoplasms; Pentose Phosphate Pathway; T-Lymphocytes

Metabolic reprogramming is a hallmark of cancer cells and contributes to their adaption within the tumour microenvironment and resistance to anticancer therapies. Recently, glycogen metabolism has become a recognised feature of cancer cells since it is upregulated in many tumour types, suggesting that it is an important aspect of cancer cell pathophysiology. Here, we provide an overview of glycogen metabolism and its regulation, with a focus on its role in metabolic reprogramming of cancer cells under stress conditions such as hypoxia, glucose deprivation and anticancer treatment. The various methods to detect glycogen in tumours in vivo as well as pharmacological modulators of glycogen metabolism are also reviewed. Finally, we discuss the therapeutic value of targeting glycogen metabolism as a strategy for combinational approaches in cancer treatment.

Topics: Animals; Antineoplastic Agents; Disease Progression; Energy Metabolism; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Glycogen; Humans; Hypoxia; Molecular Targeted Therapy; Neoplasms; Organ Specificity; Tumor Microenvironment

Most of the literature related to high altitude medicine is devoted to the short-term effects of high-altitude exposure on human physiology. However, long-term effects of living at high altitudes may be more important in relation to human disease because more than 400 million people worldwide reside above 1500 m. Interestingly, individuals living at higher altitudes have a lower fasting glycemia and better glucose tolerance compared with those who live near sea level. There is also emerging evidence of the lower prevalence of both obesity and diabetes at higher altitudes. The mechanisms underlying improved glucose control at higher altitudes remain unclear. In this review, we present the most current evidence about glucose homeostasis in residents living above 1500 m and discuss possible mechanisms that could explain the lower fasting glycemia and lower prevalence of obesity and diabetes in this population. Understanding the mechanisms that regulate and maintain the lower fasting glycemia in individuals who live at higher altitudes could lead to new therapeutics for impaired glucose homeostasis.

Topics: Adipose Tissue; Altitude; Diabetes Mellitus; Glucagon; Glucose; Glycogen; Homeostasis; Humans; Hyperinsulinism; Hypoglycemia; Hypoxia; Liver; Muscle, Skeletal; Obesity; Time Factors

In the second part of this two part article the neonatal energy triangle elements of hypoxia and hypothermia are explored and the physiology of the first few hours of neonatal life drawn together into an integrated whole. This framework can assist in understanding the three most common difficulties encountered by the preterm baby and directing integrated and holistic care.

Topics: Adaptation, Physiological; Blood Glucose; Body Temperature Regulation; Glycogen; Holistic Health; Homeostasis; Humans; Hypoglycemia; Hypothermia; Hypoxia; Infant, Newborn; Infant, Premature; Infant, Premature, Diseases; Neonatal Nursing; Oxygen Consumption; Respiratory Physiological Phenomena; Risk Factors; Work of Breathing

The turtle brain's extraordinary ability to tolerate anoxia is based on constitutive and expressed factors. Constitutive factors that predispose for anoxia tolerance include enhanced levels of glycogen stores, increased densities of protective receptors, elevated antioxidant capacities and elevated heat shock protein. However, to survive an anoxic insult, three distinct phases must be negotiated successfully. (1) A coordinated downregulation of ATP demand processes to basal levels. This phase, which takes 1-2 h, includes a reduction in voltage-gated K(+) (Kv) channel transcription and a substantial increase in Hsp72 and Hsc73 levels. During this period, adenosine and K(ATP) channels mediate several key events including channel arrest initiation and a reduction in the release of excitatory amino acids (EAAs). (2) Long-term survival (days) at basal levels of ATP expenditure. Neuronal network integrity is preserved through the continued operation of core activities. These include periodic electrical activity, an increased release of GABA and a continued release of glutamate and dopamine. Adenosine and GABA modulate the glutamate release. There is a further increase in Hsc73, indicating a 'housekeeping' role for this protein during this period. (3) A rapid upregulation of neuronal processes when oxygen becomes available to restore full function, together with the activation of protection mechanisms against reperfusion-generated reactive oxygen species.

Topics: Adenosine Triphosphate; Animals; Antioxidants; Brain; gamma-Aminobutyric Acid; Gene Expression Regulation; Glutamic Acid; Glycogen; Heat-Shock Proteins; Hypoxia; Models, Biological; Neurotransmitter Agents; Oxygen; Potassium Channels; Time Factors; Turtles

AMP-activated protein kinase (AMPK) is becoming recognized as a critical regulator of energy metabolism in cells. Using a mouse model in which we specifically blocked AMPK activity in muscles, we have demonstrated that activation of AMPK is necessary for the effects of 5-aminoimidazole-4-carboxamide riboside ('AICAR') and hypoxia, and is possibly required for a portion of exercise-induced glucose uptake. These same mice could not maintain sufficient glycogen in their skeletal muscle and it was rapidly depleted when the animals were subjected to mild exercise. Using isolated strips, we observed muscle hypertrophy and increased tiredness in the AMPK-deficient muscle. We also performed microarray analysis and showed dramatic changes of transcription profile in muscles of the lazy mice. These could have a significant impact on muscle function and may contribute to the observed phenotype.

Topics: Aminoimidazole Carboxamide; AMP-Activated Protein Kinases; Animals; Enzyme Inhibitors; Glycogen; Glycogen Synthase; Hypertrophy; Hypoxia; Mice; Multienzyme Complexes; Muscle, Skeletal; Mutation; Phenotype; Physical Conditioning, Animal; Protein Serine-Threonine Kinases; Ribonucleotides; Time Factors; Transcription, Genetic

The paper presents the author's own findings and data available in the literature concerning the intracellular mechanisms of conversion of fatty acids to glucose and glycogen in mammalian and human tissues in health and in disease. This conversion is considered by the author to be a regular adaptive response that maintains energy homeostasis in oxygen deficiency.

Topics: Animals; Energy Metabolism; Fatty Acids; Glucose; Glycogen; Homeostasis; Humans; Hypoxia; Intracellular Fluid

Many amphibians encounter conditions each winter when their body temperature is so low that normal activities are suspended and the animals enter into a state of torpor. In ice-covered ponds or lakes, oxygen levels may also become limiting, thereby forcing animals to endure prolonged periods of severe hypoxia or anoxia. Certain frogs (e.g. Rana temporaria) can dramatically suppress their metabolism in anoxia but are not as tolerant as other facultative vertebrate anaerobes (e.g. turtle, goldfish) of prolonged periods of complete O2 lack. Many overwintering amphibians do, however, tolerate prolonged bouts of severe hypoxia, relying exclusively on cutaneous gas exchange. Rana temporaria overwintering for 2 months in hypoxic water (PO2 approximately 25 mmHg) at 3 degrees C progressively reduce their blood PCO2 to levels characteristic of water-breathing fish. The result is that blood pH rises and presumably facilitates transcutaneous O2 transfer by increasing Hb O2-affinity. Even after months of severe hypoxia, there is no substantial build-up of lactate as the animals continue to rely on cutaneous gas exchange to satisfy the requirements of a suppressed aerobic metabolism. Our recent experiments have shown that the skeletal muscle of frogs oxyconforms in vitro to the amount of O2 available. The cellular basis for the oxyconformation of skeletal muscle is unknown, but the hypothesis driving our continuing experiments theories that metabolic suppression at a cellular level is synonymous with suppressed ion leak across cellular membranes.

Topics: Adaptation, Physiological; Adipose Tissue; Amphibians; Animals; Carbon Dioxide; Cell Membrane; Cold Temperature; Energy Metabolism; Epithelium; Glycogen; Hibernation; Homeostasis; Hydrogen-Ion Concentration; Hypoxia; Lipid Metabolism; Mammals; Muscle, Skeletal; Neurons; Oxygen; Rana temporaria; Seasons; Signal Transduction; Skin Physiological Phenomena; Species Specificity; Turtles; Water-Electrolyte Balance

In acclimatized humans at high altitude the reduction, compared to acute hypoxia, of the blood lactate concentration (la) at any absolute oxygen uptake (VO2), as well as the reduction of maximum la (lamax) after exhaustive exercise, compared to both acute hypoxia or normoxia, have been considered paradoxical, and these phenomena have therefore become known as the "lactate paradox". Since, at any given power output and VO2, mass oxygen transport to the contracting locomotor muscles is not altered by the process of acclimatization to high altitude, the gradual reduction in [la-]max in lowlanders exposed to chronic hypoxia seems not to be due to changes in oxygen availability at the tissue level. At present, it appears that the acclimatization-induced changes in [la-] during exercise are the result of at least two mechanisms: (1) a decrease in maximum substrate flux through aerobic glycolysis due to the reduced VO2max in hypoxia; and (2) alterations in the metabolic control of glycogenolysis and glycolysis at the cellular level, largely because of the changes in adrenergic drive of glycogenolysis that ensue during acclimatization, although effects of changes in peripheral oxygen transfer and the cellular redox state cannot be ruled out. With regard to the differences in lactate accumulation during exercise that have been reported to occur between lowlanders and highlanders, both groups either being acclimatized or not, these do not seem to be based upon fundamentally different metabolic features. Instead, they seem merely to reflect points along the same continuum of phenotypic adaptation of which the location depends on the time spent at high altitude.

Topics: Acclimatization; Altitude; Biological Transport, Active; Glycogen; Glycolysis; Humans; Hypoxia; Lactic Acid; Oxygen Consumption; Physical Exertion; Receptors, Adrenergic, beta; Tibet

Animal survival during severe hypoxia and/or anoxia is enhanced by a variety of biochemical adaptations including adaptations of fermentative pathways of energy production and, most importantly, the ability to sharply reduce metabolic rate by 5-20 fold and enter a hypometabolic state. The biochemical regulation of metabolic arrest is proving to have common molecular principles that extend across phylogenetic lines and that are conserved in different types of arrested states (not only anaerobiosis but also estivation, hibernation, etc.). Our new studies with anoxia-tolerant vertebrates have identified a variety of regulatory mechanisms involved in both metabolic rate depression and in the aerobic recovery process using as models the freshwater turtle Trachemys scripta elegans and garter snakes Thamnophis sirtalis parietalis. Mechanisms include: 1) post-translational modification of cellular and functional proteins by reversible phosphorylation and changes in protein kinase (PKA, PKC) and/or phosphatase activities to regulate this, 2) reversible enzyme binding associations with subcellular structural elements, 3) differential gene expression and/or mRNA translation producing new mRNA variants and new protein products, 4) changes in protease activity, particularly the multicatalytic proteinase complex, and 5) both constitutive and anoxia-induced modifications to cellular antioxidant systems to deal with oxidative stress during the anoxic-aerobic transition of recovery.

Topics: Adaptation, Physiological; Animals; Glycogen; Hypoxia; Phosphorylation; Protein Kinases; Proteins; Survival Rate; Turtles

Muscle contraction results in an increase in membrane permeability to glucose. The actual mechanism by which contractile activity increases membrane permeability is unknown. However, kinetic studies suggest that this increase is due to an increase in the number of glucose transporters associated with the plasma membrane. This is also suggested by the recent finding that cytochalsin B, which competitively inhibits the binding of glucose to the glucose transporter in the plasma membrane, prevents activation of the glucose transport process by muscle contraction. Unlike insulin-stimulated glucose transport, in which permeability is reversed rapidly upon removal of the insulin, the increase in membrane permeability following contractile activity can persist for many hours. It has also been reported that the stimulatory effects of insulin and contraction are additive, and that prostaglandin E2 augments the effect of insulin on glucose transport but has no effect on contraction-facilitated glucose transport. Collectively, these findings suggest that insulin and contractile activity increase membrane permeability to glucose by independent mechanisms. An increase in membrane permeability is only partially responsible for the increase in glucose uptake during exercise in vivo. With an increase in muscle activity, there is an increase in delivery of glucose and insulin to the muscle as a result of an increase in muscle blood flow. Glucose uptake may also be facilitated by an increase in the insulin sensitivity of the muscle. The increases in muscle blood flow and insulin sensitivity may be associated with activation of the kinin-prostaglandin system of the muscle. The increase in muscle insulin sensitivity may also involve an increase in insulin binding to its receptors on the sarcolemma. It should be noted that the increase in insulin binding associated with contractile activity requires the presence of epinephrine. Muscle glycogen may also affect the rate of glucose uptake during exercise. During prolonged, moderately intense exercise, glucose uptake increases as the muscle glycogen level declines. This increase in glucose uptake is inversely related to the glucose-6-phosphate concentration of the cell. During high-intensity exercise, the rate of glycogenolysis is rapid, resulting in the accumulation of glucose-6-phosphate and free glucose. Thus, it appears that the rate-limiting step in glucose uptake during exercise is shifted from transport to glucose phosphor

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Calcium; Glycogen; Humans; Hypoxia; Insulin; Monosaccharide Transport Proteins; Muscle Contraction; Muscles

The various phases of energy production have been described. These include glycolysis which is unique in its ability to produce ATP anaerobically, the tricarboxylic acid cycle with its major contribution to ATP production coming through the generation of NADH, and the cytochrome system at which reducing equivalents are converted to water, the released energy being incorporated into high-energy phosphates. The regulation of these pathways has been briefly described and the importance of the small amount of ATP generated anaerobically emphasized. The adaptation of muscle to periods of hypoxia through the presence of myoglobin, creatine phosphate and large amounts of glycogen is then discussed. The role of pH in limiting anaerobic glycolysis in muscle and the importance of the circulation in providing oxygen for exercising muscle are outlined. The effects of hypoxia on certain other tissues such as liver and brain have been detailed and finally methods for assessment of tissue hypoxia in man such as the measurement of the lactate:pyruvate ratio in blood are presented.

Topics: Acetyl Coenzyme A; Adenosine Triphosphate; Animals; Citric Acid Cycle; Cytochromes; Electron Transport; Glycogen; Glycolysis; Humans; Hypoxia; Lactates; Lipid Metabolism; Muscles; Myoglobin; NAD; Oxygen; Phosphocreatine; Physical Exertion; Regional Blood Flow

Topics: Acute Disease; Carbohydrate Metabolism; Energy Metabolism; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Insulin; Insulin Secretion; Myocardial Infarction; Myocardium; Oxidative Phosphorylation; Oxygen Consumption

Four possible metabolic approaches to improving cardiac function in the presence of myocardial hypoxia have been considered. 1. It appears that there is increasing evidence which suggests that free fatty acids are harmful to the ischemic heart. 2. Although it has been demonstrated that Krebs cycle intermediates can result in anaerobic energy formation by the mitochondria, and under certain extreme conditions can lead to improved performance of the heart, the potential for a physiologically important effect of this approach is probably limited. 3. The protection of the ischemic or hypoxic heart by alkalosis may be a feasible approach. The major beneficial effect appears to be exerted through more efficient conversion of energy that is already available to contractile performance rather than by increasing energy supply. 4. There appears to be some real potential for improving cardiac energy delivery via the glycolytic pathway. Calculations based on isolated rat heart studies indicate that, at 50% oxygenation, glycolytic ATP generation could totally correct for the deficit in mitochondrial ATP formation. Therefore, it is in the area of overcoming the inhibition of glycolytic ATP formation and tapping this potential metabolic pathway that energy delivery may be restored toward normal in the hypoxic and perhaps the borderline zone of underperfusion in the ischemic heart. The problem of the ischemic inhibition of glycolysis may partially be overcome by creating extracellular alkalosis, but this presumption will have to be tested.

Topics: Adenosine Triphosphate; Alkalosis; Anaerobiosis; Animals; Energy Metabolism; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycolysis; Heart; Hydrogen-Ion Concentration; Hypoxia; Mitochondria, Muscle; Myocardium; Reserpine; Stress, Mechanical

Topics: Adrenal Cortex Hormones; Animals; Anti-Inflammatory Agents; Arteries; Arteriosclerosis; Cats; Cattle; Cholesterol; Diabetes Complications; DNA; Epinephrine; Glycogen; Glycolysis; Humans; Hypertension; Hypoxia; Isoenzymes; L-Lactate Dehydrogenase; Lipid Metabolism; Oxidoreductases; Pentoses; Phosphofructokinase-1; Phospholipids; Phosphorylases; Rabbits; Rats; Swine; Thrombosis

Topics: Acidosis; Adenosine Triphosphate; Allosteric Site; Anaerobiosis; Animals; Arteries; Carbohydrate Metabolism; Cell Survival; Coronary Vessels; Creatine Kinase; Enzyme Activation; Fatty Acids; Glucose; Glycogen; Glycolysis; Heart; Hypoxia; Ischemia; Lactates; Mitochondria, Muscle; Myocardium; Necrosis; Oxidation-Reduction; Oxidative Phosphorylation; Phosphofructokinase-1; Phosphorylases; Veins

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; DNA; Fatty Acids, Nonesterified; Glycogen; Glycolysis; Humans; Hypoxia; Mitochondria, Muscle; Muscle Proteins; Myocardial Infarction; Myocardium; Oxidation-Reduction; Oxygen Consumption; Rats; Regeneration

Topics: Acetylcholine; Adenosine Triphosphate; Amines; Amino Acids; Anesthesia, Inhalation; Anesthetics; Animals; Brain; Brain Chemistry; Cyclopropanes; Glucose; Glycogen; Humans; Hypoxia; Ischemic Attack, Transient; Lactates; Nitrous Oxide; Oxygen Consumption; Phosphates; Synaptic Transmission

Topics: Acetylcholine; Amino Acids; Ammonia; Animals; Brain; Catecholamines; Cholesterol; Citric Acid Cycle; DNA; Electron Transport; Glycogen; Glycolysis; Humans; Hydrogen-Ion Concentration; Hypoxia; Ischemia; Lactates; Male; Monoamine Oxidase; Nerve Tissue Proteins; Neuraminic Acids; Oxidative Phosphorylation; Oxygen Consumption; Phospholipids; RNA

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aerobiosis; Anaerobiosis; Animals; Brain; Brain Neoplasms; Creatine; Ependymoma; Glioma; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Ischemia; Lactates; Meningioma; Mice; Neoplasms, Experimental; Neurilemmoma; Oxygen Consumption; Periodic Acid; Phosphofructokinase-1; Phosphorus; RNA; Vestibulocochlear Nerve

Acute myocardial infarction is viewed as a severe trauma causing a generalized metabolic reaction; an acute emotional stress with further metabolic implications; and a localized wound in which there is an acute increase in carbohydrate metabolism, followed by protein synthetic reactions leading to scar formation. The metabolic response is vital to the patient's successful adaptation to his myocardial infarction.

Topics: Adenosine Triphosphate; Adrenocorticotropic Hormone; Animals; Arrhythmias, Cardiac; Catecholamines; Cicatrix; Fatty Acids, Nonesterified; Glucose; Glycogen; Growth Hormone; Humans; Hydrocortisone; Hypoxia; Insulin; Insulin Secretion; Myocardial Infarction; Potassium; Stress, Physiological; Stress, Psychological

Topics: Adenine Nucleotides; Adenosine Triphosphate; Anaerobiosis; Animals; Catecholamines; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycolysis; Heart; Hydrogen-Ion Concentration; Hypoxia; Insulin; Ketone Bodies; Kinetics; Lactates; Myocardial Infarction; Myocardium; NADP; Oxygen Consumption

Topics: Animals; Animals, Newborn; Carbohydrate Metabolism; Female; Fetus; Gluconeogenesis; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Infant, Newborn; Lactates; Liver Glycogen; Muscles; Myocardium; Pregnancy

Electron-microscope studies of experimental models of myocardial ischaemia have provided basic information on the pathogenesis of hypoxic heart injury. Correlation of ultrastructural changes with biochemical data confirms the importance of catecholamine release and ionic shifts in the early evolution of ischaemic injury. An altered cellular metabolism induced by ischaemia causes rapid depletion of glycogen and is followed quickly by alterations in the nucleus, the mitochondria and the sarcotubular system; the myofibril is the organelle most resistant to hypoxia.Postmortem autolysis mimics early ischaemic change very closely and it probably has an initial hypoxic basis. Significant hypoxic-autolytic changes may begin during the agonal state. The time elapsing and the techniques of tissue preservation are critical in determining the amount of artefact. At present it is unrealistic to expect to obtain acutely ischaemic human myocardium soon enough after death to be of value in the estimation of the degree or duration of ischaemia by electron-microscope techniques. Rapidly progressive autolytic changes preclude the meaningful morphological assessment of hypoxic change at the ultrastructural level.

Topics: Animals; Cats; Coronary Disease; Disease Models, Animal; Dogs; Glycogen; Humans; Hypoxia; Magnesium Deficiency; Microscopy, Electron; Mitochondria; Myocardium; Myofibrils; Organoids; Postmortem Changes; Rabbits; Rats

Topics: Fatty Acids, Nonesterified; Glucose; Glucosyltransferases; Glycogen; Glycolysis; Heart Diseases; Heart Failure; Humans; Hydrogen-Ion Concentration; Hypoxia; Ketone Bodies; Lipid Metabolism; Myocarditis; Myocardium; Oxidative Phosphorylation; Phosphofructokinase-1; Pyruvates; Triglycerides

This study aimed to investigate the mechanisms known to regulate glucose homeostasis in human skeletal muscle of healthy and prediabetic subjects exercising in normobaric hypoxia. Seventeen healthy (H; 28.8 ± 2.4 yr; maximal oxygen consumption (V̇O

Topics: Adult; Anaerobic Threshold; Blood Glucose; Diabetes Mellitus, Type 2; Exercise; Glucose Tolerance Test; Glucose Transporter Type 4; Glycogen; Humans; Hypoxia; Insulin; Lipids; Male; Muscle, Skeletal; Prediabetic State

The present study was designed to determine the effect of 5 consecutive days of repeated sprint training under hypoxia on anaerobic performance and energy substances. Nineteen male sprinters performed repeated sprints for 5 consecutive days under a hypoxic (HYPO; fraction of inspired oxygen [F

Topics: Athletic Performance; Energy Intake; Energy Metabolism; Exercise Test; Glycogen; Humans; Hypoxia; Male; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine; Physical Conditioning, Human; Running; Time Factors; Young Adult

To investigate the effects of hypoxia acclimation, exercise training and fasting on the swimming performance of juvenile qingbo (Spinibarbus sinensis), we measured the critical swimming speed (U (crit)), resting and excess post-exercise oxygen consumption (EPOC) of control, hypoxia-acclimated, exercise-acclimated and fasting fish at 25°C. The muscle and plasma metabolites before and after a bout of exhaustive exercise (produced by chasing) were also measured. The fish were acclimated to hypoxia (48 h at 1.0 mg L(-1), 12.5% air saturation), exercise training (2 weeks at 60% of U (crit), 6 h daily) or fasting (2 weeks). All treatments resulted in significantly lower resting oxygen consumption ([Formula: see text]O(2rest)) but had no effect on the magnitude of EPOC. Hypoxia acclimation had no effect on U (crit) or peak post-exercise oxygen consumption ([Formula: see text]O(2peak)) but produced a higher depletion of muscle [glycogen] post-chasing (P < 0.05). Exercise training produced a significant increase in U (crit), higher liver [glycogen] pre-chasing and higher depletion of muscle [glycogen] post-chasing. Fasting resulted in a significant decrease in U (crit), [Formula: see text]O(2peak), muscle and liver [glycogen]. These results suggested that hypoxia acclimation had no effect on swimming performance in qingbo. Exercise training produced improved swimming performance by increasing the stored energy and the metabolic capacity of muscle. Fasting had a profound effect on swimming performance through both decreased respiratory capacity and a depleted energy store.

Topics: Acclimatization; Animals; Blood Glucose; Cyprinidae; Food Deprivation; Glycogen; Hypoxia; Lactic Acid; Liver; Muscle, Skeletal; Physical Conditioning, Animal; Swimming

We compared in human skeletal muscle the effect of absolute vs. relative exercise intensity on AMP-activated protein kinase (AMPK) signaling and substrate metabolism under normoxic and hypoxic conditions. Eight untrained males cycled for 30 min under hypoxic conditions (11.5% O(2), 111 +/- 12 W, 72 +/- 3% hypoxia Vo(2 peak); 72% Hypoxia) or under normoxic conditions (20.9% O(2)) matched to the same absolute (111 +/- 12 W, 51 +/- 1% normoxia Vo(2 peak); 51% Normoxia) or relative (to Vo(2 peak)) intensity (171 +/- 18 W, 73 +/- 1% normoxia Vo(2 peak); 73% Normoxia). Increases (P < 0.05) in AMPK activity, AMPKalpha Thr(172) phosphorylation, ACCbeta Ser(221) phosphorylation, free AMP content, and glucose clearance were more influenced by the absolute than by the relative exercise intensity, being greatest in 73% Normoxia with no difference between 51% Normoxia and 72% Hypoxia. In contrast to this, increases in muscle glycogen use, muscle lactate content, and plasma catecholamine concentration were more influenced by the relative than by the absolute exercise intensity, being similar in 72% Hypoxia and 73% Normoxia, with both trials higher than in 51% Normoxia. In conclusion, increases in muscle AMPK signaling, free AMP content, and glucose disposal during exercise are largely determined by the absolute exercise intensity, whereas increases in plasma catecholamine levels, muscle glycogen use, and muscle lactate levels are more closely associated with the relative exercise intensity.

Topics: Adult; AMP-Activated Protein Kinases; Biopsy, Fine-Needle; Blood Glucose; Catecholamines; Energy Metabolism; Exercise; Fatty Acids, Nonesterified; Glycerol; Glycogen; Heart Rate; Humans; Hypoxia; Insulin; Lactic Acid; Male; Multienzyme Complexes; Muscle, Skeletal; Phosphorylation; Protein Serine-Threonine Kinases; Signal Transduction

During the onset of exercise in hypoxia, the increased lactate accumulation is associated with a delayed activation of pyruvate dehydrogenase (PDH; Parolin ML, Spreit LL, Hultman E, Hollidge-Horvat MG, Jones NL, and Heigenhauser GJF. Am J Physiol Endocrinol Metab 278: E522-E534, 2000). The present study investigated whether activation of PDH with dichloroacetate (DCA) before exercise would reduce lactate accumulation during exercise in acute hypoxia by increasing oxidative phosphorylation. Six subjects cycled on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake after a saline (control) or DCA infusion while breathing 11% O(2). Muscle biopsies of the vastus lateralis were taken at rest and after 1 and 15 min of exercise. DCA increased PDH activity at rest and at 1 min of exercise, resulting in increased acetyl-CoA concentration and acetylcarnitine concentration at rest and at 1 min. In the first minute of exercise, there was a trend toward a lower phosphocreatine (PCr) breakdown with DCA compared with control. Glycogenolysis was lower with DCA, resulting in reduced lactate concentration ([lactate]), despite similar phosphorylase a mole fractions and posttransformational regulators. During the subsequent 14 min of exercise, PDH activity was similar, whereas PCr breakdown and muscle [lactate] were reduced with DCA. Glycogenolysis was lower with DCA, despite similar mole fractions of phosphorylase a, and was due to reduced posttransformational regulators. The results from the present study support the hypothesis that lactate production is due in part to metabolic inertia and cannot solely be explained by an oxygen limitation, even under conditions of acute hypoxia.

Topics: Acetyl Coenzyme A; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adult; Blood Glucose; Blood Pressure; Dichloroacetic Acid; Glycogen; Glycolysis; Heart Rate; Humans; Hypoxia; Lactic Acid; Male; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine; Phosphorylases; Physical Exertion; Pyruvate Dehydrogenase Complex; Respiratory Function Tests

Skeletal muscle metabolite depletion exists in advanced chronic obstructive pulmonary disease (COPD) patients with chronic hypoxaemia. The purpose of this study was to investigate if long-term oxygen therapy (LTOT) can improve skeletal muscle energy metabolism. Eight patients with advanced COPD, four with chronic hypoxaemia, were investigated using muscle biopsy specimens from the quadriceps femoris muscle applying the needle biopsy technique. The investigation was performed twice, before and after approximately 8 months of LTOT in the hypoxaemic patients. Eight healthy controls of similar age were also investigated. In the COPD patients, muscle glycogen, ATP and creatine phosphate (CrP) concentrations, were 42% (P < 0.01), 18% (P < 0.05) and 21% (P = n.s.) lower than in the healthy controls, respectively, while creatine (Cr) and lactate concentrations were 21% and 90% higher, respectively in the COPD patients compared to the healthy control subjects (P < 0.05). After LTOT, the 'energy index' CrP/(CrP + Cr) ratio increased by 0.12 in the LTOT patients but decreased by 0.12 in the control COPD patients (P < 0.05). The results indicate an improvement in skeletal muscle energy metabolism during LTOT in COPD patients with chronic hypoxaemia.

Topics: Adenosine Triphosphate; Aged; Creatine; Energy Metabolism; Female; Glycogen; Humans; Hypoxia; Lactates; Long-Term Care; Lung Diseases, Obstructive; Male; Middle Aged; Muscle, Skeletal; Oxygen Inhalation Therapy; Phosphocreatine

Five male subjects performed steady exercise on a cycle ergometer at an intensity of 60% maximal O2 uptake (VO2max) for 6 min on three separate occasions while breathing gas mixtures of 12,16 or 21% O2 in N2. Expired gas fractions, ventilation, heart rate, arterial O2 saturation (SaO2), blood lactate (La) and plasma catecholamines (epinephrine: E and norepinephrine: NE) were measured. O2 uptake (VO2) was calculated for the last minute of exercise. Blood samples were drawn at rest and immediately after exercise. By inspiring hypoxic gas mixtures, the SaO2 value decreased during exercise to 85.0 +/- 5.4 (16%) and 66.4 +/- 4.1 (12%) from 95.0 +/- 0.1 in normoxia. VO2 during exercise was not different among the three conditions. Exercise-induced La accumulation was increased by hypoxia. E and NE during exercise were not affected by hypoxia statistically. There was a significant correlation between La and E (P < 0.01) and between La and NE (P < 0.01) during exercise in the three conditions. The present findings suggest a relationship between glycogen metabolism and sympathoadrenal activity which results in an increase of plasma catecholamines during exercise in humans acutely exposed to hypoxia.

Topics: Administration, Inhalation; Adult; Catecholamines; Dose-Response Relationship, Drug; Exercise; Glycogen; Heart Rate; Humans; Hypoxia; Lactates; Male; Oxygen; Oxygen Consumption

Recent advancements in anatomical imaging of tumours as treatment targets have led to improvements in RT. However, it is unlikely that improved anatomical imaging alone will be the sole driver for new advances in personalised RT. Biochemically based radiobiological information is likely to be required for next-generation improvements in the personalisation of radiotherapy dose prescriptions to individual patients. In this paper, we use Raman spectroscopy (RS), an optical technique, to monitor individual biochemical response to radiation within a tumour microenvironment. We spatially correlate individual biochemical responses to augmentatively derived hypoxic maps within the tumour microenvironment. Furthermore, we pair RS with a data analytical framework combining (i) group and basis restricted non-negative matrix factorization (GBR-NMF), (ii) a random forest (RF) classifier, (iii) and a feature metric importance calculation method, Shapley Additive exPlanations (SHAP), in order to ascertain the relative importance of individual biochemicals in describing the overall biological response as observed with RS. The current study found that the GBR-NMF-RF-SHAP model helped identify a wide range of radiation response biomarkers and hypoxia indicators (

Topics: Biomarkers; Glycogen; Heterografts; Humans; Hypoxia; Machine Learning; Spectrum Analysis, Raman

This study investigated the effect of carbohydrate supplementation on substrate oxidation during exercise in hypoxia after preexercise breakfast consumption and omission.. Eleven men walked in normobaric hypoxia (FiO2 ~11.7%) for 90 min at 50% of hypoxic V˙O2max. Participants were supplemented with a carbohydrate beverage (1.2 g·min-1 glucose) and a placebo beverage (both enriched with U-13C6 D-glucose) after breakfast consumption and after omission. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate carbohydrate (exogenous and endogenous [muscle and liver]) and fat oxidation.. In the first 60 min of exercise, there was no significant change in relative substrate oxidation in the carbohydrate compared with placebo trial after breakfast consumption or omission (both P = 0.99). In the last 30 min of exercise, increased relative carbohydrate oxidation occurred in the carbohydrate compared with placebo trial after breakfast omission (44.0 ± 8.8 vs 28.0 ± 12.3, P < 0.01) but not consumption (51.7 ± 12.3 vs 44.2 ± 10.4, P = 0.38). In the same period, a reduction in relative liver (but not muscle) glucose oxidation was observed in the carbohydrate compared with placebo trials after breakfast consumption (liver, 7.7% ± 1.6% vs 14.8% ± 2.3%, P < 0.01; muscle, 25.4% ± 9.4% vs 29.4% ± 11.1%, P = 0.99) and omission (liver, 3.8% ± 0.8% vs 8.7% ± 2.8%, P < 0.01; muscle, 19.4% ± 7.5% vs 19.2% ± 12.2%, P = 0.99). No significant difference in relative exogenous carbohydrate oxidation was observed between breakfast consumption and omission trials (P = 0.14).. In acute normobaric hypoxia, carbohydrate supplementation increased relative carbohydrate oxidation during exercise (>60 min) after breakfast omission, but not consumption.

Topics: Blood Glucose; Breakfast; Breath Tests; Calorimetry, Indirect; Dietary Carbohydrates; Dietary Supplements; Energy Metabolism; Fatty Acids, Nonesterified; Glycogen; Heart Rate; Humans; Hypoxia; Lactic Acid; Lipid Metabolism; Liver; Male; Mass Spectrometry; Muscle, Skeletal; Oxidation-Reduction; Placebos; Time Factors; Walking; Young Adult

This study determined the effect of a single session of sprint interval training in hypoxia on muscle glycogen content among athletes.. Ten male college track and field sprinters (mean ± standard error of the mean: age, 21.1 ± 0.2 years; height, 177 ± 2 cm; body weight, 67 ± 2 kg) performed two exercise trials under either hypoxia [HYPO; fraction of inspired oxygen (F. Exercise significantly decreased muscle glycogen content in both trials (interaction, P = 0.03; main effect for time, P < 0.01). Relative changes in muscle glycogen content following exercise were significantly higher in the HYPO trial (- 43.5 ± 0.4%) than in the NOR trial (- 34.0 ± 0.3%; P < 0.01). The mean power output did not significantly differ between the two trials (P = 0.80). The blood lactate concentration after exercise was not significantly different between trials (P = 0.31).. A single session of sprint interval training (3 × 30 s sprints) in hypoxia caused a greater decrease in muscle glycogen content compared with the same exercise under normoxia without interfering with the power output.

Topics: Carbon Dioxide; Energy Metabolism; Exercise Test; Glycogen; High-Intensity Interval Training; Humans; Hypoxia; Lactates; Male; Muscle, Skeletal; Oxygen Consumption; Young Adult

Hypoxia is known to be commonly present in breast tumor microenvironments. Stem-like cells that repopulate breast tumors, termed tumor-repopulating cells (TRC), thrive under hypoxic conditions, but the underlying mechanism remains unclear. Here, we show that hypoxia promotes the growth of breast TRCs through metabolic reprogramming. Hypoxia mobilized transcription factors HIF1α and FoxO1 and induced epigenetic reprogramming to upregulate cytosolic phosphoenolpyruvate carboxykinase (PCK1), a key enzyme that initiates gluconeogenesis. PCK1 subsequently triggered retrograde carbon flow from gluconeogenesis to glycogenesis, glycogenolysis, and the pentose phosphate pathway. The resultant NADPH facilitated reduced glutathione production, leading to a moderate increase of reactive oxygen species that stimulated hypoxic breast TRC growth. Notably, this metabolic mechanism was absent in differentiated breast tumor cells. Targeting PCK1 synergized with paclitaxel to reduce the growth of triple-negative breast cancer (TNBC). These findings uncover an altered glycogen metabolic program in breast cancer, providing potential metabolic strategies to target hypoxic breast TRCs and TNBC. SIGNIFICANCE: Hypoxic breast cancer cells trigger self-growth through PCK1-mediated glycogen metabolism reprogramming that leads to NADPH production to maintain a moderate ROS level.

Topics: Animals; Biomarkers; Breast Neoplasms; Cell Line, Tumor; Cell Proliferation; Disease Models, Animal; Female; Gene Expression Regulation, Enzymologic; Gene Expression Regulation, Neoplastic; Gluconeogenesis; Glycogen; Humans; Hypoxia; Immunohistochemistry; Intracellular Signaling Peptides and Proteins; Metabolic Networks and Pathways; Mice; NADP; Phosphoenolpyruvate Carboxykinase (GTP); Reactive Oxygen Species

Polytrauma, with combined traumatic brain injury (TBI) and systemic damage are common among military and civilians. However, the pathophysiology of peripheral organs following polytrauma is poorly understood. Using a rat model of TBI combined with hypoxemia and hemorrhagic shock, we studied the status of peripheral redox systems, liver glycogen content, creatinine clearance, and systemic inflammation. Male Sprague-Dawley rats were subjected to hypoxemia and hemorrhagic shock insults (HH), penetrating ballistic-like brain injury (PBBI) alone, or PBBI followed by hypoxemia and hemorrhagic shock (PHH). Sham rats received craniotomy only. Biofluids and liver, kidney, and heart tissues were collected at 1 day, 2 days, 7 days, 14 days, and 28 days post-injury (DPI). Creatinine levels were measured in both serum and urine. Glutathione levels, glycogen content, and superoxide dismutase (SOD) and cytochrome C oxidase enzyme activities were quantified in the peripheral organs. Acute inflammation marker serum amyloid A-1 (SAA-1) level was quantified using western blot analysis. Urine to serum creatinine ratio in PHH group was significantly elevated on 7-28 DPI. Polytrauma induced a delayed disruption of the hepatic GSH/GSSG ratio, which resolved within 2 weeks post-injury. A modest decrease in kidney SOD activity was observed at 2 weeks after polytrauma. However, neither PBBI alone nor polytrauma changed the mitochondrial cytochrome C oxidase activity. Hepatic glycogen levels were reduced acutely following polytrauma. Acute inflammation marker SAA-1 showed a significant increase at early time-points following both systemic and brain injury. Overall, our findings demonstrate temporal cytological/tissue level damage to the peripheral organs due to combined PBBI and systemic injury.

Topics: Animals; Cytochromes c; Disease Models, Animal; Glutathione; Glycogen; Head Injuries, Penetrating; Hypoxia; Kidney; Liver; Male; Myocardium; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Superoxide Dismutase

Production of industrial effluents have led to increased copper (Cu) pollution of aquatic ecosystems, impacting the physiology of aquatic vertebrates. Past work has shown that Cu exerts its toxicity by disruption ion regulation and/ or increasing oxidative stress. However, it remains unclear how Cu may influence aerobic metabolism and hypoxia tolerance, two possible targets of its toxicity. To address this issue, we exposed freshwater acclimated killifish (F. heteroclitus) to a 96 h Cu exposure at a target concentration of 100 μg L

Topics: Acclimatization; Anaerobiosis; Animals; Copper; Ecosystem; Fresh Water; Fundulidae; Glycogen; Hypoxia; Lactic Acid; Muscles; Oxidative Stress; Oxygen Consumption; Physical Exertion; Water Pollutants, Chemical

Posttraumatic stress disorder (PTSD) causes mental and somatic diseases. Intermittent hypoxic conditioning (IHC) has cardio-, vaso-, and neuroprotective effects and alleviates experimental PTSD. IHC's ability to alleviate harmful PTSD effects on rat heart, liver, and brain was examined. PTSD was induced by 10-day exposure to cat urine scent (PTSD rats). Some rats were then adapted to 14-day IHC (PTSD+IHC rats), while PTSD and untreated control rats were cage rested. PTSD rats had a higher anxiety index (AI, X-maze test), than control or PTSD+IHC rats. This higher AI was associated with reduced glycogen content and histological signs of metabolic and hypoxic damage and of impaired contractility. The livers of PTSD rats had reduced glycogen content. Liver and blood alanine and aspartate aminotransferase activities of PTSD rats were significantly increased. PTSD rats had increased norepinephrine concentration and decreased monoamine oxidase A activity in cerebral cortex. The PTSD-induced elevation of carbonylated proteins and lipid peroxidation products in these organs reflects oxidative stress, a known cause of organ pathology. IHC alleviated PTSD-induced metabolic and structural injury and reduced oxidative stress. Therefore, IHC is a promising preventive treatment for PTSD-related morphological and functional damage to organs, due, in part, to IHC's reduction of oxidative stress.

Topics: Alanine Transaminase; Animals; Anxiety; Aspartate Aminotransferases; Behavior Rating Scale; Brain; Cats; Cerebral Cortex; Disease Models, Animal; Glycogen; Hypoxia; Liver; Male; Maze Learning; Monoamine Oxidase; Myocardium; Norepinephrine; Odorants; Oxidative Stress; Rats; Rats, Wistar; Stress Disorders, Post-Traumatic; Urine

Stored muscle carbohydrate supply and energetic efficiency constrain muscle functional capacity during exercise and are influenced by common physiological variables (e.g. age, diet, and physical activity level). Whether these constraints affect overall functional capacity or the timing of muscle energetic failure during acute hypoxia is not known. We interrogated skeletal muscle contractile properties in two anatomically distinct rodent hindlimb muscles that have well characterized differences in energetic efficiency (locomotory- extensor digitorum longus (EDL) and postural- soleus muscles) following a 24 hour fasting period that resulted in substantially reduced muscle carbohydrate supply. 180 mins of acute hypoxia resulted in complete energetic failure in all muscles tested, indicated by: loss of force production, substantial reductions in total adenosine nucleotide pool intermediates, and increased adenosine nucleotide degradation product-inosine monophosphate (IMP). These changes occurred in the absence of apparent myofiber structural damage assessed histologically by both transverse section and whole mount. Fasting and the associated reduction of the available intracellular carbohydrate pool (~50% decrease in skeletal muscle) did not significantly alter the timing to muscle functional impairment or affect the overall force/work capacities of either muscle type. Fasting resulted in greater passive tension development in both muscle types, which may have implications for the design of pre-clinical studies involving optimal timing of reperfusion or administration of precision therapeutics.

Topics: Adenine Nucleotides; Animals; Energy Metabolism; Fasting; Glycogen; Hypoxia; Male; Mice; Mice, Inbred BALB C; Muscle Contraction; Muscle, Skeletal; Physical Conditioning, Animal

Codonopsis pilosula is a traditional Chinese medicine and food supplement that is widely used in China. This study aimed to investigate the antifatigue and antihypoxia activities of different extracts and fractions from C. pilosula, including ethanol extract (ETH), water extract (WAT), polysaccharides (POL), inulin (INU) and oligosaccharides (OLI). Different extracts and fractions were orally administered to mice at the doses of 0.25, 0.5 and 1.0 g kg-1 once a day for 21 days. Antifatigue activity was assessed through the weight-loaded swimming test on the 21st day, and antihypoxia activity was evaluated through the normobarie hypoxia test on the following day. Finally, biochemical parameters, such as liver glycogen (LG), muscle glycogen (MG), blood urea nitrogen (BUN), lactic dehydrogenase (LDH), malondialdehyde (MDA), and glutathione (GSH) levels, were determined. The results showed that, compared with the control treatment, only POL treatment significantly prolonged the swimming time of the mice. POL groups had the strongest hypoxia tolerance, followed by the OLI and WAT groups. The levels of LG and MG were significantly increased by treatment with POL at the doses of 0.5 and 1.0 g kg-1, whereas BUN and LDH levels in POL groups were significantly lower than those in the control group. MDA under POL and OLI treatment was significantly lower than that under the control treatment. In addition, treatments with POL and OLI, except for treatment with a low dose of OLI, significantly increased GSH levels. In conclusion, POL could efficiently enhance antifatigue and antihypoxia abilities by increasing energy resources, decreasing detrimental metabolite accumulation, and enhancing antioxidant activity. OLI could improve antihypoxia activity by preventing lipid peroxidation and enhancing antioxidant activity.

Topics: Animals; Antioxidants; Body Weight; China; Codonopsis; Dietary Supplements; Disease Models, Animal; Eating; Energy Metabolism; Fatigue; Glutathione; Glycogen; Hypoxia; Lipid Peroxidation; Liver; Male; Malondialdehyde; Mice; Mice, Inbred ICR; Oligosaccharides; Plant Extracts; Polysaccharides; Swimming

Animals have evolved responses to low oxygen conditions to ensure their survival. Here, we have identified the C. elegans zinc finger transcription factor PQM-1 as a regulator of the hypoxic stress response. PQM-1 is required for the longevity of insulin signaling mutants, but surprisingly, loss of PQM-1 increases survival under hypoxic conditions. PQM-1 functions as a metabolic regulator by controlling oxygen consumption rates, suppressing hypoxic glycogen levels, and inhibiting the expression of the sorbitol dehydrogenase-1 SODH-1, a crucial sugar metabolism enzyme. PQM-1 promotes hypoxic fat metabolism by maintaining the expression of the stearoyl-CoA desaturase FAT-7, an oxygen consuming, rate-limiting enzyme in fatty acid biosynthesis. PQM-1 activity positively regulates fat transport to developing oocytes through vitellogenins under hypoxic conditions, thereby increasing survival rates of arrested progeny during hypoxia. Thus, while pqm-1 mutants increase survival of mothers, ultimately this loss is detrimental to progeny survival. Our data support a model in which PQM-1 controls a trade-off between lipid metabolic activity in the mother and her progeny to promote the survival of the species under hypoxic conditions.

Topics: Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Embryo, Mammalian; Gene Expression Regulation; Glycogen; Hypoxia; Insulin; Larva; Lipid Metabolism; Mutation; Oxygen Consumption; Signal Transduction; Stress, Physiological; Survival Analysis; Trans-Activators; Transcription, Genetic; Vitellogenins

Development of white striping (WS) and wooden breast (WB) in broiler breast meat have been linked to hypoxia, but their etiologies are not fully understood. This study aimed at investigating absolute expression of hypoxia-inducible factor-1 alpha subunit (HIF1A) and genes involved in stress responses and muscle repair using a droplet digital polymerase chain reaction. Total RNA was isolated from pectoralis major collected from male 6-week-old medium (carcass weight ≤ 2.5 kg) and heavy (carcass weight > 2.5 kg) broilers. Samples were classified as "non-defective" (n = 4), "medium-WS" (n = 6), "heavy-WS" (n = 7) and "heavy-WS+WB" (n = 3) based on abnormality scores. The HIF1A transcript was up-regulated in all of the abnormal groups. Transcript abundances of genes encoding 6-phosphofructo-2-kinase/fructose-2,6-biphosphatase 4 (PFKFB4), lactate dehydrogenase-A (LDHA), and phosphorylase kinase beta subunit (PHKB) were increased in heavy-WS but decreased in heavy-WS+WB. Glyceraldehyde-3-phosphate dehydrogenase (GAPDH) was up-regulated in non-defective samples. The muscle-specific mu-2 isoform of glutathione S-transferases (GSTM2) was up-regulated in the abnormal samples, particularly in the heavy groups. The genes encoding myogenic differentiation (MYOD1) and myosin light chain kinase (MYLK) exhibited similar expression pattern, of which medium-WS and heavy-WS significantly increased compared to non-defective whereas expression in heavy-WS+WB was not different from either non-defective or WS-affected group. The greatest and the lowest levels of calpain-3 (CAPN3) and delta-sarcoglycan (SCGD) were observed in heavy-WS and heavy-WS+WB, respectively. Based on micrographs, the abnormal muscles primarily comprised fibers with cross-sectional areas ranging from 2,000 to 3,000 μm2. Despite induced glycolysis at the transcriptional level, lower stored glycogen in the abnormal muscles corresponded with the reduced lactate and higher pH within their meats. The findings support hypoxia within the abnormal breasts, potentially associated with oversized muscle fibers. Between WS and WB, divergent glucose metabolism, cellular detoxification and myoregeneration at the transcriptional level could be anticipated.

Topics: Animals; Chickens; Gene Expression Regulation; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lactic Acid; Male; Muscle, Skeletal; Muscular Diseases; Pectoralis Muscles; Poultry Diseases; RNA, Messenger

Elite endurance athletes are used to train under hypoxic/high-altitude conditions, which can elicit certain stress responses in skeletal muscle and helps to improve their physical performance. Nuclear factor erythroid 2-related factor 2 (Nrf2) regulates cellular redox homeostasis and metabolism in skeletal muscle, playing important roles in adaptation to various stresses. In this study, Nrf2 knockout (KO) and wild-type (WT) mice were preconditioned to 48 h of hypoxia exposure (11.2% oxygen), and the effects of hypoxia preconditioning (HP) on exercise capacity and exercise-induced changes of antioxidant status, energetic metabolism, and mitochondrial adaptation in skeletal muscle were evaluated. Nrf2 knockout (KO) and wild-type (WT) mice were exposed to normoxia or hypoxia for 48 h before taking incremental treadmill exercise to exhaustion under hypoxia. The skeletal muscles were collected immediately after the incremental treadmill exercise to evaluate the impacts of HP and Nrf2 on the exercise-induced changes. The results indicate the absence of Nrf2 did not affect exercise capacity, although the mRNA expression of certain muscular genes involved in antioxidant, glycogen and fatty acid catabolism was decreased in Nrf2 KO mice. However, 48-h HP enhanced exercise capacity in WT mice but not in Nrf2 KO mice, and the exercise capacity of WT mice was significantly higher than that of Nrf2 KO mice. These findings suggest HP promotes exercise capacity of mice with the participation of the Nrf2 signal in skeletal muscle.

Topics: Acetyl-CoA Carboxylase; AMP-Activated Protein Kinases; Animals; Antioxidants; Exercise Tolerance; Glycogen; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Kelch-Like ECH-Associated Protein 1; Lipid Metabolism; Male; Mice, Inbred C57BL; Mice, Knockout; Mitochondria, Muscle; Muscle, Skeletal; NF-E2-Related Factor 2; Physical Conditioning, Animal

In breast cancer, tumor hypoxia has been linked to poor prognosis and increased metastasis. Hypoxia activates transcriptional programs in cancer cells that lead to increased motility and invasion, as well as various metabolic changes. One of these metabolic changes, an increase in glycogen metabolism, has been further associated with protection from reactive oxygen species damage that may lead to premature senescence. Here we report that breast cancer cells significantly increase glycogen stores in response to hypoxia. We found that knockdown of the brain isoform of an enzyme that catalyzes glycogen breakdown, glycogen phosphorylase B (PYGB), but not the liver isoform, PYGL, inhibited glycogen utilization in estrogen receptor negative and positive breast cancer cells; whereas both independently inhibited glycogen utilization in the normal-like breast epithelial cell line MCF-10A. Functionally, PYGB knockdown and the resulting inhibition of glycogen utilization resulted in significantly decreased wound-healing capability in MCF-7 cells and a decrease in invasive potential of MDA-MB-231 cells. Thus, we identify PYGB as a novel metabolic target with potential applications in the management and/or prevention of metastasis in breast cancer.

Topics: Breast Neoplasms; Cell Line, Tumor; Female; Gene Knockdown Techniques; Glycogen; Humans; Hypoxia; Metabolic Networks and Pathways; Neoplasm Metastasis; Neoplasm Staging; Phenotype; Phosphorylase b; Protein Isoforms; RNA Interference; RNA, Small Interfering

Cancer cells respond to hypoxia by upregulating the hypoxia-inducible factor 1α (HIF1A) transcription factor, which drives survival mechanisms that include metabolic adaptation and induction of angiogenesis by VEGF. Pancreatic tumors are poorly vascularized and severely hypoxic. To study the angiogenic role of HIF1A, and specifically probe whether tumors are able to use alternative pathways in its absence, we created a xenograft mouse tumor model of pancreatic cancer lacking HIF1A. After an initial delay of about 30 days, the HIF1A-deficient tumors grew as rapidly as the wild-type tumors and had similar vascularization. These changes were maintained in subsequent passages of tumor xenografts

Topics: Animals; Cell Line, Tumor; Cell Proliferation; Glycogen; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Inflammation; Mice; Mice, Inbred NOD; Mice, SCID; Neovascularization, Pathologic; Pancreas; Pancreatic Neoplasms; Signal Transduction

To study the effects of Fomes officinalis Ames. polysaccharides(FOPS) on anti-fatigue and hypoxia tolerance in mice.. Forty-eight mice were randomly divided into control group, low-dose, middle-dose and high-dose group of FOPS (100, 200, 400 mg/kg). All mice were orally administered by 0.20 ml/10 g, once a day for 21 consecutive days. The effects of different doses of FOPS on the loaded-swimming time, the content of serum urea nitrogen, the blood lactic acid, the hepatic glycogen and the muscle glycogen after exercise, the survival time under hypoxia at normal pressure and the maintenance time after decapitation were observed.. FOPS could significantly prolong the loaded-swimming time, decrease the contents of serum urea nitrogen , blood lactic acid and increase the contents of hepatic glycogen and muscle glycogen, significantly prolong the survival time under hypoxia and the maintenance time after decapitation comparing with the control group. Compared with the control group, FOPS could prolong the weight-bearing swimming time, anti-hypoxia survival time and respiratory maintenance time of mice after decapitation in a dose-dependent manner (P＜0.05 or 0.01). FOPS could decrease the contents of serum urea nitrogen and blood lactic acid, and increase the contents of hepatic glycogen and muscle glycogen in exercise mice, and most of them were significantly different (P＜0.05) or extremely significant (P＜0.01).. FOPS has anti-fatigue effects and can improve hypoxia tolerance.

Topics: Animals; Blood Urea Nitrogen; Coriolaceae; Fatigue; Glycogen; Hypoxia; Lactic Acid; Liver; Mice; Plant Extracts; Polysaccharides; Swimming

Pulmonary interstitial glycogenosis (PIG) is a rare infant interstitial lung disease characterized by an increase in the number of interstitial mesenchymal cells, presenting as enhanced cytoplasmic glycogen, and is considered to represent the expression of an underlying lung development disorder.. This study describes the clinical, radiological, and functional characteristics and long-term outcomes (median 12 years) of nine infants diagnosed with isolated PIG associated with alveolar simplification in the absence of other diseases.. All patients presented with tachypnea. Additionally, seven patients had breathing difficulties and hypoxemia. Abnormalities in chest-computerized tomography (CT) with a pattern of ground-glass opacity, septal thickening, and air trapping were observed in all individuals, with images suggesting abnormal alveolar growth (parenchymal bands and architectural distortion). All lung biopsies showed alveolar simplification associated with an increased number of interstitial cells, which appeared as accumulated cytoplasmic glycogen. In the follow-up, all patients were asymptomatic. The respiratory function test was normal in only two patients. Five children showed an obstructive pattern, and two children showed a restrictive pattern. Chest-CT, performed after an average of 6.5 years since the initial investigation, revealed a partial improvement of the ground-glass opacity pattern; however, relevant alterations persisted.. Although the patients with PIG in the absence of other associated pathologies had a good clinical outcome, significant radiographic alterations and sequelae in lung function were still observed after a median follow-up of 12 years, suggesting that PIG is a marker of some other persistent abnormalities in lung growth, which have effects beyond the symptomatic period.

Topics: Biopsy; Child; Child, Preschool; Cytoplasm; Disease Progression; Dyspnea; Female; Follow-Up Studies; Glycogen; Glycogen Storage Disease; Humans; Hypoxia; Infant; Infant, Newborn; Lung; Lung Diseases, Interstitial; Male; Pulmonary Alveoli; Tachypnea; Tomography, X-Ray Computed; Treatment Outcome

This study compared the coingestion of glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at terrestrial high altitude (HA) versus sea level, in women.. Five women completed two bouts of cycling at the same relative workload (55% Wmax) for 120 min on acute exposure to HA (3375 m) and at sea level (~113 m). In each trial, participants ingested 1.2 g·min of glucose (enriched with C glucose) and 0.6 g·min of fructose (enriched with C fructose) before and every 15 min during exercise. Indirect calorimetry and isotope ratio mass spectrometry were used to calculate fat oxidation, total and exogenous carbohydrate oxidation, plasma glucose oxidation, and endogenous glucose oxidation derived from liver and muscle glycogen.. The rates and absolute contribution of exogenous carbohydrate oxidation was significantly lower at HA compared with sea level (effect size [ES] > 0.99, P < 0.024), with the relative exogenous carbohydrate contribution approaching significance (32.6% ± 6.1% vs 36.0% ± 6.1%, ES = 0.56, P = 0.059) during the second hour of exercise. In comparison, no significant differences were observed between HA and sea level for the relative and absolute contributions of liver glucose (3.2% ± 1.2% vs 3.1% ± 0.8%, ES = 0.09, P = 0.635 and 5.1 ± 1.8 vs 5.4 ± 1.7 g, ES = 0.19, P = 0.217), and muscle glycogen (14.4% ± 12.2% vs 15.8% ± 9.3%, ES = 0.11, P = 0.934 and 23.1 ± 19.0 vs 28.7 ± 17.8 g, ES = 0.30, P = 0.367). Furthermore, there was no significant difference in total fat oxidation between HA and sea level (66.3 ± 21.4 vs 59.6 ± 7.7 g, ES = 0.32, P = 0.557).. In women, acute exposure to HA reduces the reliance on exogenous carbohydrate oxidation during cycling at the same relative exercise intensity.

Topics: Altitude; Bicycling; Blood Glucose; Energy Drinks; Energy Metabolism; Exercise; Female; Fructose; Glycogen; Humans; Hypoxia; Liver Glycogen; Muscle, Skeletal; Oxidation-Reduction

Kosaku, Kazuhiro, Tomonori Harada, Toyoharu Jike, Isao Tsuboi, and Shin Aizawa. Long-term hypoxic tolerance in murine cornea. High Alt Med Biol 19:35-41, 2018.. The cornea is believed to be an exceedingly sensitive organ to decreases in atmospheric oxygen concentrations. Previous corneal studies have shown the hypoxic tolerance of the cornea during short-term and local hypoxic exposure. This study investigated the tolerance of the cornea during long-term and systemic hypoxia.. Mice were bred under normobaric normoxia or hypoxia (10% oxygen concentration) conditions for 140 days. The layer structure, surface microvilli, and glycogen granules in the corneal epithelium were examined on day 2 and on day 140. The layer and surface structures of the corneal epithelium were normally maintained during the long-term hypoxia. Hypoxic stress caused a decrease in the glycogen granules in the corneal epithelial cells.. Maintenance of normal structures during long-term hypoxia suggests that the cornea has a high tolerance for hypoxic stress. The quantity of glycogen in corneal epithelial cells is considered an index of corneal hypoxia resistance.

Topics: Animals; Atmospheric Pressure; Cornea; Epithelium; Female; Glycogen; Hypoxia; Mice; Mice, Inbred C57BL; Microscopy, Electron, Scanning; Time Factors

Many fish experience daily cycles of hypoxia in the wild, but the physiological strategies for coping with intermittent hypoxia are poorly understood. We examined how killifish adjust O

Topics: Acclimatization; Anaerobiosis; Animals; Fundulidae; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lactic Acid; Oxygen Consumption

This study compared the effects of coingesting glucose and fructose on exogenous and endogenous substrate oxidation during prolonged exercise at altitude and sea level, in men. Seven male British military personnel completed two bouts of cycling at the same relative workload (55% W

Topics: Adipose Tissue; Adult; Altitude; Animals; Blood Glucose; Calorimetry, Indirect; Carbon Isotopes; Dietary Carbohydrates; Energy Metabolism; Exercise; Food, Fortified; Fructose; Glucose; Glycogen; Humans; Hypoxia; Liver; Male; Muscle, Skeletal; Oxidation-Reduction; Oxygen Consumption

Topics: Adrenal Medulla; Animals; Blood Glucose; Diabetes Mellitus, Type 2; Disease Models, Animal; Fasting; Glucose; Glucose Tolerance Test; Glycogen; Hypoxia; Insulin; Insulin Resistance; Liver; Male; Mice; Mice, Inbred C57BL; Oxygen; Oxyhemoglobins; Sleep Apnea, Obstructive

Increasing studies have shown protective effects of intermittent hypoxia on brain injury and heart ischemia. However, the effect of intermittent hypoxia on blood glucose metabolism, especially in diabetic conditions, is rarely observed. The aim of this study was to investigate whether intermittent hypoxia influences blood glucose metabolism in type 1 diabetic rats. Streptozotocin-induced diabetic adult rats and age-matched control rats were treated with intermittent hypoxia (at an altitude of 3 km, 4 h per day for 3 weeks) or normoxia as control. Fasting blood glucose, body weight, plasma fructosamine, plasma insulin, homeostasis model assessment of insulin resistance (HOMA-IR), pancreas β-cell mass, and hepatic and soleus glycogen were measured. Compared with diabetic rats before treatment, the level of fasting blood glucose in diabetic rats after normoxic treatment was increased (19.88 ± 5.69 mmol/L vs. 14.79 ± 5.84 mmol/L, p < 0.05), while it was not different in diabetic rats after hypoxic treatment (13.14 ± 5.77 mmol/L vs. 14.79 ± 5.84 mmol/L, p > 0.05). Meanwhile, fasting blood glucose in diabetic rats after hypoxic treatment was also lower than that in diabetic rats after normoxic treatment (13.14 ± 5.77 mmol/L vs. 19.88 ± 5.69 mmol/L, p<0.05). Plasma fructosamine in diabetic rats receiving intermittent hypoxia was significantly lower than that in diabetic rats receiving normoxia (1.28 ± 0.11 vs. 1.39 ± 0.11, p < 0.05), while there were no significant changes in body weight, plasma insulin and β-cell mass. HOMA-IR in diabetic rats after hypoxic treatment was also lower compared with diabetic rats after normoxic treatment (3.48 ± 0.48 vs. 3.86 ± 0.42, p < 0.05). Moreover, intermittent hypoxia showed effect on the increase of soleus glycogen but not hepatic glycogen. We conclude that intermittent hypoxia maintains glycemia in streptozotocin-induced diabetic rats and its regulation on muscular glycogenesis may play a role in the underlying mechanism.

Topics: Animals; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Diabetes Mellitus, Type 1; Fructosamine; Glycogen; Humans; Hypoxia; Insulin; Insulin Resistance; Insulin-Secreting Cells; Liver; Male; Muscle, Skeletal; Rats

All organisms live in temporally fluctuating environments. Theory predicts that the evolution of deterministic maternal effects (i.e., anticipatory maternal effects or transgenerational phenotypic plasticity) underlies adaptation to environments that fluctuate in a predictably alternating fashion over maternal-offspring generations. In contrast, randomizing maternal effects (i.e., diversifying and conservative bet-hedging), are expected to evolve in response to unpredictably fluctuating environments. Although maternal effects are common, evidence for their adaptive significance is equivocal since they can easily evolve as a correlated response to maternal selection and may or may not increase the future fitness of offspring. Using the hermaphroditic nematode Caenorhabditis elegans, we here show that the experimental evolution of maternal glycogen provisioning underlies adaptation to a fluctuating normoxia-anoxia hatching environment by increasing embryo survival under anoxia. In strictly alternating environments, we found that hermaphrodites evolved the ability to increase embryo glycogen provisioning when they experienced normoxia and to decrease embryo glycogen provisioning when they experienced anoxia. At odds with existing theory, however, populations facing irregularly fluctuating normoxia-anoxia hatching environments failed to evolve randomizing maternal effects. Instead, adaptation in these populations may have occurred through the evolution of fitness effects that percolate over multiple generations, as they maintained considerably high expected growth rates during experimental evolution despite evolving reduced fecundity and reduced embryo survival under one or two generations of anoxia. We develop theoretical models that explain why adaptation to a wide range of patterns of environmental fluctuations hinges on the existence of deterministic maternal effects, and that such deterministic maternal effects are more likely to contribute to adaptation than randomizing maternal effects.

Topics: Adaptation, Biological; Animals; Biological Evolution; Caenorhabditis elegans; Environment; Female; Glycogen; Hypoxia; Maternal Exposure; Sodium Chloride

To investigate the effect of acceleration rates on the constant acceleration test speed (U cat) and to compare U cat with the critical swimming speed (U crit) in Chinese bream (Parabramis pekinensis), the U cat test at acceleration rates of 0.05, 0.1, 0.2, 0.4 and 0.8 cm s(-2) and the U crit test in juvenile fish at 20 °C in either normoxia (>90 % saturation oxygen tension) or hypoxia (30 % saturation) were compared. The lactate concentration ([lactate]) of white muscle, liver and plasma and the glycogen concentration ([glycogen]) of white muscle and liver were also measured to identify whether tissue substrate depletion or tissue lactate accumulation correlated with exhaustion. The U cat decreased with the acceleration rate, and there was no significant difference between U crit and U cat at lower acceleration rates. Hypoxia resulted in lower U cat and U crit, and the difference increased with decreased acceleration rates of the U cat test, possibly due to the increased contribution of aerobic components in U crit or U cat at low acceleration rates. Hypoxia elicited a significant decrease in muscle [glycogen] and an increase in muscle and liver [lactate] in resting fish. All post-exercise fish had similar muscle [lactate], suggesting that tissue lactate accumulation may correlate with exercise exhaustion. Unlike hypoxia, exercise induced an increase in muscle [lactate] and a significant increase in plasma [lactate], which were worthy of further investigation. The similar swimming speed and biochemical indicators after exercise in the U crit and U cat groups at low acceleration rates suggested that U cat can be an alternative for the more frequently adopted protocols in U crit in Chinese bream and possibly in other cyprinid fish species.

Topics: Acceleration; Animals; Cyprinidae; Glucose; Glycogen; Hypoxia; Lactic Acid; Liver; Muscles; Oxygen; Swimming

Hepatic glucose production (HGP) normally begins just prior to birth. Prolonged fetal hypoglycemia, intrauterine growth restriction, and acute hypoxemia produce an early activation of fetal HGP. To test the hypothesis that prolonged hypoxemia increases factors which regulate HGP, studies were performed in fetuses that were bled to anemic conditions (anemic: n = 11) for 8.9 ± 0.4 days and compared with control fetuses (n = 7). Fetal arterial hematocrit and oxygen content were 32% and 50% lower, respectively, in anemic vs. controls (P < 0.005). Arterial plasma glucose was 15% higher in the anemic group (P < 0.05). Hepatic mRNA expression of phosphonenolpyruvate carboxykinase (PCK1) was twofold higher in the anemic group (P < 0.05). Arterial plasma glucagon concentrations were 70% higher in anemic fetuses compared with controls (P < 0.05), and they were positively associated with hepatic PCK1 mRNA expression (P < 0.05). Arterial plasma cortisol concentrations increased 90% in the anemic fetuses (P < 0.05), but fetal cortisol concentrations were not correlated with hepatic PCK1 mRNA expression. Hepatic glycogen content was 30% lower in anemic vs. control fetuses (P < 0.05) and was inversely correlated with fetal arterial plasma glucagon concentrations. In isolated primary fetal sheep hepatocytes, incubation in low oxygen (3%) increased PCK1 mRNA threefold compared with incubation in normal oxygen (21%). Together, these results demonstrate that glucagon and PCK1 may potentiate fetal HGP during chronic fetal anemic hypoxemia.

Topics: Anemia; Animals; Female; Fetal Hypoxia; Fetus; Glucagon; Glucose-6-Phosphatase; Glycogen; Hepatocytes; Hydrocortisone; Hypoxia; Liver; Organ Size; Phosphoenolpyruvate Carboxykinase (GTP); Pregnancy; RNA, Messenger; Sheep; Umbilical Cord

Mobilization of glycogen stores was examined in the anoxic crucian carp (Carassius carassius Linnaeus). Winter-acclimatized fish were exposed to anoxia for 1, 3, or 6 weeks at 2 °C, and changes in the size of glycogen deposits were followed. After 1 week of anoxia, a major part of the glycogen stores was mobilized in liver (79.5 %) and heart (75.6 %), and large decreases occurred in gill (46.7 %) and muscle (45.1 %). Brain was an exception in that its glycogen content remained unchanged. The amount of glycogen degraded during the first anoxic week was sufficient for the anaerobic ethanol production for more than 6 weeks of anoxia. After 3 and 6 weeks of anoxia, there was little further degradation of glycogen in other tissues except the brain where the stores were reduced by 30.1 and 49.9 % after 3 and 6 weeks of anoxia, respectively. One week of normoxic recovery following the 6-week anoxia was associated with a complete replenishment of the brain glycogen and partial recovery of liver, heart, and gill glycogen stores. Notably, the resynthesis of glycogen occurred at the expense of the existing energy reserves of the body in fasting fish. These findings indicate that in crucian carp, glycogen stores are quickly mobilized after the onset of anoxia, with the exception of the brain whose glycogen stores may be saved for putative emergency situations.

Topics: Acclimatization; Acetates; Ammonia; Animals; Body Weight; Brain; Carps; Ethanol; Gills; Glycogen; Heart; Hypoxia; Lactic Acid; Liver; Organ Size; Spleen

It is increasingly important to investigate the effect of temperature on hypoxia tolerance in fish species, as worldwide hypoxia worsens with increases in global warming. We selected the hypoxia-tolerant crucian carp (Carassius carassius) and the hypoxia-sensitive Chinese bream (Parabramis pekinensis) as model fish and investigated their hypoxia tolerance based on the critical oxygen tension of the routine metabolic rate (M˙O2rout) (Pcrit), aquatic surface respiration (ASRcrit) and loss of equilibrium (LOEcrit) after two weeks of acclimation at either 10, 20 or 30 °C. We also measured the tissue substrate (glycogen and glucose of muscle and liver) and lactate levels of both normoxia- and hypoxia-treated fish (post-LOE). Crucian carp exhibited significantly lower Pcrit and LOEcrit but not ASRcrit. Crucian carp possessed higher hypoxia tolerance, partially due to a higher tissue glycogen reserve, which provides cellular fuel under severe hypoxia, as well as higher lactate tolerance and clearance ability than Chinese bream. The hypoxia tolerance was maintained in crucian carp but was decreased in Chinese bream as the temperature increased. The difference between the two species is based on the greater recruitment of tissue glycogen, resulting in an increased level of cellular fuel during hypoxia in crucian carp than in Chinese bream. In addition, crucian carp possessed the greater liver lactate clearance capacity, and the smaller increase in the M˙O2rout at higher temperatures compared to Chinese bream. Furthermore, substrate shortage and decreased lactate tolerance at high temperatures in Chinese bream might also contribute to the difference in hypoxia tolerance between the two species.

Topics: Adaptation, Physiological; Animals; Brain; Cyprinidae; Glucose; Glycogen; Hypoxia; Lactic Acid; Liver; Muscles; Species Specificity; Temperature

The strategy for most teleost to survive in hypoxic or anoxic conditions is to conserve energy expenditure, which can be achieved by suppressing energy-consuming activities such as ion regulation. However, an air-breathing fish can cope with hypoxic stress using a similar adjustment or by enhancing gas exchange ability, both behaviorally and physiologically. This study examined Trichogaster lalius, an air-breathing fish without apparent gill modification, for their gill ion-regulatory abilities and glycogen utilization under a hypoxic treatment. We recorded air-breathing frequency, branchial morphology, and the expression of ion-regulatory proteins (Na(+)/K(+)-ATPase and vacuolar-type H(+)-ATPase) in the 1(st) and 4(th) gills and labyrinth organ (LO), and the expression of glycogen utilization (GP, glycogen phosphorylase protein expression and glycogen content) and other protein responses (catalase, CAT; carbonic anhydrase II, CAII; heat shock protein 70, HSP70; hypoxia-inducible factor-1α, HIF-1α; proliferating cell nuclear antigen, PCNA; superoxidase dismutase, SOD) in the gills of T. lalius after 3 days in hypoxic and restricted conditions. No morphological modification of the 1(st) and 4(th) gills was observed. The air-breathing behavior of the fish and CAII protein expression both increased under hypoxia. Ion-regulatory abilities were not suppressed in the hypoxic or restricted groups, but glycogen utilization was enhanced within the groups. The expression of HIF-1α, HSP70 and PCNA did not vary among the treatments. Regarding the antioxidant system, decreased CAT enzyme activity was observed among the groups. In conclusion, during hypoxic stress, T. lalius did not significantly reduce energy consumption but enhanced gas exchange ability and glycogen expenditure.

Topics: Air; Animals; Antioxidants; Aquatic Organisms; Carbonic Anhydrases; Catalase; Female; Gene Expression Regulation; Gills; Glycogen; Glycogen Phosphorylase; HSP70 Heat-Shock Proteins; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ions; Male; Oxygen; Perciformes; Proliferating Cell Nuclear Antigen; Respiration; RNA, Messenger; Sodium; Sodium-Potassium-Exchanging ATPase; Stress, Physiological; Superoxide Dismutase; Time Factors; Vacuolar Proton-Translocating ATPases

We examined the hypothesis that Trichogaster microlepis, a fish with an accessory air-breathing organ, uses a compensatory strategy involving changes in both behavior and protein levels to enhance its gas exchange ability. This compensatory strategy enables the gill ion-regulatory metabolism to maintain homeostasis during exposure to hypoxia. The present study aimed to determine whether ionic regulation, glycogen utilization and antioxidant activity differ in terms of expression under hypoxic stresses; fish were sampled after being subjected to 3 or 12h of hypoxia and 12h of recovery under normoxia. The air-breathing behavior of the fish increased under hypoxia. No morphological modification of the gills was observed. The expression of carbonic anhydrase II did not vary among the treatments. The Na(+)/K(+)-ATPase enzyme activity did not decrease, but increases in Na(+)/K(+)-ATPase protein expression and ionocyte levels were observed. The glycogen utilization increased under hypoxia as measured by glycogen phosphorylase protein expression and blood glucose level, whereas the glycogen content decreased. The enzyme activity of several components of the antioxidant system in the gills, including catalase, glutathione peroxidase, and superoxidase dismutase, increased in enzyme activity. Based on the above data, we concluded that T. microlepis is a hypoxia-tolerant species that does not exhibit ion-regulatory suppression but uses glycogen to maintain energy utilization in the gills under hypoxic stress. Components of the antioxidant system showed increased expression under the applied experimental treatments.

Topics: Air; Animal Structures; Animals; Antioxidants; Aquatic Organisms; Blood Glucose; Carbonic Anhydrases; Catalase; Female; Gene Expression Regulation; Gills; Glutathione Peroxidase; Glycogen; Glycogen Phosphorylase; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Ions; Liver; Male; Perciformes; Respiration; RNA, Messenger; Sodium-Potassium-Exchanging ATPase; Superoxide Dismutase

In the present study, the combined effects of hypoxia and nutritional status were examined in common carp (Cyprinus carpio), a relatively hypoxia tolerant cyprinid. Fish were either fed or fasted and were exposed to hypoxia (1.5-1.8mg O2L(-1)) at or slightly above their critical oxygen concentration during 1, 3 or 7days followed by a 7day recovery period. Ventilation initially increased during hypoxia, but fasted fish had lower ventilation frequencies than fed fish. In fed fish, ventilation returned to control levels during hypoxia, while in fasted fish recovery only occurred after reoxygenation. Due to this, C. carpio managed, at least in part, to maintain aerobic metabolism during hypoxia: muscle and plasma lactate levels remained relatively stable although they tended to be higher in fed fish (despite higher ventilation rates). However, during recovery, compensatory responses differed greatly between both feeding regimes: plasma lactate in fed fish increased with a simultaneous breakdown of liver glycogen indicating increased energy use, while fasted fish seemed to economize energy and recycle decreasing plasma lactate levels into increasing liver glycogen levels. Protein was used under both feeding regimes during hypoxia and subsequent recovery: protein levels reduced mainly in liver for fed fish and in muscle for fasted fish. Overall, nutritional status had a greater impact on energy reserves than the lack of oxygen with a lower hepatosomatic index and lower glycogen stores in fasted fish. Fasted fish transiently increased Na(+)/K(+)-ATPase activity under hypoxia, but in general ionoregulatory balance proved to be only slightly disturbed, showing that sufficient energy was left for ion regulation.

Topics: Ammonia; Animals; Carps; Energy Metabolism; Fasting; Feeding Behavior; Gills; Glycogen; Hypoxia; Ions; Lactic Acid; Lipid Metabolism; Liver; Muscles; Nutritional Status; Proteins; Respiration; Sodium-Potassium-Exchanging ATPase

To what extent hypoxia alters the adenosine (ADO) system and impacts on cardiac function during embryogenesis is not known. Ectonucleoside triphosphate diphosphohydrolase (CD39), ecto-5'-nucleotidase (CD73), adenosine kinase (AdK), adenosine deaminase (ADA), equilibrative (ENT1,3,4), and concentrative (CNT3) transporters and ADO receptors A1, A2A, A2B, and A3 constitute the adenosinergic system. During the first 4 days of development chick embryos were exposed in ovo to normoxia followed or not followed by 6 h hypoxia. ADO and glycogen content and mRNA expression of the genes were determined in the atria, ventricle, and outflow tract of the normoxic (N) and hypoxic (H) hearts. Electrocardiogram and ventricular shortening of the N and H hearts were recorded ex vivo throughout anoxia/reoxygenation ± ADO. Under basal conditions, CD39, CD73, ADK, ADA, ENT1,3,4, CNT3, and ADO receptors were differentially expressed in the atria, ventricle, and outflow tract. In H hearts ADO level doubled, glycogen decreased, and mRNA expression of all the investigated genes was downregulated by hypoxia, except for A2A and A3 receptors. The most rapid and marked downregulation was found for ADA in atria. H hearts were arrhythmic and more vulnerable to anoxia-reoxygenation than N hearts. Despite downregulation of the genes, exposure of isolated hearts to ADO 1) preserved glycogen through activation of A1 receptor and Akt-GSK3β-GS pathway, 2) prolonged activity and improved conduction under anoxia, and 3) restored QT interval in H hearts. Thus hypoxia-induced downregulation of the adenosinergic system can be regarded as a coping response, limiting the detrimental accumulation of ADO without interfering with ADO signaling.

Topics: 5'-Nucleotidase; Adaptation, Physiological; Adenosine; Adenosine Kinase; Animals; Antigens, CD; Apyrase; Chick Embryo; Energy Metabolism; Equilibrative Nucleoside Transport Proteins; Gene Expression Regulation, Developmental; Glycogen; Glycogen Synthase; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Heart; Hypoxia; Membrane Transport Proteins; Myocardium; Organogenesis; Proto-Oncogene Proteins c-akt; Receptors, Purinergic P1; RNA, Messenger; Signal Transduction; Time Factors

Periods of oxygen deprivation can lead to ion and water imbalances in affected tissues that manifest as swelling (edema). Although oxygen deprivation-induced edema is a major contributor to injury in clinical ischemic diseases such as heart attack and stroke, the pathophysiology of this process is incompletely understood. In the present study we investigate the impact of aquaporin-mediated water transport on survival in a Caenorhabditis elegans model of edema formation during complete oxygen deprivation (anoxia). We find that nematodes lacking aquaporin water channels in tissues that interface with the surrounding environment display decreased edema formation and improved survival rates in anoxia. We also find that these animals have significantly reduced demand for glycogen as an energetic substrate during anoxia. Together, our data suggest that reductions in membrane water permeability may be sufficient to induce a hypometabolic state during oxygen deprivation that reduces injury and extends survival limits.

Topics: Adaptation, Physiological; Animals; Aquaporin 2; Aquaporin 4; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Edema; Energy Metabolism; Genotype; Glycogen; Hypoxia; Osmotic Pressure; Phenotype; Stress, Psychological; Time Factors; Water-Electrolyte Balance

Ischemic tissue is an environment with limited oxygen and nutrition availability. The poor retention of mesenchymal stem cells (MSC) in ischemic tissues greatly limits their therapeutic potential. The aim of this study was to determine whether and how inducible metabolic adaptation enhances MSC survival and therapy under ischemia.. MSC were subjected to glycogen synthase 1-specific small interfering RNA or vehicle treatment, and then sublethal hypoxic preconditioning (HP) was applied to induce glycogenesis. The treated cells were subjected to ischemic challenge. The results exhibited that HP of MSC induced glycogen storage and stimulated glycogen catabolism and cellular ATP production, thereby preserving cell viability in long-term ischemia. In vivo study using the mouse limb ischemia model transplanted with HP or control MSC into the ischemic thigh muscles revealed a significant increased retention of MSC with glycogen storage associated with improved limb salvage, perfusion recovery and angiogenesis in the ischemic muscles. In contrast, glycogen synthesis inhibition significantly abolished these improvements. Further molecular analysis indicated that phosphoinositide 3-kinase/AKT, hypoxia-inducible factor-1, and glycogen synthase kinase-3β regulated expression of glycogenesis genes, including glucose transporter 1, hexokinase, phosphoglucomutase 1, glycogen synthase 1, and glycogen phosphorylase, thereby regulating glycogen metabolism of stem cell during HP.. HP-induced glycogen storage improves MSC survival and therapy in ischemic tissues. Thus, inducible metabolic adaptation in stem cells may be considered as a novel strategy for potentiating stem cell therapy for ischemia.

Topics: Adaptation, Physiological; Adenosine Triphosphate; Animals; Cell Survival; Cells, Cultured; Disease Models, Animal; Energy Metabolism; Gene Expression Regulation, Enzymologic; Glycogen; Glycogen Synthase; Hindlimb; Hypoxia; Ischemia; Male; Mesenchymal Stem Cell Transplantation; Mesenchymal Stem Cells; Mice; Mice, Inbred C57BL; Muscle, Skeletal; Neovascularization, Physiologic; Recovery of Function; Regional Blood Flow; RNA Interference; Signal Transduction; Time Factors; Transfection

Previous studies have shown evidence of genomic incompatibility and mitochondrial enzyme dysfunction in hybrids of bluegill (Lepomis macrochirus Rafinesque) and pumpkinseed (Lepomis gibbosus Linnaeus) sunfish (Davies et al., 2012 Physiol. Biochem. Zool. 85, 321-331). We assessed if these differences in mitochondria had an impact on metabolic processes that depend on mitochondrial function, specifically hypoxia tolerance and recovery from burst exercise. Bluegill, pumpkinseed, and their hybrids showed no difference in the critical oxygen tension (Pcrit) and no differences in tissue metabolites measured after exposure to 10% O₂ for 30min. In contrast, loss of equilibrium (LOE) measurements showed that hybrids had reduced hypoxia tolerance and lacked the size-dependence in hypoxia tolerance seen in the parental species. However, we found no evidence of systematic differences in metabolite levels in fish after LOE. Furthermore, there were abundant glycogen reserves at the point of loss of equilibrium. The three genotypes did not differ in metabolite status at rest, showed an equal disruption at exhaustion, and similar metabolic profiles throughout recovery. Thus, we found no evidence of a mitochondria dysfunction in hybrids, and mitochondrial differences and oxidative metabolism did not explain the variation in hypoxia tolerance seen in the hybrid and two parental species.

Topics: Allostasis; Animals; Behavior, Animal; Brain; Crosses, Genetic; Female; Genome, Mitochondrial; Glycogen; Hybridization, Genetic; Hypoxia; Lakes; Male; Mitochondria; Motor Activity; Muscle Fibers, Fast-Twitch; Myocardium; Ontario; Oxidative Phosphorylation; Perciformes; Species Specificity

In this study, we compared the effect of sprint interval training (SIT) in normoxia versus hypoxia on muscle glycolytic and oxidative capacity, monocarboxylate transporter content, and endurance exercise performance.. Healthy male volunteers (18-30 yr) performed 6 wk of SIT on a cycling ergometer (30-s sprints vs 4.5-min rest intervals; 3 d · wk(-1)) in either normobaric hypoxia (HYP, FiO2 = 14.4%, n = 10) or normoxia (NOR, FiO2 = 20.9%, n = 9). The control group did not train (CON, n = 10). Training load was increased from four sprints per session in week 1 to nine sprints in week 6. Before and after SIT, subjects performed a maximal incremental exercise test plus a 10-min simulated time trial on a cycle ergometer in both normoxia (MAX nor and TT nor) and hypoxia (MAX hyp and TT hyp). A needle biopsy was taken from musculus vastus lateralis at rest 5-6 d after the last exercise session.. SIT increased muscle phosphofructokinase activity more in HYP (+59%, P < 0.05) than that in NOR (+17%), whereas citrate synthase activity was similar between groups. Compared with the pretest, power outputs corresponding to 4 mmol blood lactate in HYP during MAX nor (+7%) and MAX hyp (+9%) were slightly increased (P < 0.05), whereas values were constant in NOR. V·O 2max in MAX nor and TT performance in TT nor and TT hyp were increased by ≈ 6%-8% (P < 0.05) in either group. The training elevated monocarboxylate transporter 1 protein content by ≈ 70% (P < 0.05). In CON, all measurements were constant throughout the study.. SIT in hypoxia up-regulated muscle phosphofructokinase activity and the anaerobic threshold more than SIT in normoxia but did not enhance endurance exercise performance.

Topics: Adolescent; Adult; Anaerobic Threshold; Bicycling; Citrate (si)-Synthase; Exercise Test; Glycogen; Humans; Hypoxia; Male; Monocarboxylic Acid Transporters; Muscle Proteins; Oxygen Consumption; Phosphofructokinases; Physical Conditioning, Human; Physical Endurance; Quadriceps Muscle; Symporters; Young Adult

Provision of supplemental oxygen to maintain soft tissue viability acutely following trauma in which vascularization has been compromised would be beneficial for limb and tissue salvage. For this application, an oxygen generating biomaterial that may be injected directly into the soft tissue could provide an unprecedented treatment in the acute trauma setting. The purpose of the current investigation was to determine if sodium percarbonate (SPO), an oxygen generating biomaterial, is capable of maintaining resting skeletal muscle homeostasis under otherwise hypoxic conditions. In the current studies, a biologically and physiologically compatible range of SPO (1-2 mg/mL) was shown to: 1) improve the maintenance of contractility and attenuate the accumulation of HIF1α, depletion of intramuscular glycogen, and oxidative stress (lipid peroxidation) that occurred following ∼30 minutes of hypoxia in primarily resting (duty cycle = 0.2 s train/120 s contraction interval <0.002) rat extensor digitorum longus (EDL) muscles in vitro (95% N2-5% CO2, 37°C); 2) attenuate elevations of rat EDL muscle resting tension that occurred during contractile fatigue testing (3 bouts of 25 100 Hz tetanic contractions; duty cycle = 0.2 s/2 s = 0.1) under oxygenated conditions in vitro (95% O2-5% CO2, 37°C); and 3) improve the maintenance of contractility (in vivo) and prevent glycogen depletion in rat tibialis anterior (TA) muscle in a hindlimb ischemia model (i.e., ligation of the iliac artery). Additionally, injection of a commercially available lipid oxygen-carrying compound or the components (sodium bicarbonate and hydrogen peroxide) of 1 mg/mL SPO did not improve EDL muscle contractility under hypoxic conditions in vitro. Collectively, these findings demonstrate that a biological and physiological concentration of SPO (1-2 mg/mL) injected directly into rat skeletal muscle (EDL or TA muscles) can partially preserve resting skeletal muscle homeostasis under hypoxic conditions.

Topics: Animals; Female; Glycogen; Homeostasis; Hypoxia; Ischemia; Lipid Peroxidation; Muscle, Skeletal; Rats, Inbred Lew

Diabetic nephropathy is strongly associated with both increased oxidative stress and kidney tissue hypoxia. The increased oxidative stress causes increased kidney oxygen consumption resulting in kidney tissue hypoxia. To date, it has been difficult to determine the role of kidney hypoxia, per se, for the development of nephropathy. We tested the hypothesis that kidney hypoxia, without confounding factors such as hyperglycemia or elevated oxidative stress, results in nephropathy. To induce kidney hypoxia, dinitrophenol (30 mg per day per kg bodyweight by gavage), a mitochondrial uncoupler that increases oxygen consumption and causes kidney hypoxia, was administered for 30 consecutive days to rats. Thereafter, glomerular filtration rate, renal blood flow, kidney oxygen consumption, kidney oxygen tension, kidney concentrations of glucose and glycogen, markers of oxidative stress, urinary protein excretion, and histological findings were determined and compared with vehicle-treated controls. Dinitrophenol did not affect arterial blood pressure, renal blood flow, glomerular filtration rate, blood glucose, or markers of oxidative stress but increased kidney oxygen consumption, and reduced cortical and medullary concentrations of glucose and glycogen, and resulted in intrarenal tissue hypoxia. Furthermore, dinitrophenol treatment increased urinary protein excretion, kidney vimentin expression, and infiltration of inflammatory cells. In conclusion, increased mitochondrial oxygen consumption results in kidney hypoxia and subsequent nephropathy. Importantly, these results demonstrate that kidney tissue hypoxia, per se, without confounding hyperglycemia or oxidative stress, may be sufficient to initiate the development of nephropathy and therefore demonstrate a new interventional target for treating kidney disease.

Topics: Animals; Dinitrophenols; Glucose; Glycogen; Hyperglycemia; Hypoxia; Kidney; Kidney Diseases; Male; Mitochondria; Oxidative Stress; Oxygen Consumption; Rats; Rats, Sprague-Dawley; Renal Circulation; Uncoupling Agents; Vimentin

It is already known that the New Zealand snapper (Pagrus auratus, Sparidae) does not avoid hypoxia until reaching an oxygen partial pressure (PO(2)) of 3.1±1.2 kPa at 18 °C. Avoidance at this level of PO(2) and temperature is below the critical oxygen partial pressure of the species (P(crit)=5.8±0.6 kPa, 43.5±4.5 mmHg) and is therefore expected to result in major physiological stress. Results from the current study showed that avoidance was associated with numerous physiological perturbations, including a significant endocrine response, haematological changes, osmoregulatory disturbance and metabolic adjustments in the heart, liver and muscle. Snapper clearly experienced physiological stress at the point of avoidance but they were not however in a state of physiological exhaustion since some fuel reserves were still available. In addition to avoidance, snapper also showed a subtle reduction in swimming speed - this energy-saving response may have helped snapper minimise the physiological challenge of low O(2) residence. It is therefore concluded that snapper can reside in water below their P(crit) threshold for brief periods of time and, without any evidence of physiological exhaustion at the point of avoidance, fish should recover quickly once normoxia is selected. Lastly, with signs of anaerobic metabolism in cardiac tissue at the point of avoidance, we tentatively suggest that snapper may leave hypoxia to protect heart function.

Topics: Animals; Basal Metabolism; Behavior, Animal; Blood Glucose; Glycogen; Hematocrit; Hydrocortisone; Hypoxia; Lactic Acid; Liver; Muscles; Myocardium; Oxygen Consumption; Perciformes; Swimming

The present study was aimed to explore the changes of phosphorylated AMP-activated protein kinase (pAMPK) level in skeletal muscle after exposure to acute hypobaric hypoxia and exhaustive exercise. Thirty-two male Sprague-Dawley (SD) rats were randomly divided into sea level and high altitude groups. The rats in high altitude group were submitted to simulated 5 000 m of high altitude in a hypobaric chamber for 24 h, and sea level group was maintained at normal conditions. All the rats were subjected to exhaustive swimming exercise. The exhaustion time was recorded. Before and after the exercise, blood lactate and glycogen content in skeletal muscle were determined; AMPK and pAMPK levels in skeletal muscle were detected by Western blot. The results showed that the exhaustion time was significantly decreased after exposure to high altitude. At the moment of exhaustion, high altitude group had lower blood lactate concentration and higher surplus glycogen content in gastrocnemius compared with sea level group. Exhaustive exercise significantly increased the pAMPK/AMPK ratio in rat skeletal muscles from both sea level and high altitude groups. However, high altitude group showed lower pAMPK/AMPK ratio after exhaustion compared to sea level group. These results suggest that, after exposure to acute hypobaric hypoxia, the decrement in exercise capacity may not be due to running out of glycogen, accumulation of lactate or disturbance in energy status in skeletal muscle.

Topics: Altitude; AMP-Activated Protein Kinases; Animals; Computer Simulation; Glycogen; Hypoxia; Lactic Acid; Male; Motor Activity; Muscle, Skeletal; Phosphorylation; Physical Exertion; Rats; Rats, Sprague-Dawley

To elucidate the role of glycogen in the contraction of tracheal smooth muscle, we investigated the changes in the glycogen contents of the bovine trachea during contractions induced by high K(+) and hypoxia (achieved by bubbling N(2) instead of O(2)), either in a glucose-free condition or in the presence of iodoacetic acid (IAA), an inhibitor of glycolysis. Hyperosmotic addition of 65 mM KCl (H-65 K(+)) induced a sustained contraction. A glucose-free condition did not affect H-65 K(+)-induced contraction. However, hypoxia slightly inhibited the contraction, and glucose-free PSS with hypoxia or IAA remarkably inhibited the H-65 K(+)-induced contraction. H-65 K(+) induced a sustained increase in reduced pyridine nucleotide (PNred) fluorescence, representing glycolysis activity. Hypoxia alone slightly enhanced PNred fluorescence, and when combined with a glucose-free condition, it remarkably enhanced the H-65 K(+)-induced PNred fluorescence. IAA inhibited PNred fluorescence. In the presence of H-65 K(+), a glucose-free condition, hypoxia and the combination of glucose-free PSS and hypoxia decreased the glycogen contents. However, IAA had no effect on glycogen contents. Although hypoxia or glucose-free PSS did not affect PCr and ATP contents, the combination of hypoxia and glucose-free PSS or IAA induced a gradual decrease of PCr content. In conclusion, we suggest that endogenous glycogen was utilized to increase the activity of glycolysis for maintaining high K(+)-induced contraction of the bovine trachea in the glucose -free and/or hypoxic condition.

Topics: Adenosine Triphosphate; Animals; Cattle; Female; Glycogen; Glycolysis; Hypoxia; In Vitro Techniques; Male; Microscopy, Fluorescence; Muscle Contraction; Muscle, Smooth; Phosphocreatine; Potassium Chloride; Trachea

Fatty acid (FA) metabolism plays a central role in body homeostasis and related diseases. Thus, FA metabolic enzymes are attractive targets for drug therapy. Mouse studies on Acetyl-coenzymeA-carboxylase (ACC), the rate-limiting enzyme for FA synthesis, have highlighted its homeostatic role in liver and adipose tissue. We took advantage of the powerful genetics of Drosophila melanogaster to investigate the role of the unique Drosophila ACC homologue in the fat body and the oenocytes. The fat body accomplishes hepatic and storage functions, whereas the oenocytes are proposed to produce the cuticular lipids and to contribute to the hepatic function. RNA-interfering disruption of ACC in the fat body does not affect viability but does result in a dramatic reduction in triglyceride storage and a concurrent increase in glycogen accumulation. These metabolic perturbations further highlight the role of triglyceride and glycogen storage in controlling circulatory sugar levels, thereby validating Drosophila as a relevant model to explore the tissue-specific function of FA metabolic enzymes. In contrast, ACC disruption in the oenocytes through RNA-interference or tissue-targeted mutation induces lethality, as does oenocyte ablation. Surprisingly, this lethality is associated with a failure in the watertightness of the spiracles-the organs controlling the entry of air into the trachea. At the cellular level, we have observed that, in defective spiracles, lipids fail to transfer from the spiracular gland to the point of air entry. This phenotype is caused by disrupted synthesis of a putative very-long-chain-FA (VLCFA) within the oenocytes, which ultimately results in a lethal anoxic issue. Preventing liquid entry into respiratory systems is a universal issue for air-breathing animals. Here, we have shown that, in Drosophila, this process is controlled by a putative VLCFA produced within the oenocytes.

Topics: Acetyl-CoA Carboxylase; Animals; Carbohydrate Metabolism; Drosophila melanogaster; Fat Body; Fatty Acids; Glycogen; Hypoxia; Lipid Metabolism; Respiratory System; RNA Interference; Triglycerides; Water

People living at high altitude appear to have lower blood glucose levels and decreased incidence of diabetes. Faster glucose uptake and increased insulin sensitivity are likely explanations for these findings: skeletal muscle is the largest glucose sink in the body, and its adaptation to the hypoxia of altitude may influence glucose uptake and insulin sensitivity. This study tested the hypothesis that chronic normobaric hypoxia increases insulin-stimulated glucose uptake in soleus muscles and decreases plasma glucose levels. Adult male C57BL/6J mice were kept in normoxia [fraction of inspired O₂ = 21% (Control)] or normobaric hypoxia [fraction of inspired O₂ = 10% (Hypoxia)] for 4 wk. Then blood glucose and insulin levels, in vitro muscle glucose uptake, and indexes of insulin signaling were measured. Chronic hypoxia lowered blood glucose and plasma insulin [glucose: 14.3 ± 0.65 mM in Control vs. 9.9 ± 0.83 mM in Hypoxia (P < 0.001); insulin: 1.2 ± 0.2 ng/ml in Control vs. 0.7 ± 0.1 ng/ml in Hypoxia (P < 0.05)] and increased insulin sensitivity determined by homeostatic model assessment 2 [21.5 ± 3.8 in Control vs. 39.3 ± 5.7 in Hypoxia (P < 0.03)]. There was no significant difference in basal glucose uptake in vitro in soleus muscle (1.59 ± 0.24 and 1.71 ± 0.15 μmol·g⁻¹·h⁻¹ in Control and Hypoxia, respectively). However, insulin-stimulated glucose uptake was 30% higher in the soleus after 4 wk of hypoxia than Control (6.24 ± 0.23 vs. 4.87 ± 0.37 μmol·g⁻¹·h⁻¹, P < 0.02). Muscle glycogen content was not significantly different between the two groups. Levels of glucose transporters 4 and 1, phosphoinositide 3-kinase, glycogen synthase kinase 3, protein kinase B/Akt, and AMP-activated protein kinase were not affected by chronic hypoxia. Akt phosphorylation following insulin stimulation in soleus muscle was significantly (25%) higher in Hypoxia than Control (P < 0.05). Neither glycogen synthase kinase 3 nor AMP-activated protein kinase phosphorylation changed after 4 wk of hypoxia. These results demonstrate that the adaptation of skeletal muscles to chronic hypoxia includes increased insulin-stimulated glucose uptake.

Topics: Altitude; AMP-Activated Protein Kinase Kinases; Animals; Blood Glucose; Body Weight; Glucose; Glycogen; Hematocrit; Hypoglycemic Agents; Hypoxia; Insulin; Male; Mice; Mice, Inbred C57BL; Models, Animal; Muscle, Skeletal; Protein Kinases; Proto-Oncogene Proteins c-akt

It is not known how the Pacific hagfish (Eptatretus stoutii) can survive extended periods of anoxia. The present study used two experimental approaches to examine energy use during and following anoxic exposure periods of different durations (6, 24 and 36 h). By measuring oxygen consumption prior to anoxic exposure, we detected a circadian rhythm, with hagfish being active during night and showing a minimum routine oxygen consumption (RMR) during the daytime. By measuring the excess post-anoxic oxygen consumption (EPAOC) after 6 and 24 h it was possible to mathematically account for RMR being maintained even though heme stores of oxygen would have been depleted by the animal's metabolism during the first hours of anoxia. However, EPAOC after 36 h of anoxia could not account for RMR being maintained. Measurements of tissue glycogen disappearance and lactate appearance during anoxia showed that the degree of glycolysis and the timing of its activation varied among tissues. Yet, neither measurement could account for the RMR being maintained during even the 6-h anoxic period. Therefore, two independent analyses of the metabolic responses of hagfish to anoxia exposure suggest that hagfish utilize metabolic rate suppression as part of the strategy for longer-term anoxia survival.

Topics: Adenosine Triphosphate; Animals; Basal Metabolism; Glucose; Glycogen; Hagfishes; Hypoxia; Lactic Acid; Liver; Muscle, Skeletal; Myocardium; Oxygen Consumption; Phosphocreatine; Respiration; Tongue

The ability of the developing myocardium to tolerate oxidative stress during early gestation is an important issue with regard to possible detrimental consequences for the fetus. In the embryonic heart, antioxidant defences are low, whereas glycolytic flux is high. The pro- and antioxidant mechanisms and their dependency on glucose metabolism remain to be explored. Isolated hearts of 4-day-old chick embryos were exposed to normoxia (30 min), anoxia (30 min), and hyperoxic reoxygenation (60 min). The time course of ROS production in the whole heart and in the atria, ventricle, and outflow tract was established using lucigenin-enhanced chemiluminescence. Cardiac rhythm, conduction, and arrhythmias were determined. The activity of superoxide dismutase, catalase, gutathione reductase, and glutathione peroxidase as well as the content of reduced and oxidized glutathione were measured. The relative contribution of the ROS-generating systems was assessed by inhibition of mitochondrial complexes I and III (rotenone and myxothiazol), NADPH oxidases (diphenylene iodonium and apocynine), and nitric oxide synthases (N-monomethyl-L-arginine and N-iminoethyl-L-ornithine). The effects of glycolysis inhibition (iodoacetate), glucose deprivation, glycogen depletion, and lactate accumulation were also investigated. In untreated hearts, ROS production peaked at 10.8 ± 3.3, 9 ± 0.8, and 4.8 ± 0.4 min (means ± SD; n = 4) of reoxygenation in the atria, ventricle, and outflow tract, respectively, and was associated with arrhythmias. Functional recovery was complete after 30-40 min. At reoxygenation, 1) the respiratory chain and NADPH oxidases were the main sources of ROS in the atria and outflow tract, respectively; 2) glucose deprivation decreased, whereas glycogen depletion increased, oxidative stress; 3) lactate worsened oxidant stress via NADPH oxidase activation; 4) glycolysis blockade enhanced ROS production; 5) no nitrosative stress was detectable; and 6) the glutathione redox cycle appeared to be a major antioxidant system. Thus, the glycolytic pathway plays a predominant role in reoxygenation-induced oxidative stress during early cardiogenesis. The relative contribution of mitochondria and extramitochondrial systems to ROS generation varies from one region to another and throughout reoxygenation.

Topics: Animals; Chick Embryo; Electron Transport Complex I; Electron Transport Complex III; Glycogen; Glycolysis; Heart; Hypoxia; Iodoacetates; Lactates; Methacrylates; Mitochondria, Heart; Myocardium; NADPH Oxidases; NG-Nitroarginine Methyl Ester; Ornithine; Oxidative Stress; Reactive Oxygen Species; Reperfusion Injury; Rotenone; Thiazoles

Glycogen is a vital energy substrate for anaerobic organisms, and the size of glycogen stores can be a limiting factor for anoxia tolerance of animals. To this end, glycogen stores in 12 different tissues of the crucian carp (Carassius carassius L.), an anoxia-tolerant fish species, were examined. Glycogen content of different tissues was 2-10 times higher in winter (0.68-18.20% of tissue wet weight) than in summer (0.12-4.23%). In scale, bone and brain glycogen stores were strongly dependent on body mass (range between 0.6 and 785 g), small fish having significantly more glycogen than large fish (p < 0.05). In fin and skin, size dependence was evident in winter, but not in summer, while in other tissues (ventricle, atrium, intestine, liver, muscle, and spleen), no size dependence was found. The liver was much bigger in small than large fish (p < 0.001), and there was a prominent enlargement of the liver in winter irrespective of fish size. As a consequence, the whole body glycogen reserves, measured as a sum of glycogen from different tissues, varied from 6.1% of the body mass in the 1-g fish to 2.0% in the 800-g fish. Since anaerobic metabolic rate scales down with body size, the whole body glycogen reserves could provide energy for approximately 79 and 88 days of anoxia in small and large fish, respectively. There was, however, a drastic difference in tissue distribution of glycogen between large and small fish: in the small fish, the liver was the major glycogen store (68% of the stores), while in the large fish, the white myotomal muscle was the principal deposit of glycogen (57%). Since muscle glycogen is considered to be unavailable for blood glucose regulation, its usefulness in anoxia tolerance of the large crucian carp might be limited, although not excluded. Therefore, mobilization of muscle glycogen under anoxia needs to be rigorously tested.

Topics: Animals; Body Size; Carps; Glycogen; Hypoxia; Liver; Muscles; Organ Size; Seasons

Past studies have suggested that the stress-induced GLUT4 localization pathway is damaged in fast-twitch muscles (white muscles) of obese subjects. In this study, we used obese rodents in an attempt to determine whether the stress-induced GLUT4 localization pathway is abnormal in slow-twitch muscles (red muscles), which are responsible for most daily activities. Protein expression levels of the intracellular stress sensor AMP-activated protein kinase (AMPK), its upstream kinase LKB1, its downstream protein AS160 and the glucose transporter protein 4 (GLUT4) in the red gastrocnemius muscle were measured under either resting or stress conditions (1 h of swimming or 14% hypoxia) in both lean and obese Zucker rats (n = 7 for each group). At rest, obese rats displayed higher fasting plasma insulin levels and increased muscle AMPK and AS160 phosphorylation levels compared with lean controls. No significant difference was found in the protein levels of LKB1, total GLUT4, or membrane GLUT4 between the obese and lean control groups. After one hour of swimming, AMPK and AS160 phosphorylation levels and the amount of GLUT4 translocated to the plasma membrane were significantly elevated in lean rats but remained unchanged in obese rats relative to their resting conditions. One hour 14% hypoxia did not cause significant changes in the LKB1-AMPK-AS160-GLUT4 pathway in either lean or obese rats. This study demonstrated that the AMPK-AS160-GLUT4 pathway was altered at basal levels and after exercise stimulation in the slow-twitch muscle of obese Zucker rats.

Topics: Adenylate Kinase; AMP-Activated Protein Kinase Kinases; Animals; Blood Glucose; Body Weight; Glucose Transporter Type 4; Glycogen; GTPase-Activating Proteins; Hypoxia; Insulin; Male; Muscle Fibers, Slow-Twitch; Obesity; Phosphorylation; Physical Exertion; Protein Serine-Threonine Kinases; Protein Transport; Rats; Rats, Zucker; Stress, Physiological

Rhodiola algida, Saussurea involucrata, and other herbs grown in Qinghai-Tibetan plateau have long been used to prevent and treat acute mountain sickness.. To screen and identify the anti-hypoxic constituents in the herbs grown in Qinghai-Tibetan plateau of Northwestern China.. The anti-hypoxic activities of 20 selected plateau herbs were examined against two positive controls, Rhodiola algida and acetazolamide, using the normobaric hypoxia model of mice. The herb with the highest activity was successively extracted with 70% ethanol, petroleum ether, chloroform, ethyl acetate and n-butanol. The extract with the highest activity was identified by comparing the survival time of mice under normobaric hypoxia condition after being subjected to different extracts. The identified extract was further tested by simulating high altitudes through an acute decompression model and a chronic decompression model for mice.. The herb found to have the highest anti-hypoxic activity was Saussurea involucrate (Kar. et Kir.) Sch.-Bip, and the most effective fraction was in the petroleum ether extract. Administration of petroleum ether extract of Saussurea involucrata (PESI) to mice at 50mg/kg significantly decreased the mortality of animals under acute decompression conditions. Changes in biochemical indicators for glycometabolism and energy metabolism, including adenosine triphosphate (ATP) content and adenosine triphosphatase (ATPase) activity in brain and cardiac muscle, lactic acid (LAC) and lactate dehydrogenase (LDH) in blood and cardiac muscles, blood sugar, and glycogen content in liver and skeletal muscle were reversed under chronic decompression conditions.. Saussurea involucrata (Kar. et Kir.) Sch.-Bip exhibits high anti-hypoxic activity that may be effective in preventing acute mountain sickness, and the active constituents are mainly in the petroleum ether extract.

Topics: Adenosine Triphosphate; Alkanes; Altitude Sickness; Animals; Blood Glucose; Brain; Ca(2+) Mg(2+)-ATPase; Decompression; Disease Models, Animal; Dose-Response Relationship, Drug; Energy Metabolism; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lactic Acid; Liver; Male; Mice; Mice, Inbred BALB C; Muscle, Skeletal; Myocardium; Plant Extracts; Plants, Medicinal; Saussurea; Sodium-Potassium-Exchanging ATPase; Solvents; Time Factors

We present evidence that oxygen consumption (VO2) is oxygen partial pressure (PO2)dependent in striated muscles and PO2-independent in the vasculature in representatives of three craniate taxa: two teleost fish, a hagfish and a rat. Blood vessel VO2 displayed varying degrees of independence in a PO2 range of 15-95 mmHg, while VO2 by striated muscle tissue slices from all species related linearly to PO2 between 0 and 125 mmHg, despite VO2 rates varying greatly between species and muscle type. In salmon red muscle, lactate concentrations fell in slices incubated at a PO2 of either 30 or 100 mmHg, suggesting aerobic rather than anaerobic metabolism. Consistent with this finding, potential energy, a proxy of ATP turnover, was PO2-dependent. Our data suggest that the reduction in VO2 with falling PO2 results in a decrease in ATP demand, suggesting that the hypoxic signal is sensed and cellular changes effected. Viability and diffusion limitation of the preparations were investigated using salmon cardiac and skeletal muscles. Following the initial PO2 depletion, reoxygenation of the Ringer bathing salmon cardiac muscle resulted in VO2S that was unchanged from the first run. VO2 increased in all muscles uncoupled with p-trifluoromethoxylphenyl-hydrazone (FCCP) and 2,4-dinitrophenol (DNP). Mitochondrial succinate dehydrogenase activity, quantified by reduction of 3-(4,5-dimethylthiazol)-2,5-diphenyl-2H-tetrazolium bromide (MTT) to formazan, was constant over the course of the experiment. These three findings indicate that the tissues remained viable over time and ruled out diffusion-limitation as a constraint on VO2.

Topics: 2,4-Dinitrophenol; Animals; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Energy Metabolism; Female; Glycogen; Hagfishes; Heme; Hypoxia; Liver; Male; Mitochondria, Muscle; Muscles; Myoglobin; Oxygen; Oxygen Consumption; Partial Pressure; Perciformes; Rats; Salmon; Succinate Dehydrogenase

When oxygen becomes limiting, cells reduce mitochondrial respiration and increase ATP production through anaerobic fermentation of glucose. The Hypoxia Inducible Factors (HIFs) play a key role in this metabolic shift by regulating the transcription of key enzymes of glucose metabolism. Here we show that oxygen regulates the expression of the muscle glycogen synthase (GYS1). Hypoxic GYS1 induction requires HIF activity and a Hypoxia Response Element within its promoter. GYS1 gene induction correlated with a significant increase in glycogen synthase activity and glycogen accumulation in cells exposed to hypoxia. Significantly, knockdown of either HIF1alpha or GYS1 attenuated hypoxia-induced glycogen accumulation, while GYS1 overexpression was sufficient to mimic this effect. Altogether, these results indicate that GYS1 regulation by HIF plays a central role in the hypoxic accumulation of glycogen. Importantly, we found that hypoxia also upregulates the expression of UTP:glucose-1-phosphate urydylyltransferase (UGP2) and 1,4-alpha glucan branching enzyme (GBE1), two enzymes involved in the biosynthesis of glycogen. Therefore, hypoxia regulates almost all the enzymes involved in glycogen metabolism in a coordinated fashion, leading to its accumulation. Finally, we demonstrated that abrogation of glycogen synthesis, by knock-down of GYS1 expression, impairs hypoxic preconditioning, suggesting a physiological role for the glycogen accumulated during chronic hypoxia. In summary, our results uncover a novel effect of hypoxia on glucose metabolism, further supporting the central importance of metabolic reprogramming in the cellular adaptation to hypoxia.

Topics: 1,4-alpha-Glucan Branching Enzyme; Animals; Gene Expression Regulation; Gene Expression Regulation, Enzymologic; Genes, Reporter; Glycogen; Glycogen Synthase; Humans; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Mice; Models, Biological; Muscles; Promoter Regions, Genetic; Response Elements; RNA Interference; UTP-Glucose-1-Phosphate Uridylyltransferase

Although enhanced biological phosphorus removal processes (EBPR) are popular methods for nutrient control, unstable treatment performances of full-scale systems are still not well understood. In this study, the interaction between electron acceptors present at the start of the anaerobic phase of an EBPR system and the amount of organic acids generated from simple substrate (rbsCOD) was investigated in a full-scale wastewater treatment plant. Quantification of microbial groups including phosphorus-accumulating microorganisms (PAOs), denitrifying PAOs (DPAOs), glycogen-accumulating microorganisms (GAOs) and ordinary heterotrophic microorganisms (OHOs) was based on a modified dynamic model. The intracellular phosphorus content of PAOs was also determined by the execution of mass balances for the biological stages of the plant. The EBPR activities observed in the plant and in batch tests (under idealized conditions) were compared with each other statistically as well. Modelling efforts indicated that the use of absolute anaerobic reaction (eta1) instead of nominal anaerobic reaction time (eta), to estimate the amount of available substrate for PAOs, significantly improved model accuracy. Another interesting result of the study was the differences in EBPR characteristics observed in idealized and real conditions.

Topics: Aerobiosis; Anaerobiosis; Bioreactors; Electrons; Fermentation; Glycogen; Hypoxia; Oxygen; Phosphorus; Waste Disposal, Fluid; Water Microbiology; Water Pollutants, Chemical; Water Purification

Anoxia-tolerant animal models are crucial to understand protective mechanisms during low oxygen excursions. As glycogen is the main fermentable fuel supporting energy production during oxygen tension reduction, understanding glycogen metabolism can provide important insights about processes involved in anoxia survival. In this report we studied carbohydrate metabolism regulation in the central nervous system (CNS) of an anoxia-tolerant land snail during experimental anoxia exposure and subsequent reoxygenation. Glucose uptake, glycogen synthesis from glucose, and the key enzymes of glycogen metabolism, glycogen synthase (GS) and glycogen phosphorylase (GP), were analyzed. When exposed to anoxia, the nervous ganglia of the snail achieved a sustained glucose uptake and glycogen synthesis levels, which seems important to maintain neural homeostasis. However, the activities of GS and GP were reduced, indicating a possible metabolic depression in the CNS. During the aerobic recovery period, the enzyme activities returned to basal values. The possible strategies used by Megalobulimus abbreviatus CNS to survive anoxia are discussed.

Topics: Animals; Central Nervous System; Glucose; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Hypoxia; Phosphorylation; Snails

Mechanism of rhodiola root extract adaptogenic activity was studied in rats. The extract was orally administered in rats (100mg/kg body weight), 30 min prior to cold (5 degrees C)-hypoxia (428 mmHg)-restraint (C-H-R) exposure up to fall of T(rec)23 degrees C and recovery (T(rec)37 degrees C) from hypothermia. In untreated control rats serum lactate and non-esterified fatty acids (NEFA) increased on attaining T(rec)23 degrees C with decreased blood enzyme activities hexokinase (HK), phosphofructokinase (PFK), citrate synthase (CS) and glucose-6-phosphate dehydrogenase (G-6-PD), on attaining T(rec)23 degrees C and T(rec)37 degrees C. Decreases were also observed in liver and muscle tissues HK and G-6-PD enzyme activities and liver glycogen and CS on attaining T(rec)23 degrees C and recovery; muscle PFK during recovery; muscle CS on attaining T(rec)23 degrees C. Single and five doses of extract administration restricted increase in serum lactate values of rats on attaining T(rec)23 degrees C and maintained blood NEFA in single dose extract treated animals, indicating improved utilization of NEFA as energy fuel. The single and five doses extract treatment decreased or better maintained tissue glycogen and enzyme activities, viz. HK, PFK, CS and G-6-PD, in blood, liver and muscle, on attaining T(rec)23 degrees C and recovery. The results suggest that rhodiola extract treatment in rats shifted anaerobic metabolism to aerobic, during C-H-R exposure and post stress recovery.

Topics: Animals; Blood Glucose; Cold Temperature; Energy Metabolism; Fatty Acids, Nonesterified; Glycogen; Glycolysis; Hypothermia; Hypoxia; Lactic Acid; Male; Plant Extracts; Plant Roots; Proteins; Rats; Rats, Sprague-Dawley; Restraint, Physical; Rhodiola; Stress, Psychological

The ability to adapt to changing environmental conditions is essential to the fitness of organisms. In some cases, adaptation of the parent alters the offspring's phenotype [1-10]. Such parental effects are adaptive for the offspring if the future environment is similar to the current one but can be maladaptive otherwise [11]. One mechanism by which adaptation occurs is altered provisioning of embryos by the parent [12-16]. Here we show that exposing adult Caenorhabditis elegans to hyperosmotic conditions protects their offspring from these conditions but causes sensitivity to anoxia exposure. We show that this alteration of survival is correlated with changes in the sugar content of adults and embryos. In addition, mutations in gene products that alter sugar homeostasis also alter the ability of embryos to survive in hyperosmotic and anoxic conditions and engage in the adaptive parental effect. Our results indicate that there is a physiological trade-off between the presence of glycerol, which protects animals from hyperosmotic conditions, and glycogen, which is consumed during anoxia. These two metabolites play an essential role in the survival of worms in these adverse environments, and the adaptive parental effect we describe is mediated by the provisioning of these metabolites to the embryo.

Topics: Adaptation, Physiological; Animals; Caenorhabditis elegans; Caenorhabditis elegans Proteins; Embryo, Nonmammalian; Environment; Glycerol; Glycogen; Homeostasis; Hypoxia; Osmotic Pressure; Receptor, Insulin; Stress, Physiological; Survival

In vitro incubation of isolated rodent skeletal muscle is a widely used procedure in metabolic research. One concern with this method is the development of an anoxic state during the incubation period that can cause muscle glycogen depletion. Our aim was to investigate whether in vitro incubation conditions influence glycogen concentration in glycolytic extensor digitorum longus (EDL) and oxidative soleus mouse muscle. Quantitative immunohistochemistry was applied to assess glycogen content in incubated skeletal muscle. Glycogen concentration was depleted, independent of insulin-stimulation in the incubated skeletal muscle. The extent of glycogen depletion was correlated with the oxidative fibre distribution and with the induction of hypoxia-induced-factor-1-alpha. Insulin exposure partially prevented glycogen depletion in soleus, but not in EDL muscle, providing evidence that glucose diffusion is not a limiting step to maintain glycogen content. Our results provide evidence to suggest that the anoxic milieu and the intrinsic characteristics of the skeletal muscle fibre type play a major role in inducing glycogen depletion in during in vitro incubations.

Topics: Animals; Diffusion; Glucose; Glycogen; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Insulin; Mice; Muscle Fibers, Skeletal; Oxidation-Reduction; Tissue Culture Techniques

Several cases of myopathies have been observed in the horse Norman Cob breed. Muscle histology examinations revealed that some families suffer from a polysaccharide storage myopathy (PSSM). It is assumed that a gene expression signature related to PSSM should be observed at the transcriptional level because the glycogen storage disease could also be linked to other dysfunctions in gene regulation. Thus, the functional genomic approach could be conducted in order to provide new knowledge about the metabolic disorders related to PSSM. We propose exploring the PSSM muscle fiber metabolic disorders by measuring gene expression in relationship with the histological phenotype.. Genotypying analysis of GYS1 mutation revealed 2 homozygous (AA) and 5 heterozygous (GA) PSSM horses. In the PSSM muscles, histological data revealed PAS positive amylase resistant abnormal polysaccharides, inflammation, necrosis, and lipomatosis and active regeneration of fibers. Ultrastructural evaluation revealed a decrease of mitochondrial number and structural disorders. Extensive accumulation of an abnormal polysaccharide displaced and partially replaced mitochondria and myofibrils. The severity of the disease was higher in the two homozygous PSSM horses.Gene expression analysis revealed 129 genes significantly modulated (p < 0.05). The following genes were up-regulated over 2 fold: IL18, CTSS, LUM, CD44, FN1, GST01. The most down-regulated genes were the following: mitochondrial tRNA, SLC2A2, PRKCalpha, VEGFalpha. Data mining analysis showed that protein synthesis, apoptosis, cellular movement, growth and proliferation were the main cellular functions significantly associated with the modulated genes (p < 0.05). Several up-regulated genes, especially IL18, revealed a severe muscular inflammation in PSSM muscles. The up-regulation of glycogen synthase kinase-3 (GSK3beta) under its active form could be responsible for glycogen synthase (GYS1) inhibition and hypoxia-inducible factor (HIF1alpha) destabilization.. The main disorders observed in PSSM muscles could be related to mitochondrial dysfunctions, glycogenesis inhibition and the chronic hypoxia of the PSSM muscles.

Topics: Animals; Female; Gene Expression Profiling; Gene Expression Regulation; Genotype; Glycogen; Horse Diseases; Horses; Hypoxia; Inflammation; Male; Mitochondria; Muscle, Skeletal; Muscular Diseases; Phenotype; Polysaccharides

Severe hypoxia exposure and exhaustive exercise in goldfish both elicit a strong activation of substrate-level phosphorylation with the majority of the metabolic perturbations occurring in the white muscle. Approximately half of the muscle glycogen breakdown observed during severe hypoxia exposure was accounted for by ethanol production and loss to the environment, which limited the extent of muscle glycogen recovery when animals were returned to normoxic conditions. Ethanol production in goldfish is not solely a response to anoxia/hypoxia exposure however, as a transient increase in ethanol production was observed during the early stages of recovery from exhaustive exercise. These data suggest that ethanol production is a ubiquitous "anaerobic" end product, which accumulates whenever metabolic demands exceed mitochondrial oxidative potential. Exhaustive exercise and hypoxia exposure both caused a 7 to 8 micromol g(-1) wet mass increase in muscle [lactate] and the rates of recovery following these perturbations were similar. The rates of muscle PCr and pHi recovery after hypoxia exposure and exhaustive exercise were similar with levels returning to controls values within 0.5 h. Surprisingly, liver [glycogen] was not depleted during exposure to severe hypoxia, however, during recovery from both hypoxia and exercise dramatically different responses in liver [glycogen] were noted. During the early stages of recovery, liver [glycogen] transiently increased to high levels after exhaustive exercise, while during recovery from hypoxia there was a transient decrease in liver glycogen over the same time frame. Overall, this points to the liver playing a dramatically different role in facilitating recovery from exercise compared with hypoxia exposure.

Topics: Adenosine Triphosphate; Animals; Energy Metabolism; Ethanol; Glycogen; Goldfish; Hydrogen-Ion Concentration; Hypoxia; Liver; Muscle Fibers, Fast-Twitch; Muscle, Skeletal; Phosphocreatine; Physical Exertion; Recovery of Function; Severity of Illness Index; Time Factors

Nitric oxide (NO) may limit myocardial ischemia-reperfusion injury by slowing the mitochondrial metabolism. We examined whether rat heart contains catalysts potentially capable of reducing nitrite to NO during an episode of regional myocardial ischemia produced by temporary coronary artery occlusion. In intact Sprague-Dawley rats, a 15-min coronary occlusion lowered the nitrite concentration of the myocardial regions exhibiting ischemic glucose metabolism to approximately 50% that of nonischemic regions (185 +/- 223 vs. 420 +/- 203 nmol/l). Nitrite was rapidly repleted during subsequent reperfusion. The heart tissue tested in vitro acquired a substantial ability to consume nitrite when made hypoxic at neutral pH, and this ability was slightly enhanced by simultaneously lowering the pH to 5.5. More than 70% of this activity could be abolished by flushing the coronary circulation with crystalloid to remove trapped erythrocytes. Correspondingly, erythrocytes demonstrated the ability to reduce exogenous nitrite to NO under hypoxic conditions in vitro. In erythrocyte-free heart tissue, the nitrite consumption increased fivefold when the pH was lowered to 5.5. Approximately 40% of this pH-sensitive increase in nitrite consumption could be blocked by the xanthine oxidoreductase inhibitor allopurinol, whereas lowering the Po(2) sufficiently to desaturate myoglobin accelerated it further. We conclude that rat heart contains several factors capable of catalyzing ischemic nitrite reduction; the most potent is contained within erythrocytes and activated by hypoxia, whereas the remainder includes xanthine oxidoreductase and other pH-sensitive factors endogenous to heart tissue, including deoxymyoglobin.

Topics: Allopurinol; Animals; Catalysis; Disease Models, Animal; Enzyme Inhibitors; Erythrocytes; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Male; Myocardial Ischemia; Myocardial Reperfusion Injury; Myocardium; Myoglobin; Nitric Oxide; Nitrites; Oxidation-Reduction; Rats; Rats, Sprague-Dawley; Time Factors; Xanthine Dehydrogenase

Obstructive sleep apnea is characterized by intermittent obstruction of the upper airway, which leads to intermittent hypoxia. Myocardial glycogen is a major energy resource for heart during hypoxia. Previous studies have demonstrated that intermittent hypoxia rapidly degrades myocardial glycogen and activates glycogen synthase (GS). However, the underlying mechanisms remain undefined. Because sleep apnea/intermittent hypoxia usually happens at night, whether intermittent hypoxia leads to GS activation in the postabsorptive state is not known. In the present study, male adult rats were studied after either an overnight fast or ad libitum feeding with or without intermittent ventilatory arrest (3 90-s periods at 10-min intervals). Hearts were quickly excised and freeze-clamped. Intermittent hypoxia induced a significant decrease in myocardial glycogen content in fed rats and stimulated GS in both fasted and fed rats. However, the portion of GS in the active form increased by approximately 38% in fasted rats compared with a larger, approximately 130% increase in fed rats. The basal G-6-P content was comparable in fasted and fed animals and increased approximately threefold after hypoxia. The basal phosphorylation states of Akt and GSK-3beta and the activity of protein phosphatase 1 (PP1) were comparable between fasted and fed control rats. Hypoxia significantly increased Akt phosphorylation and PP1 activity only in fed rats. In contrast, hypoxia did not induce significant change in GSK-3beta phosphorylation in either fasted or fed rats. We conclude that hypoxia activates GS in fed rat myocardium through a combination of rapid glycogenolysis, elevated local G-6-P content, and increased PP1 activity, and fasting attenuates this action independent of local G-6-P content.

Topics: Animals; Blood Glucose; Enzyme Activation; Fasting; Glucose-6-Phosphate; Glycogen; Glycogen Synthase; Glycogen Synthase Kinase 3; Glycogen Synthase Kinase 3 beta; Hypoxia; Insulin; Male; Myocardium; Oncogene Protein v-akt; Phosphoprotein Phosphatases; Protein Phosphatase 1; Rats; Rats, Sprague-Dawley

This study examined the effects of different oxygenation levels and substrate availability on cardiac performance, metabolism, and biochemistry in sexually immature male and female rainbow trout (Oncorhynchus mykiss). Ventricle strips were electrically paced (0.5 Hz, 14 degrees C) in hyperoxic or hypoxic Ringer solution. Our results demonstrate that 1) males sustain isometric force production (F) longer than females under hyperoxia (P O2 = 640 mmHg) with exogenous glucose present; 2) contractility is not maintained under moderate (P O2 = 130 mmHg) or severe hypoxia (P O2 = 10-20 mmHg) with glucose in either sex; however, following reoxygenation, F is higher in females compared with males; and 3) female tissue has higher lactate levels, net lactate efflux, and lactate dehydrogenase activity than males, whereas males have higher glycogen, citrate synthase, and beta-hydroxy acyl-CoA dehydrogenase activities, and greater inotropic responses to exogenous glucose and octanoate. No sex differences were detected in responsiveness to epinephrine and inhibitors of glucose transport or activities of hexokinase and pyruvate kinase. We conclude that sex differences exist in rainbow trout cardiac tissue: females appear to prefer glycolysis for ATP production, whereas males have a higher capacity for aerobic and lipid metabolism.

Topics: Animals; Body Weight; Electric Stimulation; Energy Metabolism; Epinephrine; Fatty Acids; Female; Glucose; Glycogen; Glycolysis; Heart; Heart Rate; Hyperoxia; Hypoxia; In Vitro Techniques; Lactic Acid; Male; Myocardial Contraction; Myocardium; Oncorhynchus mykiss; Organ Size; Oxygen; Sex Characteristics; Vasoconstrictor Agents; Ventricular Function

In response to hypoxia at PO(2) 1.3-1.7 mg/L for 6 h, the kuruma prawn Marsupenaeus (Penaeus) japonicus showed a dramatic decrease in phosphoarginine storage in muscle, with normal levels restored during 4-h post-hypoxic recovery. Large stores of muscle glycogen only decreased between 4 and 6 h during hypoxia, but greatly diminished during recovery. Muscle ATP levels and energy charge decreased only slightly under hypoxia. Lactate levels increased slightly during hypoxia and promptly returned to control levels during recovery. These data indicate that phosphoarginine works in muscle as an ATP buffer during hypoxia and glycogen is utilized as an energy source during recovery. Under hypoxia, up- and down-regulated proteins were identified after 2D electrophoresis and partial sequences were obtained after protease digestion. Fructose bisphosphate aldolase was down-regulated during hypoxia, suggesting the suppression of glycolysis under hypoxia. Several partial sequences from three protein spots up-regulated under hypoxia were all assigned to arginine kinase, suggesting the existence of several isoforms of arginine kinase in the muscle of M. japonicus. This arginine kinase up-regulation under hypoxia may indicate a provision for oxygen re-supply after anaerobiosis. This is consistent with the prompt replenishment of phosphoarginine stores during recovery from hypoxia.

Topics: Adenosine Triphosphate; Amino Acid Sequence; Anaerobiosis; Animals; Arginine; Arginine Kinase; Electrophoresis, Gel, Two-Dimensional; Gene Expression Regulation; Glycogen; Hypoxia; Molecular Sequence Data; Muscles; Organophosphorus Compounds; Penaeidae; Sequence Alignment; Up-Regulation

von Hippel Lindau (VHL) disease is a hereditary cancer syndrome caused by biallelic inactivation of the VHL tumor suppressor gene. The most widely known function of VHL is to limit normoxic protein expression of hypoxia-inducible factor-alpha (HIF-alpha). Loss of the functional VHL gene causes constitutive stabilization of HIF-alpha that primarily up-regulates hypoxia-inducible genes even at normal oxygen concentration, which in turn contribute to VHL tumor progression. We report on the novel function of VHL in hepatic glucose storage and disposal. VHL deletion in adult mouse liver quickly leads to increased accumulation of glycogen granules as well as lipid droplets. This abnormal glycogen storage in VHL-inactivated liver arises at least in part from significantly reduced expression of two key liver-specific glucose metabolism genes, glucose transporter-2 (GLUT2) and glucose-6-phosphatase (G-6-Pase). The expression pattern of these genes in VHL knock-out liver was in contrast to that of well-known HIF target genes, such as PGK, Glut-1, VEGF, and EPO, all of which are highly elevated upon VHL inactivation. Our findings suggest that two distinct signaling pathways exist at the downstream of VHL controlling different sets of gene expression. Following VHL inactivation, one pathway causes oxygen-independent overexpression of classic hypoxia-inducible genes and the other one described here suppresses expression of the genes important for liver glucose metabolism.

Topics: Alleles; Animals; DNA Primers; Gene Deletion; Gene Expression Regulation, Neoplastic; Genotype; Glucose; Glucose Transporter Type 2; Glucose-6-Phosphatase; Glycogen; Hypoxia; Immunohistochemistry; Liver; Mice; Oxygen; Von Hippel-Lindau Tumor Suppressor Protein

We examined the metabolic and ionoregulatory responses of the Amazonian cichlid, Astronotus ocellatus, to 20 h exposure to severe hypoxia (0.37 +/- 0.19 mg O(2)/l; 4.6% air saturation) or 8 h severe hypoxia followed by 12 h recovery in normoxic water. During 20 h exposure to hypoxia, white muscle [ATP] was maintained at normoxic levels primarily through a 20% decrease in [creatine phosphate] (CrP) and an activation of glycolysis yielding lactate accumulation. Muscle lactate accumulation maintained cytoplasmic redox state ([NAD(+)]/[NADH]) and was associated with an inactivation of the mitochondrial enzyme pyruvate dehydrogenase (PDH). The inactivation of PDH was not associated with significant changes in cytoplasmic allosteric modulators ([ADP(free)], redox state, or [pyruvate]). Hypoxia exposure caused an approximately 65% decrease in gill Na(+)/K(+) ATPase activity, which was not matched by changes in Na(+)/K(+) ATPase alpha-subunit protein abundance indicating post-translational modification of Na(+)/K(+) ATPase was responsible for the decrease in activity. Despite decreases in gill Na(+)/K(+) ATPase activity, plasma [Na(+)] increased, but this increase was possibly due to a significant hemoconcentration and fluid shift out of the extracellular space. Hypoxia caused an increase in Na(+)/K(+) ATPase alpha-subunit mRNA abundance pointing to either reduced mRNA degradation during exposure to hypoxia or enhanced expression of Na(+)/K(+) ATPase alpha-subunit relative to other genes.

Topics: Adaptation, Physiological; Adenosine Triphosphate; Animals; Blood Glucose; Cichlids; Creatine; Erythrocyte Indices; Gills; Glycogen; Hematocrit; Hemoglobins; Hydrogen-Ion Concentration; Hypoxia; Ions; Kidney; L-Lactate Dehydrogenase; Lactic Acid; Liver; Muscle Fibers, Fast-Twitch; Oxygen; Phosphocreatine; Pyruvate Dehydrogenase Complex; Pyruvic Acid; RNA, Messenger; Sodium-Potassium-Exchanging ATPase

To investigate the effects of anoxia and glucopenia (A-G) on both male and female guinea pig urinary bladder.. In whole bladders superfused with oxygenated Krebs' solution, intrinsic nerves underwent electrical field stimulation (EFS) and smooth muscle stimulated with carbachol, ATP, and high potassium. The effect of 1, 2, or 3 hr A-G on the contractile response and the ensuing recovery in Krebs' solution, was monitored. Glycogen content in male and female urinary bladders was also measured.. Under different stimuli male urinary bladder proved to contract more efficiently than female organ. After 1 hr A-G the EFS response of male urinary bladder was virtually abolished and returned to 60% of control response in the recovery phase; in female bladder the EFS responses fully recovered during the reperfusion phase. Full recovery of the response to carbachol, ATP, and high potassium stimulations was observed in both genders. A-G had to be extended to 2 hr to cause smooth muscle impairment (higher in male than in female) and a neuronal impairment in female urinary bladders. When 2-deoxyglucose (2-DG), an inhibitor of glycolysis, was added during 1 hr A-G, both neuronal and smooth muscle damages were significantly enhanced in male, as well as, though to a lesser extent, in female bladder. A significantly higher glycogen content was observed in female as compared to male bladders, which was inversely related with the duration of exposure to A-G.. The higher resistance of female urinary bladder to A-G/reperfusion, can be partly ascribed to the higher glycogen content.

Topics: Adenosine Triphosphate; Animals; Carbachol; Cholinergic Agonists; Deoxyglucose; Female; Glucose; Glycogen; Guinea Pigs; Hypoxia; In Vitro Techniques; Male; Muscle Contraction; Muscle, Smooth; Peripheral Nervous System; Potassium Chloride; Reperfusion Injury; Sex Characteristics; Urinary Bladder

To test the hypothesis that submergence temperature affects the distribution of the lactate load and glycogen utilization during anoxia in turtles, we sampled a variety of tissues after 7 days, 24 h, and 4 h of anoxic submergence at 5, 15, and 25 degrees C, respectively. These anoxic durations were chosen because we found that they produced similar decreases in plasma HCO(3)(-) ( approximately 18-22 meq/l). The sampled tissues included ventricle, liver, small intestine, carapace, and the following muscles: flexor digitorum longus, retrahens capitis, iliofibularis, and pectoralis. Shell and skeleton sequestered 41.9, 34.1, and 26.1% of the estimated lactate load at 5, 15, and 25 degrees C. The changes in plasma Ca(2+) and Mg(2+), relative to the estimated lactate load, decreased with increased temperature, indicating greater buffer release from bone at colder temperatures. Tissue lactate contents, relative to plasma lactate, increased with the temperature of the submergence. Glucose mobilization and tissue glycogen utilization were more pronounced at 15 and 25 degrees C than at 5 degrees C. We conclude that, in slider turtles, the ability of the mineralized tissue to participate in the buffering of lactic acid during anoxia is inversely related to temperature, causing the lactate burden to shift to the tissues at warmer temperatures. Muscles utilize glycogen during anoxia more at warmer temperatures.

Topics: Acclimatization; Acid-Base Equilibrium; Animals; Bicarbonates; Blood Glucose; Bone and Bones; Calcium; Carbon Dioxide; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Lactic Acid; Magnesium; Muscle, Skeletal; Oxygen; Temperature; Turtles

After birth, constriction of the full-term ductus arteriosus induces oxygen, glucose and ATP depletion, cell death, and anatomic remodeling of the ductus wall. The immature ductus frequently fails to develop the same degree of constriction or anatomic remodeling after birth. In addition, the immature ductus loses its ability to respond to vasoconstrictive agents, like oxygen or indomethacin, with increasing postnatal age. We examined the effects of premature delivery and postnatal constriction on the immature baboon ductus arteriosus. By 6 days after birth, surrogate markers of hypoxia (HIF1alpha/VEGF mRNA) and cell death [dUTP nick-end labeling (TUNEL)-staining] increased, while glucose and ATP concentrations (bioluminescence imaging) decreased in the immature ductus. TUNEL-staining was significantly related to the degree of glucose and ATP depletion. Glucose and ATP depletion were directly related to the degree of ductus constriction; while TUNEL-staining was logarithmically related to the degree of ductus constriction. Extensive cell death (>15% TUNEL-positive cells) occurred only when there was no Doppler flow through the ductus lumen. In contrast, HIF1alpha/VEGF expression and ATP concentrations were significantly altered even when the immature ductus remained open after birth. Decreased ATP concentrations produced decreased oxygen-induced contractile responses in the immature ductus. We hypothesize that ATP depletion in the persistently patent immature newborn ductus is insufficient to induce cell death and remodeling but sufficient to decrease its ability to constrict after birth. This may explain its decreasing contractile response to oxygen, indomethacin, and other contractile agents with increasing postnatal age.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Cell Death; Ductus Arteriosus; Gene Expression Regulation; Glucose; Glycogen; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Papio; Sheep; Vascular Endothelial Growth Factor A

Topics: Animals; Anura; Fructose-Bisphosphatase; Glycogen; Glycolysis; Humans; Hypoxia; Lactates; Liver; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle, Skeletal; Pyruvate Kinase

Changes in the number of Na+-K+-ATPase alpha-subunits, Na+-K+-ATPase activity and glycogen content of the crucian carp (Carassius carassius) brain were examined to elucidate relative roles of energy demand and supply in adaptation to seasonal anoxia. Fish were collected monthly around the year from the wild for immediate laboratory assays. Equilibrium dissociation constant and Hill coefficient of [3H]ouabain binding to brain homogenates were 12.87+/-2.86 nM and -1.18+/-0.07 in June and 11.93+/-2.81 nM and -1.17+/-0.06 in February (P>0.05), respectively, suggesting little changes in Na+-K+-ATPase alpha-subunit composition of the brain between summer and winter. The number of [3H]ouabain binding sites and Na-K-ATPase activity varied seasonally (P<0.001) but did not show clear connection to seasonal changes in oxygen content of the fish habitat. Six weeks' exposure of fish to anoxia in the laboratory did not affect Na+-K+-ATPase activity (P>0.05) confirming the anoxia resistance of the carp brain Na pump. Although anoxia did not suppress the Na pump, direct Q10 effect on Na+-K+-ATPase at low temperatures resulted in 10 times lower catalytic activity in winter than in summer. Brain glycogen content showed clear seasonal cycling with the peak value of 203.7+/-16.1 microM/g in February and a 15 times lower minimum (12.9+/-1.2) in July. In winter glycogen stores are 15 times larger and ATP requirements of Na+-K+-ATPase at least 10 times less than in summer. Accordingly, brain glycogen stores are sufficient to fuel brain function for about 8 min in summer and 16 h in winter, meaning about 150-fold extension of brain anoxia tolerance by seasonal changes in energy supply-demand ratio.

Topics: Animals; Brain; Carps; Glycogen; Hypoxia; Ouabain; Seasons; Sodium-Potassium-Exchanging ATPase; Temperature; Tritium

To investigate the effect of anoxia/glucopenia and re-superfusion on intrinsic nerves in the mammalian urinary bladder.. Strips of detrusor smooth muscle were dissected from monkey and human urinary bladder and mounted for tension recording in organ baths superfused with Krebs solution. Human, monkey, and guinea-pig urinary bladders were treated to evaluate glycogen contents by a biochemical method.. Detrusor strips from both monkeys and humans had to be exposed to anoxia-glucopenia for up to 2-2.5 hr to observe a progressive decline in the response to electrical field stimulation (EFS) of the intrinsic nerves, at variance with guinea-pig detrusor strips. In contrast, the response to direct activation of the smooth muscle with carbachol remained almost unaltered. Incubation of human and monkey detrusor strips with 2-deoxyglucose (2-DG) during 1 hr anoxia-glucopenia, however, caused a marked damage to the intrinsic nerves. The glycogen contents of both human detrusor specimens and monkey urinary bladders were 2.0- and 1.4-fold higher, respectively, than that found in guinea-pig urinary bladder; furthermore, untreated monkey detrusor sections showed a greater number of glycogen granules as compared to those subjected to anoxia-glucopenia and re-superfusion. In guinea-pig and in monkey detrusor sections glycogen granules were found in smooth muscle cells but not in neurons of intramural ganglia.. A higher susceptibility of guinea-pig as compared to monkey and human nerves has been demonstrated; it is suggested that anaerobic glucose metabolism during anoxia-glucopenia is crucial for the functional recovery of detrusor intrinsic nerves from damage caused by anoxia-glucopenia and re-superfusion.

Topics: Anaerobiosis; Animals; Antimetabolites; Carbachol; Cebus; Deoxyglucose; Electric Stimulation; Ganglia, Autonomic; Glucose; Glycogen; Glycolysis; Guinea Pigs; Humans; Hypoxia; In Vitro Techniques; Ischemia; Muscarinic Agonists; Muscle, Smooth; Oxidative Stress; Regional Blood Flow; Reperfusion Injury; Urinary Bladder

The effects of graded hypoxia on the physiological and biochemical responses were examined in two closely related species of cichlids of the Amazon: Astronotus crassipinnis and Symphysodon aequifasciatus. Ten fish of each species were exposed to graded hypoxia for 8 h in seven oxygen concentrations (5.92, 3.15, 1.54, 0.79, 0.60, 0.34, and 0.06 mg O(2) L(-)(1)), with the aim to evaluate hypoxia tolerance and metabolic adjustments, where plasma glucose and lactate levels, hepatic and muscle glycogen contents, and maximum enzyme activities (PK, LDH, MDH and CS) in skeletal and cardiac muscles were measured. Another experimental set was done to quantify oxygen consumption (MO(2)) and opercular movements in two oxygen concentrations. Hypoxia tolerance differed between the two species. Astronotus crassipinnis was able to tolerate anoxia for 178 min while S. aequifasciatus was able to withstand 222 min exposure in deep hypoxia (0.75 mg O(2) L(-)(1)). Suppressed MO(2) was observed during exposure to 0.34 (A. crassipinnis) and 0.79 mg O(2) L(-)(1) (S. aequifasciatus), while opercular movements increased in both species exposed to hypoxia. Higher levels of muscle and liver glycogen and larger hypoxia-induced increases in plasma glucose and lactate were observed in A. crassipinnis, which showed a higher degree of hypoxia tolerance. Changes in enzyme levels were tissue-specific and differed between species suggesting differential abilities in down-regulating oxidative pathways and increasing anaerobic metabolism. Based on the present data, we conclude that these animals are good anaerobes and highly adapted to their environment, which is allowed by their abilities to regulate metabolic pathways and adjust their enzyme levels.

Topics: Adaptation, Physiological; Anaerobic Threshold; Animals; Cichlids; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lactic Acid; Malate Dehydrogenase; Muscle, Skeletal; Myocardium; Oxygen; Oxygen Consumption

Altitude training is a frequently used method for enhancing endurance performance in athletes. But its acute effect on carbohydrate metabolism in cardiac muscle is unknown. In this study, we determined the acute effect of an exercise-hypoxia challenge on glycogen storage and GLUT4 protein expression in heart muscle. Sixteen male Sprague-Dawley rats were assigned to one of two groups: control (CTRL) and exercise-hypoxia (EX+HY). The exercise protocol consisted of swimming for 180 min twice, with a 45-min rest interval. Five hours after the exercise, the EX+HY rats were exposed to a 14% O(2) systemic hypoxia under normobaric condition for 12 h. After this hypoxia exposure, the EX+HY and control rats were given glucose orally (1 g/kg body weight) with stomach tube and recovered under normal condition for 16 h. Ventricular portion of the heart was used to determine the levels of glycogen, GLUT4 mRNA, and GLUT4 protein after recovery. We found that myocardial glycogen level was lowered by the exercise-hypoxia challenge (51% below control, p < 0.05), while GLUT4 mRNA was dramatically elevated (approximately 400% of the control level, p < 0.05). The acute exercise-hypoxia treatment did not affect GLUT1 protein level in the same tissue. The novel finding of the study was that the exercise-hypoxia treatment significantly induced GLUT4 gene expression in the cardiac muscle. This acute response appears to be associated with a sustained glycogen depletion of the muscle.

Topics: Altitude; Animals; Blood Glucose; Blotting, Western; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Hypoxia; Male; Myocardium; Physical Conditioning, Animal; Physical Exertion; Rats; Rats, Sprague-Dawley; RNA, Messenger; Time Factors

In many vertebrates, a short episode of oxygen lack protects against myocardial necrosis during a subsequent, longer period of oxygen deprivation. This protective effect, termed preconditioning, also improves the functional recovery. Improved functional recovery has been reported for hypoxia-sensitive, in situ perfused rainbow trout hearts, but appears absent in another strain of rainbow trout that has a more hypoxia-tolerant heart. The results for the hypoxia-tolerant rainbow trout heart, however, might have occurred because the preconditioning stimuli were insufficient in either intensity or type to elicit cardioprotective effects. In the present study, we attempted to induce preconditioning in in situ perfused hearts from hypoxia-tolerant rainbow trout ( Oncorhynchus mykiss), acclimated and tested at 10 degrees C, by either doubling the anoxic preconditioning stimulus (PO(2) of the perfusate <0.5 kPa) relative to earlier studies or by using short exposures to high concentrations of adrenaline. In addition, anoxic-preconditioning experiments were conducted at an acutely elevated temperature (15 degrees C) to increase myocardial sensitivity to oxygen lack. The effect of preconditioning stimuli was assessed by measuring cardiac performance before and after exposure to a 20-min anoxic challenge. In addition, myocardial condition was evaluated at the termination of the experiment by measuring myocardial concentrations of glycogen, high energy phosphates and lactate, as well as activities of pyruvate kinase and lactate dehydrogenase. Maximal cardiac performance in oxygenated control hearts was unchanged by the 2-h experimental protocol, whereas inclusion of a 20-min period of anoxia led to 25 and 35% reductions in maximal cardiac performance at 10 and 15 degrees C, respectively. Reduced contractility, however, could not be ascribed to myocardial necrosis, as the biochemical and energy state of the hearts was unaffected. Hence, anoxic exposure merely stunned the myocardium. At 10 degrees C, neither the anoxic nor adrenergic preconditioning protocols improved post-anoxic cardiac performance. Further, the preconditioning protocols did not reduce post-anoxic myocardial dysfunction at 15 degrees C, despite the increased cardiac sensitivity to anoxia at this temperature. Thus, despite using strong and different preconditioning stimuli compared with earlier studies, the cardio-protective effect of preconditioning seems to be absent in rainbow trout hearts that are

Topics: Analysis of Variance; Animals; Cardiac Output; Epinephrine; Glycogen; Heart; Heart Rate; Hypoxia; Ischemic Preconditioning, Myocardial; Lactic Acid; Muscle, Skeletal; Myocardium; Oncorhynchus mykiss; Spectrophotometry; Temperature

This study investigated the regulation of glucose uptake in Atlantic cod (Gadus morhua) hearts. Isolated hearts were perfused with or without glucose in the medium, under either normoxic or severely hypoxic conditions. Working at basal levels, hearts did not require extracellular glucose to maintain power under aerobic conditions. However, cardiac performance was significantly reduced without exogenous glucose under oxygen-limiting conditions. The addition of the glucose transporter inhibitor cytochalasin B caused hypoxic hearts to fail early, and hearts perfused with a glucose analogue, 2-deoxyglucose (2-DG), increased glucose uptake 3-fold under hypoxia. The uptake of 2-DG was only partially inhibited when cytochalasin B was added to the medium. Isolated ventricle strips were also incubated in the presence of 2-DG and the extracellular marker mannitol. Glucose uptake (glucose transport plus intracellular phosphorylation) was assessed by measuring the initial rate of 2-deoxyglucose-6-phosphate (2-DG-6-P) accumulation. At 1 mmol l(-1) 2-DG, the rate of 2-DG uptake remained linear for 60 min, and 2-DG-6-P, but not free 2-DG, accumulation was increased. The fact that intracellular 2-DG did not increase indicates that glucose transport is the rate-limiting step for glucose utilization in non-stimulated cardiac tissue. Replacement of Na(+) by choline in the incubation medium did not affect 2-DG uptake, providing evidence that Na(+)-coupled glucose transport is absent in cod cardiac tissue. Similar to cytochalasin B, glucose uptake was also inhibited by phloridzin, suggesting that facilitated, carrier-mediated glucose transport occurs in cod hearts. Under the conditions employed in these experiments, it is clear that (1) activation of glucose transport is required to support hypoxic performance, (2) the rate-limiting step for glucose utilization is glucose transport rather than glucose phosphorylation, (3) 2-DG uptake accurately reflects glucose transport activity and (4) glucose uptake in cod hearts does not involve an Na(+)-dependent mechanism.

Topics: Analysis of Variance; Animals; Biological Transport, Active; Cytochalasin B; Deoxyglucose; Fishes; Glucose; Glucose-6-Phosphate; Glycogen; Heart; Hypoxia; Lactic Acid; Mannitol; Myocardium; Phlorhizin; Sodium; Time Factors

Topics: Animals; Glycogen; Humans; Hypoxia; Myocardium; Rats; Turtles

The physiological flux of oxygen is extreme in exercising skeletal muscle. Hypoxia is thus a critical parameter in muscle function, influencing production of ATP, utilization of energy-producing substrates, and manufacture of exhaustion-inducing metabolites. Glycolysis is the central source of anaerobic energy in animals, and this metabolic pathway is regulated under low-oxygen conditions by the transcription factor hypoxia-inducible factor 1alpha (HIF-1alpha). To determine the role of HIF-1alpha in regulating skeletal muscle function, we tissue-specifically deleted the gene encoding the factor in skeletal muscle. Significant exercise-induced changes in expression of genes are decreased or absent in the skeletal-muscle HIF-1alpha knockout mice (HIF-1alpha KOs); changes in activities of glycolytic enzymes are seen as well. There is an increase in activity of rate-limiting enzymes of the mitochondria in the muscles of HIF-1alpha KOs, indicating that the citric acid cycle and increased fatty acid oxidation may be compensating for decreased flow through the glycolytic pathway. This is corroborated by a finding of no significant decreases in muscle ATP, but significantly decreased amounts of lactate in the serum of exercising HIF-1alpha KOs. This metabolic shift away from glycolysis and toward oxidation has the consequence of increasing exercise times in the HIF-1alpha KOs. However, repeated exercise trials give rise to extensive muscle damage in HIF-1alpha KOs, ultimately resulting in greatly reduced exercise times relative to wild-type animals. The muscle damage seen is similar to that detected in humans in diseases caused by deficiencies in skeletal muscle glycogenolysis and glycolysis. Thus, these results demonstrate an important role for the HIF-1 pathway in the metabolic control of muscle function.

Topics: Adenosine Triphosphate; Alleles; Animals; Creatine Kinase; Crosses, Genetic; Gene Deletion; Gene Expression Regulation; Genotype; Glucose; Glycogen; Glycolysis; Hematocrit; Hemoglobins; Hypoxia; Hypoxia-Inducible Factor 1, alpha Subunit; Lactic Acid; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Microscopy, Electron; Muscle, Skeletal; Oxygen; Physical Conditioning, Animal; Physical Exertion; Polymerase Chain Reaction; Promoter Regions, Genetic; Reverse Transcriptase Polymerase Chain Reaction

Altitude training is a common method used to enhance endurance performance in athletes. We have examined the interactive effect of exercise training and chronic hypoxic on glycogen storage and GLUT4 protein expression in cardiac muscles. Thirty-two male Sprague-Dawley rats were weight balanced and assigned to one of the following four groups: control, exercise, hypoxia, and hypoxia-exercise. Rats with hypoxic treatment (breathing 14% O(2) for 12 hr/d) were exposed under normobaric conditions. The training protocol consisted of swimming for two 3-hr periods per day for 4 weeks. Glycogen content, GLUT4 protein, and mRNA of all rats were determined 16 hr after treatments. Four-week exercise training without hypoxia significantly elevated myocardial glycogen level by 45%. The chronic hypoxic-exercise training elevated the myocardial glycogen level by 67% above control level, significantly greater than the exercise group. Chronic hypoxia, exercise training, and hypoxia-exercise training significantly elevated GLUT4 protein by 40-70% in cardiac muscles. Chronic hypoxia significantly elevates the GLUT1 protein level independent of exercise training. The new finding in this study was that GLUT4 gene expression in cardiac muscle can be stimulated by exercise training with hypoxia treatments. This molecular adaptation appears to be associated with the observed increase in glycogen storage of the muscle.

Topics: Altitude; Animals; Glucose Transporter Type 4; Glycogen; Heart; Hypoxia; Male; Monosaccharide Transport Proteins; Muscle Proteins; Physical Conditioning, Animal; Rats; Rats, Sprague-Dawley

Recently, rapid and transient cardiac pacing was shown to induce preconditioning in animal models. Whether the electrical stimulation per se or the concomitant myocardial ischemia affords such a protection remains unknown. We tested the hypothesis that chronic pacing of a cardiac preparation maintained in a normoxic condition can induce protection. Hearts of 4-day-old chick embryos were electrically paced in ovo over a 12-h period using asynchronous and intermittent ventricular stimulation (5 min on-10 min off) at 110% of the intrinsic rate. Sham (n = 6) and paced hearts (n = 6) were then excised, mounted in vitro, and subjected successively to 30 min of normoxia (20% O(2)), 30 min of anoxia (0% O(2)), and 60 min of reoxygenation (20% O(2)). Electrocardiogram and atrial and ventricular contractions were simultaneously recorded throughout the experiment. Reoxygenation-induced chrono-, dromo-, and inotropic disturbances, incidence of arrhythmias, and changes in electromechanical delay (EMD) in atria and ventricle were systematically investigated in sham and paced hearts. Under normoxia, the isolated heart beat spontaneously and regularly, and all baseline functional parameters were similar in sham and paced groups (means +/- SD): heart rate (190 +/- 36 beats/min), P-R interval (104 +/- 25 ms), mechanical atrioventricular propagation (20 +/- 4 mm/s), ventricular shortening velocity (1.7 +/- 1 mm/s), atrial EMD (17 +/- 4 ms), and ventricular EMD (16 +/- 2 ms). Under anoxia, cardiac function progressively collapsed, and sinoatrial activity finally stopped after approximately 9 min in both groups. During reoxygenation, paced hearts showed 1) a lower incidence of arrhythmias than sham hearts, 2) an increased rate of recovery of ventricular contractility compared with sham hearts, and 3) a faster return of ventricular EMD to basal value than sham hearts. However, recovery of heart rate, atrioventricular conduction, and atrial EMD was not improved by pacing. Activity of all hearts was fully restored at the end of reoxygenation. These findings suggest that chronic electrical stimulation of the ventricle at a near-physiological rate selectively alters some cellular functions within the heart and constitutes a nonischemic means to increase myocardial tolerance to a subsequent hypoxia-reoxygenation.

Topics: Animals; Atrioventricular Node; Cardiac Pacing, Artificial; Chick Embryo; Electrocardiography; Electrophysiology; Glycogen; Heart; Heart Atria; Heart Rate; Hypoxia; Ischemic Preconditioning, Myocardial; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Oxygen Consumption; Proteins; Ventricular Function

The dauer larva, a non-feeding and developmentally arrested stage of the free-living nematode Caenorhabditis elegans, is morphologically and physiologically specialized for survival and dispersal during adverse growth conditions. The ability of dauer larvae to live several times longer than the continuous developmental life span has been attributed in part to a repressed metabolism. We used serial analysis of gene expression (SAGE) profiles from dauer larvae and mixed growing stages to compare expression patterns for genes with known or predicted roles in glycolysis, gluconeogenesis, glycogen metabolism, the Krebs and glyoxylate cycles, and selected fermentation pathways. Ratios of mixed:dauer transcripts indicated non-dauer enrichment that was consistent with previously determined adult:dauer enzyme activity ratios for hexokinase (glycolysis), phosphoenolpyruvate carboxykinase and fructose 1,6-bisphosphatase (gluconeogenesis), isocitrate dehydrogenase (NADP-dependent), and isocitrate lyase-malate synthase (glyoxylate cycle). Transcripts for the majority of Krebs cycle components were not differentially represented in the two profiles. Transcript abundance for pyruvate kinase, alcohol dehydrogenase, a putative cytosolic fumarate reductase, two pyruvate dehydrogenase components, and a succinyl CoA synthetase alpha subunit implied that anaerobic pathways were upregulated in dauer larvae. Generation of nutritive fermentation byproducts and the moderation of oxidative damage are potential benefits of a hypoxic dauer interior.

Topics: Alcohols; Anaerobiosis; Animals; Base Sequence; Caenorhabditis elegans; Carbohydrate Metabolism; Citric Acid Cycle; Energy Metabolism; Fermentation; Gene Expression Profiling; Gluconeogenesis; Glycogen; Glycolysis; Glyoxylates; Hypoxia; Larva; Mitochondria; Molecular Sequence Data; Nucleic Acid Conformation; Pyruvate Dehydrogenase Complex; Succinate Dehydrogenase; Succinic Acid

In large- and medium-sized arteries, the diffusion distances for oxygen and nutrients are long. This has been suggested to make these vessels prone to develop local energy metabolic deficiencies that could contribute to atherogenesis. To validate this hypothesis, we introduced a new method to measure energy metabolites within the arterial wall at high spatial resolution.. Bioluminescence imaging was used to quantify local metabolite concentrations in cryosections of snap frozen (in vivo) and incubated pig carotid artery rings. Incubation at hypoxia resulted in increased lactate concentrations, whereas ATP, glucose, and glycogen concentrations were decreased, especially in the mid media, where concentrations of these metabolites were close to zero. In snap frozen arteries, glycogen concentrations were markedly higher in deep layers of the media than toward the lumen. ATP, glucose, and lactate were more homogenously distributed.. Bioluminescence imaging is a new and powerful tool to assess arterial wall energy metabolism at high spatial resolution. Our experiments demonstrate heterogeneous distributions of energy metabolites under hypoxic in vitro conditions. Furthermore, we show that glycogen concentrations are higher in deep medial layers in vivo. This might represent a local adaptation to a low-oxygen microenvironment.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Carotid Arteries; Cryopreservation; Energy Metabolism; Frozen Sections; Glucose; Glycogen; Hypoxia; Image Processing, Computer-Assisted; In Vitro Techniques; Lactic Acid; Luciferases; Luminescent Measurements; Oxygen; Swine; Up-Regulation

A model to study glycogen supercompensation (the significant increase in glycogen content above basal level) in primary rat skeletal muscle culture was established. Glycogen was completely depleted in differentiated myotubes by 2 h of electrical stimulation or exposure to hypoxia during incubation in medium devoid of glucose. Thereafter, cells were incubated in medium containing glucose, and glycogen supercompensation was clearly observed in treated myotubes after 72 h. Peak glycogen levels were obtained after 120 h, averaging 2.5 and 4 fold above control values in the stimulated- and hypoxia-treated cells, respectively. Glycogen synthase activity increased and phosphorylase activity decreased continuously during 120 h of recovery in the treated cells. Rates of 2-deoxyglucose uptake were significantly elevated in the treated cells at 96 and 120 h, averaging 1.4-2 fold above control values. Glycogenin content increased slightly in the treated cells after 48 h (1.2 fold vs. control) and then increased considerably, achieving peak values after 120 h (2 fold vs. control). The results demonstrate two phases of glycogen supercompensation: the first phase depends primarily on activation of glycogen synthase and inactivation of phosphorylase; the second phase includes increases in glucose uptake and glycogenin level.

Topics: Adenosine Triphosphate; Animals; Cell Differentiation; Deoxyglucose; Electric Stimulation; Glucose; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Hypoxia; Muscle, Skeletal; Rats; Time Factors

Elevated glycogen levels in heart have been shown to have cardioprotective effects against ischemic injury. We have therefore established a model for elevating glycogen content in primary rat cardiac cells grown in culture and examined potential mechanisms for the elevation (glycogen supercompensation). Glycogen was depleted by exposing the cells to hypoxia for 2 h in the absence of glucose in the medium. This was followed by incubating the cells with 28 mM glucose in normoxia for up to 120 h. Hypoxia decreased glycogen content to about 15% of control, oxygenated cells. This was followed by a continuous increase in glycogen in the hypoxia treated cells during the 120 h recovery period in normoxia. By 48 h after termination of hypoxia, the glycogen content had returned to baseline levels and by 120 h glycogen was about 150% of control. The increase in glycogen at 120 h was associated with comparable relative increases in glucose uptake (approximately 180% of control) and the protein level of the glut-1 transporter (approximately 170% of control), whereas the protein level of the glut-4 transporter was decreased to < 10% of control. By 120 h, the hypoxia-treated cells also exhibited marked increases in the total (approximately 170% of control) and fractional activity of glycogen synthase (control, approximately 15%; hypoxia-treated, approximately 30%). Concomitantly, the hypoxia-treated cells also exhibited marked decreases in the total (approximately 50% of control) and fractional activity of glycogen phosphorylase (control, approximately 50%; hypoxia-treated, approximately 25%). Thus, we have established a model of glycogen supercompensation in cultures of cardiac cells that is explained by concerted increases in glucose uptake and glycogen synthase activity and decreases in phosphorylase activity. This model should prove useful in studying the cardioprotective effects of glycogen.

Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Creatine Kinase; Glucose; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Glycogen Phosphorylase; Glycogen Synthase; Hypoxia; Monosaccharide Transport Proteins; Muscle Proteins; Myocardium; Rats; Time Factors

Evidence has accumulated that activation of AMP kinase (AMPK) mediates the acute increase in glucose transport induced by exercise. As the exercise-induced, insulin-independent increase in glucose transport wears off, it is followed by an increase in muscle insulin sensitivity. The major purpose of this study was to determine whether hypoxia and 5-aminoimidazole-4-carboxamide-1-beta-D-ribofuranoside (AICAR), which also activate AMPK and stimulate glucose transport, also induce an increase in insulin sensitivity. We found that the increase in glucose transport in response to 30 microU/ml insulin was about twofold greater in rat epitrochlearis muscles that had been made hypoxic or treated with AICAR 3.5 h previously than in untreated control muscles. This increase in insulin sensitivity was similar to that induced by a 2-h bout of swimming or 10 min of in vitro electrically stimulated contractions. Neither phosphatidylinositol 3-kinase activity nor protein kinase B (PKB) phosphorylation in response to 30 microU/ml insulin was enhanced by prior exercise or AICAR treatment that increased insulin sensitivity of glucose transport. Inhibition of protein synthesis by inclusion of cycloheximide in the incubation medium for 3.5 h after exercise did not prevent the increase in insulin sensitivity. Contractions, hypoxia, and treatment with AICAR all caused a two- to three-fold increase in AMPK activity over the resting level. These results provide evidence that the increase in insulin sensitivity of muscle glucose transport that follows exercise is mediated by activation of AMPK and involves a step beyond PKB in the pathway by which insulin stimulates glucose transport.

Topics: Acetylcarnitine; Adenylate Kinase; Animals; Biological Transport; Cycloheximide; Enzyme Activation; Glucose; Glycogen; Hypoxia; Insulin; Insulin Resistance; Male; Muscle Contraction; Muscle, Skeletal; Protein Synthesis Inhibitors; Rats; Rats, Wistar; Signal Transduction

We evaluated the effects of freezing, dehydration and anoxia stresses on muscle PP-1 activity in the freeze-tolerant amphibian, Rana sylvatica. In addition, PP-1 catalytic subunit (PP-1c) was purified to homogeneity to assess the biochemical properties of the enzyme from a freeze-tolerant vertebrate. Freezing stimulated a rise in the amount of active PP-1 (70% above the control) at 20 min post-nucleation. With longer freezing (1-12 h), the amount of active enzyme returned to control levels, and the amount of total PP-1 fell, decreasing by up to 43%. This decline in total PP-1 kept the % active at a high value throughout the freeze. Anoxia exposure (12 h) reduced the active PP-1 by 60%, but had no effect on total PP-1 activity. Neither dehydration nor rehydration had any significant effect on the amounts of either total or active PP-1. PP-1 activity associated with the myofibril fraction increased, while activity associated with the glycogen pellet decreased in response to freezing and dehydration, but not anoxia. Purified frog PP-1c showed a variety of properties that are typical of the enzyme from other sources. In addition, the enzyme was strongly inhibited by AMP and weakly by ADP and ATP; the physiological relevance of inhibition by nucleotides remains to be determined. Overall, the results suggest an important role for PP-1 in signal transduction in the skeletal muscle of freeze-tolerant amphibians.

Topics: Adaptation, Physiological; Animals; Cold Temperature; Cytosol; Dehydration; Enzyme Stability; Freezing; Glycogen; Hypoxia; Kinetics; Muscle, Skeletal; Myofibrils; Phosphoprotein Phosphatases; Ranidae; Time Factors

Harvesting trauma to the graft dramatically decreases survival after liver transplantation. Since activated Kupffer cells play a role in primary nonfunction, the purpose of this study was to test the hypothesis that organ manipulation activates Kupffer cells. To mimic what occurs with donor hepatectomy, livers from Sprague-Dawley rats underwent dissection with or without gentle organ manipulation in a standardized manner in situ. Perfused livers exhibited normal values for O(2) uptake (105 +/- 5 micromol. g(-1). h(-1)) measured polarigraphically; however, 2 h after organ manipulation, values increased significantly to 160 +/- 8 micromol. g(-1). h(-1) and binding of pimonidazole, a hypoxia marker, increased about threefold (P < 0.05). Moreover, Kupffer cells from manipulated livers produced three- to fourfold more tumor necrosis factor-alpha and PGE(2), whereas intracellular calcium concentration increased twofold after lipopolysaccharide compared with unmanipulated controls (P < 0.05). Gadolinium chloride and glycine prevented both activation of Kupffer cells and effects of organ manipulation. Furthermore, indomethacin given 1 h before manipulation prevented the hypermetabolic state, hypoxia, depletion of glycogen, and release of PGE(2) from Kupffer cells. These data indicate that gentle organ manipulation during surgery activates Kupffer cells, leading to metabolic changes dependent on PGE(2) from Kupffer cells, which most likely impairs liver function. Thus modulation of Kupffer cell function before organ harvest could be beneficial in human liver transplantation and surgery.

Topics: Animals; Cells, Cultured; Dinoprostone; Female; Glycogen; Hypoxia; Kupffer Cells; Liver; Liver Diseases; Physical Stimulation; Rats; Rats, Sprague-Dawley; Tumor Necrosis Factor-alpha

Short-term (24 h) effects of four stressors (hypoxia, hyperoxia, potassium dichromate, fenitrothion) on the activity of the electron transport system (ETS) and total lipid, glycogen and protein contents were assessed in 4th instar larvae of Chironomus riparius. Hypoxia and hyperoxia caused an increase in ETS activity and protein content. Glycogen content decreased when larvae were placed under hypoxic conditions. ETS activity increased following exposure to 2 microg x l(-1) of fenitrothion. It decreased in larvae exposed to 20 microg x l(-1) of this insecticide. A decrease in lipid and glycogen contents was observed in larvae exposed to potassium dichromate or fenitrothion. Changes in ETS activity and lipid and glycogen contents may be related to the activation of the respiratory chain due to an increase in energy cost associated with homeostatic phenomena, such as detoxification processes. These results suggest that some parameters related to energy metabolism, such as ETS activity and lipid and glycogen contents, may be used as biomarkers of environmental disturbance in Chironomus riparius larvae.

Topics: Animals; Chironomidae; Energy Metabolism; Fenitrothion; Glycogen; Hyperoxia; Hypoxia; Larva; Lipid Metabolism; Oxygen; Potassium Dichromate

The aim was to identify the major ATP source controlling the activity of sarcolemmal K(ATP) channels in ventricular cardiomyocytes.. K(ATP)-channel current (I(KATP)) was measured with the patch-clamp technique in either the whole-cell (glycogenolysis blocked by 10 mmol/l EGTA), cell-attached, or inside-out configuration.. In the absence of any substrate, I(KATP) (amplitude 31+/-4 nA; n=5) appeared spontaneously 520+/-160 s (n=6) after whole-cell access. This latency was shortened by exposure to anoxia (117+/-33 s, n=32) and even more by uncoupling (1-10 micromol/l FCCP; 25+/-3 s; n=13) while the amplitude was unchanged. During metabolic inhibition the latency was remarkably prolonged when the F1F0-ATPase was blocked by oligomycin, suggesting that under those conditions the F1F0-ATPase is the major ATP consumer. Glucose (5.5-20.0 mmol/l) in the bath solution did not affect the amplitude of I(KATP) but prolonged its latency compared to respective substrate-free conditions. However, I(KATP) was blocked immediately by mitochondrial substrates. FCCP also induced large I(KATP) in cell-attached measurements in either the absence or presence of glucose and oligomycin.. The activity of K(ATP) channels in cardiomyocytes of mice is controlled by a cytosolic [ATP] pool for which oxidative phosphorylation is the predominant ATP source.

Topics: Adenosine Triphosphate; Animals; Carbonyl Cyanide p-Trifluoromethoxyphenylhydrazone; Cytosol; Egtazic Acid; Enzyme Inhibitors; Glucose; Glycogen; Heart Ventricles; Hypoxia; Mice; Mitochondria, Heart; Myocardium; Oligomycins; Oxidative Phosphorylation; Patch-Clamp Techniques; Potassium Channels; Proton-Translocating ATPases; Pyruvic Acid; Uncoupling Agents

Although the two curculionid beetle species Cosmopolites sordidus and Temnoschoita nigroplagiata are found in the same habitat (banana plantation), they differ with respect to their microhabitat preference and thereby in their risk of being submerged after rain. The physiological characteristics of the two species that might be important in this context were investigated. As expected, C. sordidus is more resistant to submergence (faster recovery, lower mortality: 30% after 9 days submergence at 20 degrees C); this can be attributed to a generally lower metabolic rate, higher glycogen reserves (135 micromol glycosyl units x g FW(-1)) and a moderate lactate production under anoxia. In T. nigroplagiata, the glycogen reserves are almost completely depleted after 1 day submergence at 20 degrees C and a higher proportion of this glycogen can recovered as lactate (16%). During submergence, the adenylate energy charge falls in both species to 0.2 or below, whereas the total adenine nucleotide content decreases only slowly, especially in C. sordidus.

Topics: Adaptation, Physiological; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anaerobic Threshold; Animals; Coleoptera; Energy Metabolism; Environment; Glucose; Glycogen; Hypoxia; Kenya; Lactic Acid; Rain; Species Specificity

Studies with mammals and birds clearly demonstrate that brief preexposure to oxygen deprivation can protect the myocardium from damage normally associated with a subsequent prolonged hypoxic/ischemic episode. However, is not known whether this potent mechanism of myocardial protection, termed preconditioning, exists in other vertebrates including fishes. In this study, we used an in situ trout (Oncorhynchus mykiss) working heart preparation at 10 degrees C to examine whether prior exposure to 5 min of anoxia (PO(2) < or = 5 mmHg) could reduce or eliminate the myocardial dysfunction that normally follows 15 min of anoxic exposure. Hearts were exposed either to a control treatment (oxygenated perfusion) or to one of three anoxic treatments: 1) anoxia with low P(out) [15 min of anoxia at an output pressure (P(out)) of 10 cmH(2)O]; 2) anoxia with high P(out) [10 min of anoxia at a P(out) of 10 cmH(2)O, followed by 5 min of anoxia at P(out) = 50 cmH(2)O]; and 3) preconditioning [5 min of anoxia at P(out) = 10 cmH(2)O, followed after 20 min of oxygenated perfusion by the protocol described for the anoxia with high P(out) group]. Changes in maximum cardiac function, measured before and after anoxic exposure, were used to assess myocardial damage. Maximum cardiac performance of the control group was unaffected by the experimental protocol, whereas 15 min of anoxia at low P(out) decreased maximum stroke volume (V(s max)) by 15% and maximum cardiac output (Q(max)) by 23%. When the anoxic workload was increased by raising P(out) to 50 cmH(2)O, these parameters were decreased further (by 23 and 38%, respectively). Preconditioning with anoxia completely prevented the reductions in V(s max) and Q(max) that were observed in the anoxia with high P(out) group and any anoxia-related increases in the input pressure (P(in)) required to maintain resting Q (16 ml. min(-1). kg(-1)). Myocardial levels of glycogen and lactate were not affected by any of the experimental treatments; however, lactate efflux was sevenfold higher in the preconditioned hearts. These data strongly suggest that 1) a preconditioning-like mechanism exists in the rainbow trout heart, 2) increased anaerobic glycolysis, fueled by exogenous glucose, was associated with anoxic preconditioning, and 3) preconditioning represents a fundamental mechanism of cardioprotection that appeared early in the evolution of vertebrates.

Topics: Analysis of Variance; Animals; Glycogen; Heart; Heart Rate; Hypoxia; Ischemic Preconditioning, Myocardial; Lactates; Models, Cardiovascular; Myocardium; Oncorhynchus mykiss; Perfusion; Stroke Volume

This study investigated whether hypoxic exposure increased muscle buffer capacity (beta(m)) and mechanical efficiency during exercise in male athletes. A control (CON, n=7) and a live high:train low group (LHTL, n=6) trained at near sea level (600 m), with the LHTL group sleeping for 23 nights in simulated moderate altitude (3000 m). Whole body oxygen consumption (VO2) was measured under normoxia before, during and after 23 nights of sleeping in hypoxia, during cycle ergometry comprising 4 x 4-min submaximal stages, 2-min at 5.6 +/- 0.4 W kg(-1), and 2-min 'all-out' to determine total work and VO(2peak). A vastus lateralis muscle biopsy was taken at rest and after a standardized 2-min 5.6 +/- 0.4 W kg(-1) bout, before and after LHTL, and analysed for beta(m) and metabolites. After LHTL, beta(m) was increased (18%, P < 0.05). Although work was maintained, VO(2peak) fell after LHTL (7%, P < 0.05). Submaximal VO2 was reduced (4.4%, P < 0.05) and efficiency improved (0.8%, P < 0.05) after LHTL probably because of a shift in fuel utilization. This is the first study to show that hypoxic exposure, per se, increases muscle buffer capacity. Further, reduced VO2 during normoxic exercise after LHTL suggests that improved exercise efficiency is a fundamental adaptation to LHTL.

Topics: Adaptation, Physiological; Adenosine Triphosphate; Adult; Altitude; Atmosphere Exposure Chambers; Bicycling; Creatine; Exercise Test; Glycogen; Heart Rate; Humans; Hydrogen-Ion Concentration; Hypoxia; Lactic Acid; Male; Muscle, Skeletal; Oxygen Consumption; Phosphocreatine

A study of the hematological parameters, glycogen, glucose, and lactate, and the activity of malate and lactate dehydrogenases was carried out in blood and tissues of fishes submitted to two, four, and six hours of hypoxia and recuperation. Only after 4 h of hypoxia was there a drop in liver glucose. Alter 16 h, a drop in lactate and a rise in glucose in practically all tissues signaled a recuperation of the metabolism, probably due to ASR (aerial surface respiration). Lactate formed during hypoxia was canalized to heart and brain for oxidation and used for neoglucogenesis. There were no changes in hematological parameters nore in the activity of malate and lactate dehydrogenases during normoxia and hypoxia, which suggest that these adaptive mechanisms may not be involved during hypoxia. Glycogen concentrations did not show variation during hypoxia either.

Topics: Alcohol Oxidoreductases; Animals; Carbohydrate Metabolism; Fishes; Glucose; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lactates; Malate Dehydrogenase; Time Factors

The present study examined the acute effects of hypoxia on the regulation of skeletal muscle metabolism at rest and during 15 min of submaximal exercise. Subjects exercised on two occasions for 15 min at 55% of their normoxic maximal oxygen uptake while breathing 11% O(2) (hypoxia) or room air (normoxia). Muscle biopsies were taken at rest and after 1 and 15 min of exercise. At rest, no effects on muscle metabolism were observed in response to hypoxia. In the 1st min of exercise, glycogenolysis was significantly greater in hypoxia compared with normoxia. This small difference in glycogenolysis was associated with a tendency toward a greater concentration of substrate, free P(i), in hypoxia compared with normoxia. Pyruvate dehydrogenase activity (PDH(a)) was lower in hypoxia at 1 min compared with normoxia, resulting in a reduced rate of pyruvate oxidation and a greater lactate accumulation. During the last 14 min of exercise, glycogenolysis was greater in hypoxia despite a lower mole fraction of phosphorylase a. The greater glycogenolytic rate was maintained posttransformationally through significantly higher free [AMP] and [P(i)]. At the end of exercise, PDH(a) was greater in hypoxia compared with normoxia, contributing to a greater rate of pyruvate oxidation. Because of the higher glycogenolytic rate in hypoxia, the rate of pyruvate production continued to exceed the rate of pyruvate oxidation, resulting in significant lactate accumulation in hypoxia compared with no further lactate accumulation in normoxia. Hence, the elevated lactate production associated with hypoxia at the same absolute workload could in part be explained by the effects of hypoxia on the activities of the rate-limiting enzymes, phosphorylase and PDH, which regulate the rates of pyruvate production and pyruvate oxidation, respectively.

Topics: Adenosine Triphosphate; Adult; Carnitine; Coenzyme A; Energy Metabolism; Exercise; Glycogen; Glycolysis; Heart; Humans; Hypoxia; Lactic Acid; Male; Muscle, Skeletal; Phosphates; Phosphorylases; Pyruvate Dehydrogenase Complex; Pyruvic Acid; Respiration

In this study, we compared survivorship, heat dissipation and biochemical features of anaerobiosis of two tiger beetle species (Coleoptera: Cicindelidae) exposed to anoxia. One species commonly experiences environmental immersion from rainfall and snowmelt (Cicindela togata), and the habitat of the other (Amblycheila cylindriformis) is not prone to flooding. The ancestral genus, A. cylindriformis, survives anoxia for only 2 days at 25 degrees C. In response to anoxia, these larvae immediately lose locomotory abilities, tissue concentrations of ATP fall precipitously within 12 h, and significant amounts of lactate are quickly produced. In contrast, C. togata larvae tolerate anoxia for 5 days. Heat dissipation is downregulated to a greater degree than that seen in A. cylindriformis (3.4% versus 14% of standard normoxic rate, respectively), the ability for locomotion is maintained and normoxic levels of ATP are defended for at least 24 h. Lactate is not accumulated until well into anoxic bout, and significant amounts of alanine are also produced. This study provides evidence that tiger beetles differ in physiological responses to anoxia, and that these differences are correlated with flooding risk and with species distribution.

Topics: Adaptation, Physiological; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anaerobiosis; Animals; Coleoptera; Disasters; Energy Metabolism; Environment; Glycogen; Hot Temperature; Hypoxia; Inosine Monophosphate; Lactic Acid; Oxygen; Phylogeny

An intracellular mechanism that senses decreases in tissue oxygen level and stimulates hypoxia-related gene expression has been reported in various cell types including the cardiac cell. The mechanism can also be activated by Co(2+) in normoxia. Thus we investigated the effects of prior chronic oral CoCl(2) on mechanical functions of isolated, perfused rat hearts in hypoxia-reoxygenation. In normoxic rats, 43 days of Co(2+) administration increased hematocrit from 45 +/- 0.3% (control, n = 18) to 51 +/- 0.6% (n = 19). In hypoxia and reoxygenation, Co(2+)-pretreated hearts exhibited a significantly higher rate-pressure product (267 and 163%, respectively) and coronary flow (127 and 118%, respectively) and lower end-diastolic pressure (72 and 60%, respectively) compared with the control hearts. Although the oral Co(2+) administration significantly raised myocardial Co(2+) concentration, it did not affect mitochondrial respiration, tissue glycogen concentration, or myocardial tissue histology. The levels of vascular endothelial growth factor, aldolase-A, and glucose transporter-1 mRNA were significantly elevated in the Co(2+)-treated myocardium. We conclude that cardiac contractile functions would gain hypoxic tolerance when the endogenous cellular oxygen-sensing mechanism is activated.

Topics: Adaptation, Physiological; Animals; Antimutagenic Agents; Cobalt; Coronary Circulation; Dose-Response Relationship, Drug; Energy Metabolism; Glycogen; Heart; Hematocrit; Hypoxia; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Organ Size; Oxygen Consumption; Perfusion; Rats; Rats, Sprague-Dawley; Ventricular Pressure

1. Tonic contraction in response to K+ is well known to be highly dependent on aerobic metabolism in ileal muscle. The ionophore A23187 (10(-5) M) induced an initial contraction and successive rhythmic contraction in ileal muscle, but did not induce tonic contraction. This study, therefore, was performed to investigate the metabolic dependency during contraction induced by A23187. 2. Under hypoxic conditions, A23187 (10(-5) M) induced an initial contraction accompanied by an increase in lactate release. However, it induced only small rhythmic contractions and decreases in ATP, phosphocreatinine (PCr) and glycogen contents. 3. In glucose-free medium, A23187 (10(-5) M) induced an initial contraction and concomitant significant decrease in the ATP and glycogen contents. However, it did not induce successive rhythmic contractions. In 'glycogen-depleted muscle' stimulated repeatedly with 60 mM K+ in glucose-free medium, 60 mM K+ induced a phasic contraction without tonic contraction. A23187 induced no contraction under these conditions. 4. These results suggested that the initial contraction induced by A23187 was dependent on endogenous glycogen, while successive rhythmic contractions were dependent on aerobic metabolism after supply of external glucose to the ileal muscle.

Topics: Adenosine Triphosphate; Animals; Calcimycin; Electric Stimulation; Glucose; Glycogen; Guinea Pigs; Hypoxia; Ileum; Ionophores; Lactose; Male; Muscle Contraction; Muscle, Smooth; Phosphocreatine; Potassium

"Autoresuscitation" (AR) is the spontaneous recovery from hypoxic apnea by gasping. We examined aspects of heart function in two situations: 1) the maturationally acquired failure of AR that is characteristic of SWR, but not BALB/c, weanling mice and 2) AR failure in BALB/c mice induced by repeated exposures to anoxia. We determined maturational changes in heart and liver glycogen. Unlike liver glycogen levels, heart glycogen levels in SWR mice differed from those in BALB/c mice. They were consistently much lower throughout maturation and reached a nadir during the brief period when SWR weanling mice are vulnerable to AR failure. Also, rate of cardiac glycogen utilization in vulnerable SWR mice was lower than that of same-aged BALB/c mice and was nil during the latter one-half of the gasping stage when heart function is critical for AR success. Therefore, because glycogen utilization reflects cardiac work, heart failure could explain AR failure in SWR weanlings. Additionally, the increase in hypoxic heart rate that occurs with maturation is developmentally delayed in SWR mice, and this may contribute to their AR failure. Cardiac glycogen was not fully depleted in BALB/c mice during repeated anoxic exposures, indicating other reasons for AR failure. We view these findings as a potential model for the age-related peak in incidence of sudden infant death syndrome.

Topics: Age Factors; Animals; Apnea; Disease Models, Animal; Glycogen; Heart Rate; Humans; Hypoxia; Infant; Liver Glycogen; Mice; Mice, Inbred BALB C; Myocardium; Resuscitation; Sudden Infant Death

In order to determine the effects of chronic, high-altitude hypoxia on the ovine fetal heart, we exposed pregnant ewes to 3,820 m beginning at 30 days gestation. We previously showed that following approximately 110 days of hypoxia the fetal heart showed significant reduction in cardiac output (76% of control) and contractility, and elevated levels of citrate synthase and lactate dehydrogenase. To investigate ultrastructural influences on these observed physiologic changes at altitude, we hypothesized that the volume densities of myofibrils and mitochondria, and glycogen content would be reduced in the ovine fetal heart and that this may contribute to contraction and cardiac output deficits in hypoxia. Mitochondria and myofibril volume density were determined by standard point-counting techniques and glycogen content was determined by biochemical analysis. The glycogen content from the hypoxic right ventricle (4.8 +/- 0.3%) was significantly lower than in control right ventricle (6.8 +/- 0.5%) and both left ventricles (hypoxia, 7.2 +/- 0.5; control, 7.8 +/- 0. 4%). Total mitochondrial volume density was also significantly reduced following hypoxia (15.5 +/- 0.7%) compared to controls (16.9 +/- 0.4%). As is common in the ovine fetal heart, the myofibril volume density of the right ventricle from both groups was significantly higher than the left ventricle (RV, 58.6 +/- 1.6; LV 54.3 +/- 0.9%). However, it was not different between control and high altitude. In support of our hypothesis, we may speculate that deficits in the quantity of myocyte glycogen and mitochondria contribute to the observed reduction in cardiac output and contractility, despite the upregulation of citrate synthase and lactate dehydrogenase. In contrast, myofibril volume density was unchanged.

Topics: Altitude; Animals; Female; Fetal Heart; Glycogen; Heart Ventricles; Hypoxia; Mitochondria; Myocardium; Myofibrils; Pregnancy; Sheep

Based on the neurotrophic properties of astrocytes in response to ischemia, the current work focuses on the mechanism for cultured astrocytes to adapt to a hypoxic environment. Intracellular glucose levels in primary cultured rat astrocytes exposed to hypoxia fell by 30% within 24 h, in parallel with a decrease in glycogen stores. Glycolytic metabolism was crucial for cell survival during hypoxia, as 2-deoxyglucose resulted in rapid ATP depletion and cell death. The mechanism for maintaining glucose levels under these conditions appeared to be mobilization of glycogen stores, rather than increased extracellular uptake of glucose, as gluconolactone (an inhibitor of beta1-4 amyloglucosidase) induced a rapid fall in cellular ATP in cultures subjected to hypoxia, whereas cytochalasin B was without affect. Addition of cycloheximide diminished the viability of astrocytes in hypoxia, suggesting an obligatory role of de-novo gene expression to respond to hypoxia. Consistently, the results of differential display suggested the induction of glycolytic enzymes, including aldolase A (EC 4.1.2.13), hexokinase II (ATP: D-hexose 6-phosphotransferase, EC 2.7.1.1), and triosephosphate isomerase (EC 5.3.1.1) in the hypoxic culture. Marked induction of these glycolytic enzymes in hypoxic astrocytes was confirmed by Northern blot analysis. These data provide a theoretical basis to understand the ability of astrocytes to tolerate ischemic condition.

Topics: Animals; Animals, Newborn; Antimetabolites; Astrocytes; Blotting, Northern; Cell Survival; Cells, Cultured; Cycloheximide; Deoxyglucose; DNA, Complementary; Enzyme Induction; Enzymes; Fructose-Bisphosphate Aldolase; Gene Expression Regulation; Glucose; Glycogen; Glycolysis; Hexokinase; Hypoxia; Oxygen; Protein Synthesis Inhibitors; Rats; Rats, Sprague-Dawley; RNA; Triose-Phosphate Isomerase

We have previously reported that exercise training is associated with enhanced insulin-stimulated glucose transport activity and inhibited hypoxia-stimulated glucose transport activity in rat epitrochlearis muscle. Here we examine the potential role of muscle glycogen in the inhibited glucose transport response to hypoxia. Three days of swim training (2 x 3 h/day) produce a 100% increase in glycogen and a 70% increase in GLUT-4 in epitrochlearis muscle. Glucose transport after 1 h of hypoxia in muscles from fed exercise-trained (ET) rats is not significantly elevated above basal and is 40% lower than that in muscles from fed sedentary (SED) rats. Glycogen levels after 1 h of hypoxia are reduced by 27 and 64% in muscles from fed ET and fed SED rats, respectively. After 2 h of hypoxia, glucose transport is significantly increased above basal in muscles from fed ET rats, but this response is still 55% lower than that in muscles from fed SED rats. After 2 h of hypoxia, glycogen is reduced by 50 and 83% in muscles from fed ET and fed SED rats, respectively. After a modified overnight fast (approximately 4.5 g of chow), the glucose transport and glycogen responses to 1 h of hypoxia are not significantly different between muscles from ET and SED rats. These findings demonstrate a strong inverse relationship between glycogen and hypoxia-stimulated glucose transport activity and that high levels of glycogen contribute to the inhibited glucose transport response to hypoxia. Furthermore, failure of the overexpression of GLUT-4 after exercise training to enhance the glucose transport response to contraction/hypoxia suggests selective targeting of the additional GLUT-4 to the insulin-responsive pool.

Topics: Animals; Biological Transport; Glucose; Glucose Transporter Type 4; Glycogen; Hypoxia; Male; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Physical Conditioning, Animal; Rats; Rats, Wistar

At high altitude (HA), carbohydrate (CHO) is thought to be the preferred fuel because of its higher yield of ATP per mole of O2. We used indirect calorimetry and D-[6-3H]glucose infusions to determine total CHO and circulatory glucose utilization during exercise in HA-acclimated and sea level (SL) rats. We hypothesized that the percent contribution of CHO to total metabolism (VO2) is determined by exercise intensity relative to an aerobic maximum (% VO2max). HA rats run under hypoxia (FIO2 = 0.12) showed a decrease in VO2max compared with SL (67.55 +/- 1.26 vs. 89.30 +/- 1.23 ml kg-1 min-1). When exercised at 60% of their respective VO2max, both groups showed the same relative use of CHO (38 +/- 3% and 38 +/- 5% of VO2, at the beginning of exercise, in HA and SL, respectively). In both HA and SL, circulatory glucose accounted for approximately 20% of VO2, the balance was provided by muscle glycogen (approximately 18% of VO2). After 20 min at a higher intensity of 80% VO2max, 54 +/- 5% (HA) and 59 +/- 4% (SL) of VO2 was accounted for by CHO. We conclude the following: (i) the relative contributions of total CHO, circulatory glucose, and muscle glycogen do not increase after HA acclimation because the O2-saving advantage of CHO is outweighed by limited CHO stores; and (ii) relative exercise intensity is the major determinant of metabolic fuel selection at HA, as well as at SL.

Topics: Acclimatization; Adenosine Triphosphate; Aerobiosis; Altitude; Animals; Blood Glucose; Calorimetry, Indirect; Dietary Sucrose; Female; Glucose; Glycogen; Hypoxia; Kinetics; Muscle, Skeletal; Oxygen; Physical Exertion; Rats; Rats, Wistar

The effect of hypoxia on the levels of glycogen, glucose and lactate as well as the activities and binding of glycolytic and associated enzymes to subcellular structures was studied in brain, liver and white muscle of the teleost fish, Scorpaena porcus. Hypoxia exposure decreased glucose levels in liver from 2.53 to 1.70 mumol/g wet weight and in muscle led to its increase from 3.64 to 25.1 mumol/g wet weight. Maximal activities of several enzymes in brain were increased by hypoxia: hexokinase by 23%, phosphoglucoisomerase by 47% and phosphofructokinase (PFK) by 56%. However, activities of other enzymes in brain as well as enzymes in liver and white muscle were largely unchanged or decreased during experimental hypoxia. Glycolytic enzymes in all three tissues were partitioned between soluble and particulate-bound forms. In several cases, the percentage of bound enzymes was reduced during hypoxia; bound aldolase in brain was reduced from 36.4 to 30.3% whereas glucose-6-phosphate dehydrogenase fell from 55.7 to 28.7% bound. In muscle PFK was reduced from 57.4 to 41.7% bound. Oppositely, the proportion of bound aldolase and triosephosphate isomerase increased in hypoxic muscle. Phosphoglucomutase did not appear to occur in a bound form in liver and bound phosphoglucomutase disappeared in muscle during hypoxia exposure. Anoxia exposure also led to the disappearance of bound fructose-1,6-bisphosphatase in liver, whereas a bound fraction of this enzyme appeared in white muscle of anoxic animals. The possible function of reversible binding of glycolytic enzymes to subcellular structures as a regulatory mechanism of carbohydrate metabolism is discussed.

Topics: Animals; beta-Galactosidase; Carbohydrate Metabolism; Enzymes; Fishes; Fructose-Bisphosphatase; Glucose; Glycogen; Glycolysis; Hypoxia; Muscles

We have tested the hypothesis that prolonged fetal hypoxemia causes a reduction in glycogenolytic enzyme activities and/or a depletion of fetal glycogen stores. We compared the effects of short (4 h) and prolonged (24 h) periods of reduced maternal uterine blood flow (RUBF) on glycogen content and on the activities of glucose-6-phosphatase (G-6-Pase), glycogen phosphorylase (GPase), and glycogen synthase (GSase) in selected fetal tissues. RUBF was reduced in 10 pregnant sheep at 135 days of gestation (term approximately 146 days) for either 4 h (n = 5) or 24 h (n = 5); 5 other fetuses were used as controls. During RUBF, fetal SaC2 was decreased from 61.6 +/- 3.9 to 22.0 +/- 1.4% at 4 h and to 26.7 +/- 1.2% at 24 h. Hepatic glycogen content was significantly reduced at 4 h of RUBF, but was not reduced further at 24 h. Fetal liver GPase (active and total enzyme activity) and G-6-Pase activities were reduced at 4 h of RUBF but tended to return toward control values at 24 h. Similarly, hepatic GSase activity tended to decrease at 4 h of RUBF, although the reduction was not quite significant (P = 0.08). We conclude that RUBF causes a reduction of fetal glycogen stores and a reduction in G-6-Pase and GPase activity at 4 h. Fetal tissue glycogen contents were not reduced further at 24 h, compared with 4 h of RUBF, which indicates that fetal glycogenolysis is reduced during this time, probably because of the inhibition of GPase and G-6-Pase. It is not known why the activities of these enzymes are reduced during prolonged RUBF, when circulating epinephrine and norepinephrine concentrations are high.

Topics: Animals; Blood Glucose; Cyclic AMP; Fetal Blood; Fetus; Gases; Glucose-6-Phosphatase; Glycogen; Glycogen Synthase; Glycolysis; Hydrogen-Ion Concentration; Hypoxia; Lactic Acid; Liver; Norepinephrine; Osmolar Concentration; Oxygen; Phosphorylases; Sheep

The most rapid age-related decrease in insulin-stimulated glucose uptake in skeletal muscle occurs between 3 and 5 wk of age in rats. Therefore, we studied unstimulated, insulin-stimulated, and in vitro hypoxia-stimulated 2-deoxy-D-[G-3H]glucose (2-DG) uptake in isolated soleus, flexor digitorum brevis (FDB), and epitrochlearis muscles from rats at 21, 28, and 35 days of age. Age-related decrements in insulin- (approximately 40-60%) and hypoxia-stimulated (approximately 50%) 2-DG uptake occurred in all muscles, and most of the decline was evident by 28 days. Unstimulated 2-DG uptake declined significantly with advancing age in the epitrochlearis (73%) and FDB (60%) and tended to decrease in the soleus (38%). The time course and relative magnitude of these decrements were similar under unstimulated, insulin-stimulated, and hypoxic conditions. GLUT-4 protein concentration was unaltered by age in each muscle. These results indicate that a substantial age-related decrement in 2-DG uptake occurs in several limb muscles from rats at 21 vs. 28-35 days by a mechanism that is independent of GLUT-4 levels and not specific for the insulin-dependent pathway.

Topics: Age Factors; Animals; Biological Transport; Blood Glucose; Body Weight; Glucose; Glucose Transporter Type 4; Glycogen; Hypoxia; Insulin; Male; Monosaccharide Transport Proteins; Muscle Proteins; Muscle, Skeletal; Organ Size; Rats

Studies in animal models and humans suggest that myocardium may adapt to chronic or intermittent prolonged episodes of reduced coronary perfusion. Stable maintenance of partial flow reduction is difficult to achieve in experimental models; thus, in vitro cellular models may be useful for establishing the mechanisms of adaptation. Since moderate hypoxia is likely to be an important component of the low-flow state, isolated adult rat cardiac myocytes were exposed to 1% O2 for 48 hours to study chronic hypoxic adaptation. Hypoxic culture did not reduce cell viability relative to normoxic controls but did enhance glucose utilization and lactate production, which is consistent with an anaerobic pattern of metabolism. Lactate production remained transiently increased after restoration of normal O2 tension. Myocyte contractility was reduced (video-edge analysis), as was the amplitude of the intracellular Ca2+ transient (indo 1 fluorescence) in hypoxic cells. Relaxation was slowed and was accompanied by a slowed decay of the Ca2+ transient. These changes were not due to alterations in the action potential. Tolerance to subsequent acute severe hypoxia occurred in cells cultured in 1% O2 and was manifested as a delay in the time to full ATP-depletion rigor contracture during severe hypoxia and enhanced morphological recovery of myocytes at reoxygenation. The latter was still seen after normalization of the data for the prolonged time to rigor, suggesting a multifactorial basis for tolerance. An intervening period of normoxic exposure before subsequent acute severe hypoxia did not result in loss of tolerance but rather increased the delay to subsequent ATP depletion rigor. Cellular glycogen was preserved during chronic hypoxic exposure and increased after the restoration of normal O2 tension. As mitochondrial cytochromes should be fully oxygenated at levels well below 1% O2, hypoxic adaptation may be mediated by a low-affinity O2-sensing process. Thus, adaptations that occur during prolonged periods of moderate hypoxia are proposed to poise the myocyte in a better position to tolerate impending episodes of severe O2 deprivation.

Topics: Action Potentials; Adaptation, Physiological; Adenosine Triphosphate; Animals; Calcium; Cells, Cultured; Coronary Circulation; Coronary Disease; Culture Media; Data Interpretation, Statistical; Glucose; Glycogen; Heart; Humans; Hypoxia; In Vitro Techniques; Lactates; Myocardial Contraction; Myocardium; Oxygen; Rats; Rats, Sprague-Dawley; Time Factors

Topics: Adaptation, Physiological; Adenosine Triphosphate; Animals; Energy Metabolism; Glycogen; Hypoxia; In Vitro Techniques; Kinetics; Lactic Acid; Male; Monitoring, Physiologic; Myocardial Ischemia; Myocardium; Oxygen; Perfusion; Rats; Rats, Sprague-Dawley

The hypothesis was tested that increased partial pressure of oxygen during the plateau (25 to 26 d of incubation for turkeys) and paranatal (27 to 28 d of incubation) stages of incubation may increase survival rates of turkeys from selected genetic lines. Partial pressure of oxygen inside the incubator cabinet was increased to 171 + 3 mm Hg of the barometric pressure during the plateau stage in oxygen consumption and compared to ambient oxygen (152 + 3 mm Hg). Turkey embryos from genetic lines selected for egg production (E) or growth (F) were compared to their respective randombred controls. These genetic lines have previously been shown to differ in egg weight, eggshell conductance, length of incubation period, embryonic gluconeogenesis, and survival rates during late incubation. Blood, liver, heart, and pipping muscle samples were obtained prior to pipping, at internal pipping and external pipping, and at hatching. The blood was analyzed for glucose concentration and the remaining tissues were assayed for glycogen concentrations. Survival rates were determined on approximately 2,200 eggs in each of three independent trials of the experiment. Interactions of oxygen treatment and genetic line were observed for embryonic survival, heart growth, and hepatic glycogen content. The data suggest that the response to increased oxygen tension in selected genetic lines has been diminished. It was concluded that embryos have been altered metabolically by genetic selection and the concomitant increase in mortality of selected lines during the plateau and paranatal stages is not simply the result of shell quality and hypoxia.

Topics: Aging; Animals; Atmospheric Pressure; Blood Glucose; Egg Shell; Environment; Female; Glucose; Glycogen; Heart; Hypoxia; Liver; Muscle, Skeletal; Myocardium; Organ Size; Oxygen; Poultry Diseases; Survival Rate; Turkeys

Effect of exposure to acute hypoxia and hypoxia for 2 weeks on the skin temperature and content of glycogen of frostbitten feet in rabbits were observed. The results showed that the skin temperatures and content of glycogen were decreased in frostbite at normoxia (FN) group frostbite during acute hypoxia (FAH) group and frostbite hypoxia for 2 weeks (FH-2w) group. After treatment with warm chlorhexidine immersion the skin temperature and glycogen content in treated feet of FN and FAH group were increased, as compared with untreated feet. However, there was no difference between treated and untreated feet in FH-2w group, suggesting that there may be severe disturbance of blood circulation on frostbitten feet under this condition.

Topics: Animals; Frostbite; Glycogen; Hypoxia; Male; Muscle, Skeletal; Rabbits; Skin Temperature

The effect of chronic hypoxia on neonatal myocardial metabolism remains undefined. With a new neonatal piglet model, we determined changes in myocardial metabolism during global ischemia after chronic hypoxia. Five-day-old piglets (N = 30) were randomly assigned to two groups and exposed to an atmosphere of 8% oxygen or to room air for 28 days before they were killed. Left ventricular myocardium was then analyzed at control and at 15-minute intervals during 60 minutes of global normothermic ischemia to determine high-energy phosphate levels, glycogen stores, and lactate accumulation. Time to peak ischemic myocardial contracture was measured with intramyocardial needle-tipped Millar catheters as a marker of the onset of irreversible ischemic injury. Results showed an initially greater level of myocardial adenosine triphosphate in the hypoxic group (27 +/- 1.2 vs 19 +/- 1.8 micromol/gm dry wt, p = 0.001) and a delay in adenosine triphosphate depletion during 60 minutes of global ischemia compared with the control group. Initial energy charge ratios (1/2 adenosine diphosphate + adenosine triphosphate/adenosine monophosphate + adenosine diphosphate + adenosine triphosphate) were also greater in the hypoxic group (0.96 +/- 0.01 vs 0.81 +/- 0.04, p = 0.01) and remained so throughout global ischemia. Initial glycogen stores were greater in the hypoxic group (273 +/- 13.3 vs 215 +/- 14.7 micromol/gm dry weight, p = 0.02) when compared with the control group. Lactate levels in the hypoxic group were initially higher (19.1 +/- 6.4 vs 8.9 +/- 3.1 micromol/gm dry weight, p = 0.001) compared with control levels and remained elevated throughout 60 minutes of ischemia. Time to peak ischemic contracture was prolonged in the hypoxic group (69.5 +/- 1.8 vs 48.9 +/- 1.4 minutes, p = 0.001) compared with the controls group. These data show that chronic hypoxia results in significant myocardial metabolic adaptive changes, which in turn result in an improved tolerance to severe normothermic ischemia. These beneficial effects are associated with elevated baseline glycogen storage levels and an accelerated rate of anaerobic glycolysis during ischemia.

Topics: Animals; Animals, Newborn; Chronic Disease; Disease Models, Animal; Glycogen; Hypoxia; Myocardial Contraction; Myocardium; Swine; Ventricular Function, Left

During hypoxia, the heart consumes glycogen to generate ATP. Tolerance of repetitive hypoxia logically requires prompt replenishment of glycogen, a process whose regulation is not fully understood. To examine this, we imposed a defined hypoxic stimulus on the rat heart while varying its workload. In intact rats, hypoxia reduced myocardial glycogen approximately 30% and increased both the fraction of glycogen synthase in its physiologically active (GS I) form (from 0.24 +/- 0.06 to 0.82 +/- 0.07; P < 0.005) and glycogen synthesis (from 0.087 +/- 0.011 to 0.375 +/- 0.046 mumol.g-1.min-1; P < 0.005). Reducing cardiac work (with propranolol or heterotopic transplantation) reduced glycogen breakdown, glycogen synthase activation, and glycogen synthesis in parallel, stepwise fashion in intact rats. Correspondingly, hypoxia increased GS I activity in the perfused heart in vitro, but only under conditions where glycogen was consumed. This suggests myocardial glycogen synthase is activated by systemic hypoxia and catalyzes rapid posthypoxic glycogen synthesis. Hypoxic glycogen synthase activation appears to be a proportionate, wholly intrinsic response to local glycogenolysis, operating to preserve myocardial glycogen stores independent of any extracardiac mediator of carbohydrate metabolism.

Topics: Animals; Blood Pressure; Gases; Glucose-6-Phosphate; Glycogen; Glycogen Synthase; Heart Rate; Heart Transplantation; Homeostasis; Hypoxia; Insulin; Male; Myocardial Contraction; Myocardium; Osmolar Concentration; Oxygen; Propranolol; Rats; Rats, Sprague-Dawley

To determine the fate of lactate during and after prolonged anoxia, 14C-labeled lactate was injected into turtles after 2 h of a 6-h submergence at 20 degrees C. 14C activities of plasma and chamber water were tested at intervals during anoxia and also in expired air during 39 h of recovery. Partitioning of label in major body compartments [extracellular fluid (ECF), intracellular fluid (ICF), and shell] and 14C activity and glycogen in selected tissues (heart, liver, and muscle) were measured after anoxia (n = 7) and after recovery (n = 6). Shell 14C and [lactate] were extensively measured on six anoxic turtles. During anoxia all 14C remained in the animal indicating no urine production. At 6 h of anoxia 47% of recovered 14C, presumably still as lactate, was in the ECF, 27% in the ICF, and 30% in the shell. During recovery, plasma [lactate] fell from 35 to 5 meq, but surrounding water and expired air accounted for only 9 and 8%, respectively, of recovered label. The ICF portion grew to 41%, associated with a recovery in tissue glycogen. The shell still had 22% of total label. We conclude that, during recovery from anoxia, lactate is predominantly resynthesized to glycogen, and only a small fraction is directly oxidized. During anoxia, however, lactate is widely distributed in the body, and a surprisingly large and functionally significant fraction resides in the shell.

Topics: Animals; Carbon Dioxide; Carbon Radioisotopes; Extracellular Space; Glycogen; Hypoxia; Lactic Acid; Liver; Muscles; Myocardium; Respiration; Tissue Distribution; Turtles

In isovolumically perfused Langendorff heart preparations of guinea pigs adenosine-depending on the experimental protocol-more or less could prevent the hypoxia-induced decrease in myocardial adenosine triphosphate [ATP], creatine phosphate [CP], glycogen and increase in lactate, i.e. showed cardioprotection.

Topics: Adenosine; Adenosine Triphosphate; Animals; Glycogen; Guinea Pigs; Heart; Hypoxia; In Vitro Techniques; Lactic Acid; Myocardium; Phosphocreatine; Reference Values

Hypobaric hypoxia at one-half atmospheric pressure for 3 wk was reported to increase the brain capillary density and glucose transport at the blood-brain barrier in the adult rat. We examined the metabolic concomitants of these alterations in rats subjected to the same hypoxic insult. Hypoxic rats increased brain glucose and lactate concentrations and decreased brain glycogen. However, hypoxia had no significant effects on regional brain levels of ATP and phosphocreatine or on intracellular pH, indicating successful adaptation to the hypoxic insult. 2-Deoxyglucose studies showed that hypoxia increased the regional metabolic rate for glucose by 10-40%. These results indicate increased glycolysis in the hypoxic rat brain, which probably underlies the increased density of glucose transporters in brain microvessels and the increased blood-to-brain glucose influx in hypoxia.

Topics: Adenosine Triphosphate; Animals; Atmospheric Pressure; Brain; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Male; Phosphocreatine; Rats; Rats, Wistar; Reference Values

Freshwater turtles Trachemys scripta elegans endure prolonged severe hypoxia, and even complete anoxia, while diving or hibernating underwater. Metabolic adaptations supporting survival include the activation of glycogenolysis and glucose output from liver, as well as strong metabolic rate depression. The present study analyzes the enzymes of both the phosphorolytic (glycogen phosphorylase, phosphorylase b kinase, cAMP-dependent protein kinase) and glucosidic (alpha-glucosidase) pathways of glycogenolysis in turtle organs. Turtles were subjected to 5 hr of submergence in N2-bubbled water at 7 degrees C and then activities of phosphorolytic and glucosidic enzymes were assayed in liver, heart, brain, and red and white skeletal muscle, and compared with aerobic controls. In vitro incubations also assessed protein kinase A control of phosphorolytic enzymes. A functional enzyme cascade system for the activation of glycogen phosphorylase was found in all organs, and both phosphorylase and phosphorylase kinase were stimulated by in vitro incubation with the catalytic subunit of cAMP-dependent protein kinase. Anoxic submergence led to significant increases in phosphorylase activities in liver and heart (phosphorylase a rose 2- and 2.5-fold, respectively) but phosphorylase kinase and protein kinase A activities in liver were reduced after 5 hr exposure. Both acidic (pH 4) and neutral (pH 7) forms of alpha-glucosidase were detected in all five organs with highest activities in liver. Activity of acid alpha-glucosidase, which degrades lysosomal glycogen, increased by 2-fold in liver during anoxic submergence. The data show that glycogen breakdown in turtle liver during anoxic submergence may result from coordinated activations of both the cytoplasmic phosphorolytic and the lysosomal glucosidic pathways of glycogenolysis.

Topics: Adaptation, Physiological; alpha-Glucosidases; Animals; Cyclic AMP-Dependent Protein Kinases; Diving; Glucosyltransferases; Glycogen; Hibernation; Hydrolysis; Hypoxia; Immersion; Organ Specificity; Phosphorylation; Turtles

The role of calmoudulin in control of carbohydrate metabolism in the absence and presence of insulin in isolated mouse soleus muscle was investigated. The calmodulin antagonist CGS 9343B had no effect on basal glycogen synthase activity, the contents of high energy phosphates, glucose-6-P, or glycogen synthesis. However, CGS 9343B inhibited the basal rates of 2-deoxyglucose uptake and 3-O-methylglucose transport by 30% (p < 0.05) and 40% (p < 0.001), respectively. Insulin activated glycogen synthase by almost 40% (p < 0.01) and this increase was not altered in the presence of CGS 9343B. Insulin increased the muscle content of glucose-6-P (approximately equal to 2-fold), as well as glycogen synthesis (approximately equal to 8-fold), 2-deoxyglucose uptake (approximately equal to 3-fold), and 3-O-methylglucose transport (approximately equal to 2-fold), and these increases were inhibited by CGS 9343B. In additional experiments on isolated rat epitrochlearis muscle, it was found that the hypoxia-mediated activation of 3-O-methylglucose transport was also inhibited by CGS 9343B. These data demonstrate that: 1) hexose transport, both in the absence and presence of external stimuli (insulin and hypoxia), requires functional calmodulin; and 2) insulin-mediated activation of glycogen synthase does not require functional calmodulin, nor can it be accounted for by increases in glucose transport or glucose-6-P.

Topics: 3-O-Methylglucose; Animals; Benzimidazoles; Biological Transport; Calmodulin; Deoxyglucose; Dose-Response Relationship, Drug; Enzyme Activation; Glycogen; Glycogen Synthase; Hypoxia; In Vitro Techniques; Insulin; Male; Methylglucosides; Mice; Muscle, Skeletal; Rats

The energy metabolism was evaluated in gastrocnemius muscle from 3-month-old rats subjected to either mild or severe 4-week intermittent normobaric hypoxia. Furthermore, 4-week treatment with CNS-acting drugs, namely, alpha-adrenergic (delta-yohimbine), vasodilator (papaverine, pinacidil), or oxygen-increasing (almitrine) agents was performed. The muscular concentration of the following metabolites was evaluated: glycogen, glucose, glucose 6-phosphate, pyruvate, lactate, lactate-to-pyruvate ratio; citrate, alpha-ketoglutarate, succinate, malate; aspartate, glutamate, alanine; ammonia; ATP, ADP, AMP, creatine phosphate. Furthermore the Vmax of the following muscular enzymes was evaluated: hexokinase, phosphofructokinase, pyruvate kinase, lactate dehydrogenase; citrate synthase, malate dehydrogenase; total NADH cytochrome c reductase; cytochrome oxidase. The adaptation to chronic intermittent normobaric mild or severe hypoxia induced alterations of the components in the anaerobic glycolytic pathway [as supported by the increased activity of lactate dehydrogenase and/or hexokinase, resulting in the decreased glycolytic substrate concentration consistent with the increased lactate production and lactate-to-pyruvate ratio] and in the mitochondrial mechanism [as supported by the decreased activity of malate dehydrogenase and/or citrate synthase resulting in the decreased concentration of some key components in the tricarboxylic acid cycle]. The effect of the concomitant pharmacological treatment suggests that the action of CNS-acting drugs could be also related to their direct influence on the muscular biochemical mechanisms linked to energy transduction.

Topics: Adenine Nucleotides; Almitrine; Animals; Chronic Disease; Energy Metabolism; Glycogen; Glycolysis; Guanidines; Hypoxia; Male; Mitochondria, Muscle; Muscle, Skeletal; Papaverine; Pinacidil; Rats; Rats, Wistar; Stereoisomerism; Time Factors; Vasodilator Agents; Yohimbine

Topics: Adaptation, Physiological; Animals; Energy Metabolism; Female; Glycogen; Hypoxia; Microscopy, Electron; Myocardium; Pregnancy; Rats; Rats, Wistar

Working rat hearts perfused with 5.5 mM glucose were submitted to a 10-min period of no-flow ischaemia or anoxia. Both conditions stimulated glycogenolysis, activated phosphorylase and increased cyclic GMP content, although the time course of these changes differed in anoxia and ischaemia. Changes in cyclic GMP content were not correlated with glycogenolysis or phosphorylase activation. Perfusion with 1 microM L-nitroarginine methylester, an inhibitor of nitric oxide synthase, decreased cGMP concentration under normoxic conditions and abolished the ischaemia-induced increase in cGMP. The inhibitor decreased the coronary flow without affecting the overall working performance of the hearts under normoxic conditions.

Topics: Adenosine Triphosphate; Amino Acid Oxidoreductases; Animals; Arginine; Coronary Circulation; Cyclic GMP; Fructosediphosphates; Glucose; Glycogen; Heart; Hexosephosphates; Hypoxia; In Vitro Techniques; Kinetics; Male; Myocardial Ischemia; Myocardium; NG-Nitroarginine Methyl Ester; Nitric Oxide Synthase; Perfusion; Rats; Rats, Wistar; Time Factors

It has recently been shown that hypoxia and ischemia are equally effective to precondition the myocardium of the rat. A comparison of the metabolic changes caused by transient ischemia and hypoxia has not yet been made and may help to elucidate the metabolic factors involved in eliciting preconditioning. The aim of this study was to compare the changes in tissue high energy phosphates, glycogen and lactate during and after hypoxic and ischemic preconditioning in isolated perfused rat hearts. Isolated rat hearts were subjected to global ischemia of 30 minutes duration, with and without preconditioning consisting of a single episode of 5 minutes global ischemia or hypoxia (PO2 = 12kPa). The post-ischemic recovery of aortic flow of the nonpreconditioned group was significantly less than that of the two preconditioned groups: 0.5 +/- 0.5 ml/min vs. 23.3 +/- 3.4 and 20.7 +/- 3.6 ml/min for ischemic and hypoxic preconditioning respectively. The only common metabolic factor between the two preconditioned groups was the similar extent of glycogenolysis after transient ischemia or hypoxia: glycogen decreased from 22 +/- 0.8 in non-preconditioned hearts to 16 +/- 0.5 and 16 +/- 1.5 mumoles glucose per g wet tissue in ischemic and hypoxic preconditioned hearts respectively. There was also no difference in lactate production between the two groups during the sustained episode of ischemia. We conclude that oxygen deprivation, rather than other metabolic factors, is the important factor in eliciting preconditioning.

Topics: Animals; Coronary Circulation; Glycogen; Hypoxia; Lactates; Male; Models, Biological; Myocardial Ischemia; Perfusion; Phosphates; Rats; Rats, Wistar; Reperfusion

The aim of present work was to study the cardioprotective effect of the potassium channel opener levcromakalim at a low concentration (0.3 microM) which does not depress heart rate and left ventricular developed pressure. For the determination of the protection against 10 or 20 min duration of hypoxia (95% N2 + 5% CO2) in isovolumically-perfused Langendorff heart preparations of guinea-pigs biochemical parameters (ATP, phosphocreatine, lactate and glycogen) were used. Under normoxic (95% O2 + 5% CO2) conditions 0.3 microM levcromakalim has not changed myocardial high energy phosphates, glycogen, lactate and the hypoxia induced decrease in ATP and phosphocreatine. The 10 min hypoxia induced increase in lactate and decrease in glycogen have--slightly but not significantly--been moderated and when the duration of hypoxic perfusion has lasted 20 min, this protection became significant. It is supposed that the preservation of glycogen stores induced by levcromakalim may contribute to the decrease of intracellular acidosis evoked by hypoxia. Therefore--in such experimental condition-, this mechanism may constitute the biochemical basis of cardioprotective effect of levcromokalim.

Topics: Adenosine Triphosphate; Animals; Antihypertensive Agents; Benzopyrans; Cardiotonic Agents; Cromakalim; Energy Metabolism; Glycogen; Guinea Pigs; Heart; Hypoxia; In Vitro Techniques; Lactates; Myocardium; Phosphocreatine; Pyrroles

Functional recovery following ischemia and reperfusion in the isolated working rat heart perfused with glucose (11 mM) was examined in relation to pre- and postischemic levels of ATP, glycogen, glucose 6-phosphate, and the lactate-to-pyruvate ratio. The following variables were studied: feeding and fasting in vivo, addition of L-lactate (10 mM), dl-beta-hydroxybutyrate (10 mM), glucagon (0.01 and 1 micrograms/ml), and a 15-min anoxic perfusion before ischemia in vitro. Recovery was assessed as the percentage of preischemic power. Good correlation was found between functional recovery and the postischemic content of glycogen. Glycogen depletion by anoxia or glucagon before ischemia impaired recovery. There was no relationship among lactate produced, or the lactate-to-pyruvate ratio, and recovery. The addition of lactate or beta-hydroxybutyrate to hearts from fed rats increased the content of glycogen and glucose 6-phosphate, whereas addition of lactate, but not beta-hydroxybutyrate, improved recovery. There was a linear relationship between glycogen content and glucose 6-phosphate levels. In conclusion, the degree of return of oxidative metabolism and of net glycogen resynthesis reflects postischemic recovery of function. The results also suggest a role for anaplerosis of the citric acid cycle as an additional determinant of postischemic recovery.

Topics: 3-Hydroxybutyric Acid; Adenosine Triphosphate; Animals; Fasting; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Heart; Hydroxybutyrates; Hypoxia; In Vitro Techniques; Lactates; Lactic Acid; Male; Myocardial Contraction; Myocardial Ischemia; Myocardial Reperfusion; Myocardium; Pyruvates; Pyruvic Acid; Rats; Time Factors

The level of systemic hypoxia required to alter neonatal myocardial metabolism and its resultant effect on tolerance to global ischemia is unknown. This study examines myocardial purine nucleotides, glycogen (MG), lactate, creatine phosphate (CP) and the subsequent tolerance to ischemia in hearts exposed to varying levels of hypoxia (2 h). Three-day-old swine were randomly allocated into five study groups. Animals were anaesthetized and ventilated (2 h) with varying mixtures of medical air and nitrogen to achieve their target PaO2 (mmHg): normoxia (PaO2 = 80, n = 18), mild (PaO2 = 60, n = 10), moderate (PaO2 = 40, n = 12), moderately-severe (PaO2 = 30, n = 7) and severe (PaO2 = 20, n = 9). Arterial blood gases verified PaO2 and normal PaCO2 (39.5 +/- 0.5 mmHg). Subsequently, the heart was exposed and the metabolic profile determined from a freeze-clamp LV biopsy. The heart was excised and tolerance to ischemia determined by time (min) to ischemic contracture onset (TICo) and peak (TICp). The results demonstrated a tendency to decreased MG with progressive hypoxia which reached significance in severe hypoxia (6.6 +/- 2.7 mumol/g, P < 0.05). Despite a doubling of myocardial lactate with moderately-severe hypoxia, increases only reached significance with severe hypoxia (27.8 +/- 6.3 mumol/g, P < 0.0001). Despite the reduction in LV adenosine triphosphate (ATP) with severe hypoxia (2.16 +/- 0.68 mumol/g, P < 0.05), CP was unaltered.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Animals, Newborn; Blood Gas Analysis; Glycogen; Hypoxia; Inosine Monophosphate; Lactates; Male; Myocardial Ischemia; Myocardium; Phosphocreatine; Severity of Illness Index; Swine; Time Factors

GLUT4 glucose transporter content and glucose transport capacity are closely correlated in skeletal muscle. In this study, we tested the hypothesis that a rapid increase in GLUT4 expression occurs as part of the early adaptive response of muscle to exercise and serves to enhance glycogen storage. Rats exercised by swimming had a approximately 2-fold increase in GLUT4 mRNA and a 50% increase in GLUT4 protein expression in epitrochlearis muscle 16 h after one prolonged exercise session. After a 2nd day of exercise, muscle GLUT4 protein was increased further to approximately 2-fold while there was no additional increase in GLUT4 mRNA. Muscle hexokinase activity also doubled in response to 2 days of exercise. Glucose transport activity maximally stimulated with insulin, contractions, or hypoxia was increased roughly in proportion to the adaptive increase in GLUT4 protein in epitrochlearis muscles. Treatment with insulin prior to subcellular fractionation of muscle resulted in a approximately 2-fold greater increase in GLUT4 content of a plasma membrane fraction in the 2-day swimmers than in controls. When epitrochlearis muscles were incubated with glucose and insulin, glycogen accumulation over 3 h was twice as great in muscles from 2-day swimmers as in control muscles. Our results show that a rapid increase in GLUT4 expression is an early adaptive response of muscle to exercise. This adaptation appears to be mediated by pretranslational mechanisms. We hypothesize that the physiological role of this adaptation is to enhance replenishment of muscle glycogen stores.

Topics: 3-O-Methylglucose; Actins; Animals; Deoxyglucose; Female; Glucose; Glucose Transporter Type 4; Glycogen; Hypoxia; Insulin; Kinetics; Methylglucosides; Monosaccharide Transport Proteins; Muscle Contraction; Muscle Proteins; Muscles; Physical Conditioning, Animal; Rats; Reference Values; RNA, Messenger; Time Factors

To examine the role of Na+/H+ exchange in cardiac injury, we compared the effect of amiloride (174 microM) with the markedly more specific and potent inhibitor 5-(N,N-hexamethylene) amiloride (HMA, 1 microM) against cardiac injury produced by reperfusion, reoxygenation, and the calcium paradox. Reperfusion after 15-min ischemia resulted in a 55 +/- 4% recovery in contractility, whereas in the presence of amiloride or HMA, recovery was increased to 82 +/- 5.8 and 72 +/- 7.8%, respectively (p < 0.05 from control), with HMA showing particular efficacy in accelerating recovery. The rapid restoration of function with HMA was also evident in hearts reoxygenated for 1 min after 12-min hypoxia (control 35 +/- 3.2%, HMA 66 +/- 4.1%, p < 0.05) although the protective effect gradually reversed with continued reoxygenation. On the other hand, with addition of amiloride, the protective effect persisted so that after 30-min reoxygenation values were significantly higher than control (65 +/- 4.1 vs. 47 +/- 3.1%, p < 0.05). Resting tension increases after either reperfusion or reoxygenation were moderate: 124 +/- 8 and 119 +/- 6%, respectively (p > 0.05), but no increases were observed with amiloride or HMA. Bepridil (10 microM), a purported Na+/Ca2+ exchange inhibitor, exerted a salutary effect against reperfusion dysfunction identical to that of amiloride and HMA, whereas in reoxygenated hearts the effects were identical to those observed with HMA. The protective effects of the drugs were not related to improved energy metabolic status. None of the pharmacologic interventions exerted beneficial effects against the calcium paradox.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Amiloride; Animals; Bepridil; Calcium; Carrier Proteins; Glycogen; Heart; Heart Rate; Hydrogen; Hypoxia; In Vitro Techniques; Male; Myocardial Contraction; Myocardial Reperfusion Injury; Myocardium; Rats; Rats, Sprague-Dawley; Sodium; Sodium-Hydrogen Exchangers

Medicinal leeches (Hirudo medicinalis L.) responded to self-induced hypoxia (72 h) with typical anaerobic metabolism characterized by a decrease in adenylate energy charge, utilization of the substrates glycogen and malate, and accumulation of the main anaerobic end-products succinate and propionate. Propionate was also excreted into the medium. Ammonia excretion was suppressed. Aerobic recovery resulted in a profound O2 debt. Resynthesis of ATP was completed within 30 min. Disposal of succinate and restoring of malate required 2-3 h, and clearance of propionate and recharging of glycogen 6-12 h. Ammonia excretion did not exceed normoxic rates and excretion of propionate during recovery accounted for only 10% of total propionate accumulated during hypoxia. It is postulated that the clearance of succinate and propionate involves oxidation but also resynthesis of malate and glycogen. During hypoxia and recovery blood osmolality remained constant. The Na+ and Cl- ion concentrations in blood, the decrease of which was nearly equimolar during hypoxia, were re-established following different time-courses. Na+ concentration returned to normoxic levels after 2-3 h. The delayed increase in Cl- concentration, however, correlating with 6-12 h necessary to clear blood propionate, is interpreted as an anion regulating effect.

Topics: Acetates; Acetic Acid; Adenine Nucleotides; Anaerobiosis; Animals; Chlorides; Glycogen; Hypoxia; Kinetics; Leeches; Oxygen Consumption; Propionates; Sodium; Water-Electrolyte Balance

Two groups of young broiler chickens, namely, naturally occurring field cases of ascites and those with an induced hypoxia, were used in an ultrastructural study to examine the localisation and distribution of intracellular Ca2+ in cardiomyocytes. Age-matched healthy flockmates were used to control each group. Deposits of Ca2+ were located extensively in the mitochondria, sarcoplasmic reticulum and Golgi apparatus and sometimes in the myocyte and endothelial cell nuclei of both groups of birds. The results suggest that the cells from the hearts of the ascitic broilers may have been exposed to hypoxia since a large proportion of control material showed no Ca2+ activity in either mitochondria or nuclei. The presence of a Ca2+ overload in the mitochondria of cardiomyocytes from ascitic birds reared at low altitude or sea level suggests that these broilers were suffering from the deleterious effects of chronic hypoxia due to poor or reduced oxygen use.

Topics: Animals; Ascites; Calcium; Chickens; Endoplasmic Reticulum; Glycogen; Golgi Apparatus; Hypoxia; Male; Microscopy, Electron; Mitochondria, Heart; Myocardium; Reference Values

Stimulation of skeletal muscle to contract activates phosphorylase b-to-a conversion and glycogenolysis. Despite reversal of the increase in percentage of phosphorylase a after a few minutes, continued glycogen breakdown can occur during strenuous exercise. Hypoxia causes sustained glycogenolysis in skeletal muscle without an increase in percentage of phosphorylase a. We used this model to obtain insights regarding how glycogenolysis is mediated in the absence of an increase in percentage of phosphorylase a. Hypoxia caused a 70% decrease in glycogen in epitrochlearis muscles during an 80-min incubation despite no increase in percentage of phosphorylase a above the basal level of approximately 10%. Muscle Pi concentration increased from 3.8 to 8.6 mumol/g muscle after 5 min and 15.7 mumol/g after 20 min. AMP concentration doubled, attaining a steady state of 0.23 mumol/g in 5 min. Incubation of oxygenated muscles with 0.1 microM epinephrine induced an approximately sixfold increase in percentage of phosphorylase a but resulted in minimal glycogenolysis. Muscle Pi concentration was not altered by epinephrine. Despite no increase in percentage of phosphorylase a, hypoxia resulted in a fivefold greater depletion of glycogen over 20 min than did epinephrine. To evaluate the role of phosphorylase b, muscles were loaded with 2-deoxyglucose 6-phosphate, which inhibits phosphorylase b. The rate of glycogenolysis during 60 min of hypoxia was reduced by only approximately 14% in 2-deoxyglucose 6-phosphate-loaded muscles.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Monophosphate; Animals; Epinephrine; Glucose-6-Phosphate; Glucosephosphates; Glycogen; Hypoxia; Inosine Monophosphate; Male; Muscles; Osmolar Concentration; Phosphorus; Phosphorylase a; Phosphorylase b; Rats; Rats, Wistar

Quechuas and Sherpas have long attracted the interest of high altitude biology and medicine. From our current knowledge, it appears that three of their most impressive high altitude adaptations are (i) high efficiency performance even in hypobaric hypoxia, (ii) low maximum (aerobic and anaerobic) capacities, and (iii) high endurance (the latter being less well documented, but widely accepted). Muscle biopsy and enzyme activity measurements clarify the basis for at least some of these adaptations. Firstly, low activity levels of enzymes in oxidative metabolism (comparable to power athletes) predict low VO2max capacities, as previously observed. Secondly, anaerobic glycolytic capacities also are low (comparable to endurance athletes) which explains low anaerobic work capacities. Thirdly, the glycolytic pathway is seemingly organized for carbohydrate oxidation, not fermentation. Because glucose (glycogen) metabolism uses O2 efficiently, the endurance characteristic may arise from coupling carbohydrate-based adenosine triphosphate (ATP) synthesis with efficient pathways of ATP utilization (for high yield of muscle work/ATP).

Topics: Adaptation, Physiological; Altitude; Animals; Birds; China; Glycogen; Humans; Hypoxia; Indians, South American; Muscles; Oxygen Consumption; Physical Endurance; Rats

Glycogen consumption was investigated in isolated adult rat myocytes incubated for 2 h (37 degrees C) in substrate-free, hypoxic Krebs-Henseleit bicarbonate buffer. No consumption of glycogen occurred after 1 h of incubation, and the residual glycogen after 2 h was 23% despite an 89% reduction of the initial ATP content (from 27.1 +/- 1.8 to 3.1 +/- 0.5 nmol/mg dry weight, n = 12). The residual glycogen was not due to lactate inhibition of glycolytic enzymes, since myocytes incubated in the presence of 5 mM glucose maintained high energy phosphates throughout the incubation period despite a considerable lactate accumulation (1740 +/- 43 nmol/mg dry weight in glucose-supplemented vs. 138 +/- 14 nmol/mg dry weight in substrate-free incubations, n = 12). We have previously shown that the content of cyclic AMP in myocytes is not altered in response to hypoxia, thereby excluding activation of glycogen phosphorylase a. In the present study, the fall in myocyte ATP content was not followed by a rise in AMP, possibly preventing allosteric activation of glycogen phosphorylase b. However, addition of cyanide to the hypoxic incubations increased cellular AMP (initial level 2.1 +/- 0.4 nmol/mg dry weight vs. 9.8 +/- 0.7 after 30 min, n = 12) without increasing the amount of glycogen consumed, also ruling out the lack of glycogen phosphorylase b activation in the myocytes. Therefore, the glycogen rest was probably confined to the 17% of myocytes hypercontracted at the start of incubations.

Topics: Adenine Nucleotides; Animals; Cyanides; Glycogen; Glycolysis; Hypoxia; In Vitro Techniques; Lactates; Male; Myocardium; Phosphates; Phosphorylases; Rats; Rats, Inbred Strains; Sarcolemma

The acute secretion of glucocorticoids is critical for responding to physiological stress. Under normal circumstances these hormones do not cause acute neuronal injury, but they have been shown to enhance ischemic and seizure-induced neuronal injury in the rat brain. Using fetal rat hippocampal cultures, we asked whether hypoxic and hypoglycemic cell damage in vitro could be exacerbated by direct exposure to corticosterone (CORT). Each of these insults alone damaged neuronal cells, whereas 4-6 h of hypoxic treatment could damage age-matched astrocytes if glucose was reduced or omitted. Ischemic-like injury to both cell types could be attenuated by pretreatment with high (30 mM) glucose. Exposure to 100 nM CORT did not affect cell viability under control conditions but enhanced both hypoxic and hypoglycemic neuronal injury. In both cases, pretreatment with high glucose abolished this CORT-mediated synergy. In astrocyte cultures, CORT exacerbated both hypoxic and hypoglycemic injury and this effect was also attenuated by high-glucose pretreatment. Identical 24-h CORT treatment caused a 13% reduction in glucose uptake in astrocytes and a 38% reduction in glycogen content, without affecting the level of intracellular glucose. Thus, CORT could endanger both neurons and astrocytes in mixed hippocampal cultures and this effect emerged only under conditions of substrate depletion. The metabolic disruption in astrocytes by CORT further suggests that the ability of CORT to exacerbate neuronal injury may be due in part to impaired glial cell function.

Topics: Animals; Astrocytes; Biological Transport; Cells, Cultured; Corticosterone; Energy Metabolism; Glucose; Glycogen; Hippocampus; Hypoglycemia; Hypoxia

A defect in isolated perfused rat-liver (IPRL) preparations has been proposed to explain discrepancies between in vivo and in vitro findings regarding hepatic glucose metabolism. The aim of the present study was to investigate whether a preparation of IPRL using a synthetic hemoglobin-free perfusate was capable of net glucose uptake and glycogen deposition at physiological portal substrate concentrations. Livers from fed anaesthetized rats were perfused in a recirculating system using a fluorocarbon emulsion as artificial oxygen carrier. Depending on the prevailing glucose concentration, livers exhibited net glucose uptake or release with a threshold value of 5.5-6.0 mM glucose. Net glucose uptake was associated with net glycogen deposition (+0.23 to +0.59 mumol C6 min-1 g-1). From 5.8 mM (n = 3) and 10.0 mM (n = 8), initial concentration glucose levels fell to 5.3 +/- 0.2 mM after 210 min (n = 3) and 6.3 +/- 0.9 mM after 120 min (n = 8), respectively. This was equivalent to a net glucose uptake of -0.16 and -0.45 mumol min-1 g-1. Anoxia reversibly switched hepatic glucose balance from net uptake (-0.42 mumol min-1 g-1) to release (+0.69 mumol min-1 g-1) followed by net uptake (-0.50 mumol min-1 g-1) after reinstitution of aerobic conditions. We conclude that the composition of perfusion media might play a pivotal role for studies of glucose metabolism in the isolated perfused rat liver. In our experimental model, using a hemoglobin-free synthetic medium, net glucose uptake was readily demonstrated at physiological portal substrate concentrations similar to the in vivo situation.

Topics: Aerobiosis; Animals; Blood Substitutes; Fluorocarbons; Glucose; Glycogen; Hypoxia; Liver; Male; Oxygen; Perfusion; Portal System; Rats; Rats, Inbred Strains

Repeated phases of hypoxia (8 h daily for 2 to 5 days at pO2 11.33 kPa = 5.000 m in altitude) were induced to Sprague-Dawley rats in the postnatal period as well as up to the 64th day of age, and after different recovery phases the ultrastructure of hepatocytes was qualitatively and quantitatively analysed. Major results were as follows: 1. Increases in body and liver weights were delayed but were balanced off after 64 days. 2. Qualitative alterations are reversible spherical transformations of mitochondria, a degradation of lipids and a slight increase in autophagocytosis. 3. The quantitative mitochondrial parameters (volume density, number per unit area, average volume) were not even adjusted to control values after 64 days. Granular endoplasmic reticulum and ribosomes/polysomes were insignificantly reduced in comparison to control animals, structure and arrangement are regular. Lipids and glycogen were differently altered. 4. The findings of the hepatocytes after postnatal hypoxia were reversible, though the majority of parameters had not yet returned to normal after 2 months. An adaptation to repetitive hypoxic conditions is not provable.

Topics: Animals; Animals, Newborn; Body Weight; Endoplasmic Reticulum; Glycogen; Hypoxia; Lipid Metabolism; Liver; Microscopy, Electron; Mitochondria, Liver; Rats; Rats, Inbred Strains

In experiments on rats with different resistance to oxygen deficiency (high-resistant--HR, and low-resistant LR animals) the myocardium ultrastructure of nonadapted and adapted rats was studied. It was shown that there were more glycogen granules and lipid drops initially in cardiomyocytes of nonadapted HR animals in comparison with LR ones. After a long-term adaptation to hypoxia the hypertrophia and hyperplasia of mitochondria, the nucleus and endoplasmatic reticulum hypertrophy were observed. Moreover, the increase of glycogen and lipids content was more pronounced in the myocardium of LR rats. Besides, the activation of protein-synthesizing processes was observed not only as a result of long-term adaptation, but also after single acute hypoxic effect. The results of submicroscopic cardiomyocyte studies of HR and LR rats are in good correlation with the peculiarities of energetic metabolism.

Topics: Acute Disease; Adaptation, Physiological; Animals; Cell Nucleus; Endoplasmic Reticulum; Glycogen; Hypertrophy; Hypoxia; Lipid Metabolism; Male; Mitochondria, Heart; Myocardium; Rats; Time Factors

With radiotracer and 13C nuclear magnetic resonance (13C-NMR) methods, we studied the time course of glycogen resynthesis after three 90-s episodes of hypoxemia in both control and diabetic rats in vivo. Glycogen synthesis was measured in the presence and absence of infused insulin and compared with the changes in glycogen synthase (GS) and phosphorylase activities. We observed in 13C-NMR spectra the expected mobilization of glycogen during hypoxia in vivo. In control rats with or without exogenous insulin, this was followed by a rapid resynthesis of glycogen during a 40-min recovery period. A marked activation of GS was observed by 10 min (glucose-6-phosphate-independent form of GS [GSl] = 0.65 mumol.min-1.g-1 or 92% of total GS), and activation persisted up to 40 min in both groups. Glycogen synthesis during the recovery period averaged 0.51 and 0.45 mumol.min-1.g-1 in the saline- and insulin-treated rats, respectively. In the diabetic rats by 10 min after hypoxemia, GSl increased only modestly in both saline-treated (0.16 mumol.min-1.g-1) and insulin-treated (0.21 mumol.min-1.g-1) rats, and activation persisted up to 40 min only with insulin treatment. Glycogen synthesis was slower in the diabetic rats given insulin (0.28 mumol.min-1.g-1) and essentially absent in the saline-treated rats (0.03 mumol.min-1.g-1) compared with controls. We conclude that recovery from hypoxemia is accompanied by a marked activation of GSl and rapid rates of glycogen synthesis in nondiabetic rats, and diabetes markedly blunts this response. Acute insulin infusion only partially overcomes this block.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Carbon Isotopes; Diabetes Mellitus, Experimental; Glucose; Glycogen; Glycogen Synthase; Heart; Hypoxia; Insulin; Magnetic Resonance Spectroscopy; Male; Myocardium; Phosphorylases; Rats; Rats, Inbred Strains; Reference Values

Isolated Langendorff-perfused rat hearts after 10 min pre-perfusion, were subjected to a substrate-free anoxic perfusion (20 min) followed by 20 min reperfusion with a glucose-containing oxygen-balanced medium. A similar experimental protocol was repeated in the presence either of 5 mM fructose or of 5 mM fructose-1,6-bisphosphate throughout the different perfusion conditions. High-energy phosphate compounds (adenosine triphosphate, creatine phosphate), adenine nucleotides, nicotinic coenzymes, lactate, pyruvate and glycogen content in the tissue were determined at the end of each perfusion period, while coronary flow, heart rate and lactate and pyruvate output were monitored throughout the whole duration of the experiments. On the whole, the results indicate that exogenous fructose-1,6-bisphosphate preserves high-energy metabolites during anoxia and restores myocardial metabolism and contractility during reperfusion, that a prolonged period of substrate-free anoxic perfusion renders the heart unable to normalize its metabolism during re-oxygenation and that fructose is not utilized by the heart for its energy demand. A possible hypothesis concerning the mechanism of action of fructose-1,6-bisphosphate is presented.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Chromatography, High Pressure Liquid; Fructosediphosphates; Glycogen; Hypoxia; Lactates; Male; Myocardial Reperfusion Injury; Myocardium; Phosphocreatine; Pyruvates; Rats; Rats, Inbred Strains

Hypoxia caused a progressive cytochalasin B-inhibitable increase in the rate of 3-O-methylglucose transport in rat epitrochlearis muscles to a level approximately six-fold above basal. Muscle ATP concentration was well maintained during hypoxia, and increased glucose transport activity was still present after 15 min of reoxygenation despite repletion of phosphocreatine. However, the increase in glucose transport activity completely reversed during a 180-min-long recovery in oxygenated medium. In perfused rat hindlimb muscles, hypoxia caused an increase in glucose transporters in the plasma membrane, suggesting that glucose transporter translocation plays a role in the stimulation of glucose transport by hypoxia. The maximal effects of hypoxia and insulin on glucose transport activity were additive, whereas the effects of exercise and hypoxia were not, providing evidence suggesting that hypoxia and exercise stimulate glucose transport by the same mechanism. Caffeine, at a concentration too low to cause muscle contraction or an increase in glucose transport by itself, markedly potentiated the effect of a submaximal hypoxic stimulus on sugar transport. Dantrolene significantly inhibited the hypoxia-induced increase in 3-O-methylglucose transport. These effects of caffeine and dantrolene suggest that Ca2+ plays a role in the stimulation of glucose transport by hypoxia.

Topics: 3-O-Methylglucose; Adenosine Triphosphate; Animals; Biological Transport, Active; Caffeine; Glucose; Glycogen; Hypoxia; In Vitro Techniques; Insulin; Male; Methylglucosides; Monosaccharide Transport Proteins; Muscles; Phosphocreatine; Rats; Rats, Inbred Strains

We compared extracellular and intracellular acid-base state in turtles (Chrysemys picta bellii) subjected to anoxic submergence to turtles made anoxic by N2-breathing. Measurements made on control animals and on animals after 1, 2, 4, or 6 h of anoxia included blood pH, PO2, PCO2, and lactate as well as liver, heart, skeletal muscle, and brain pHi (using DMO equilibration), lactate, and glycogen concentrations. We hypothesized that the anaerobic metabolic rate of submerged turtles would be depressed by the more severe extra- and intracellular acidosis, and that this would be indicated by reduced lactate accumulation and glycogen depletion. Submerged turtles became extremely acidemic due to a combined metabolic and respiratory acidosis and had significantly lower arterial pH than N2-breathing animals (6.98 and 7.34, respectively, after 6 h). In spite of this disparity in pHa, 6 h pHi values for liver, heart, and brain were similar. Likewise, our data on glycogen depletion and lactate accumulation at h 6 in these tissues suggest no dramatic differences in anaerobic metabolic rate. While skeletal muscle pHi was somewhat lower at h 6 in the submerged group (6.73 vs 6.91 for N2-breathers), we observed no differences in either glycogen depletion or lactate accumulation in this tissue between our two treatments. Thus, at h 6, in spite of a 0.37 pH unit difference in pHa and a nearly 70 mm Hg difference in arterial and presumably cytosolic PCO2, pHi and tissue lactate and glycogen concentrations were similar. These results can be explained if the in vivo intracellular buffer values (beta) of turtle tissues are very high. We conclude that extracellular acid-base state is not necessarily reflected intracellularly in vivo in turtles and care must be taken in extrapolating from one compartment to another when attempting to make inferences about metabolic depression or acid-base regulation in this species.

Topics: Acid-Base Equilibrium; Animals; Brain; Female; Glycogen; Hypoxia; Liver; Male; Myocardium; Nitrogen; Respiration; Turtles

The purpose of this study was to compare the degree of ischemic and hypoxic injury in normal versus hypertrophied rat hearts to investigate basic mechanisms responsible for irreversible myocardial ischemic injury. Hearts from rats with bands placed on the aortic arch at 23 days of age (BAND) and sham-operated rats (SHAM, 8 weeks postoperative) were isolated, perfused with Krebs buffer, and had a left ventricular balloon to measure developed pressure. Hearts were made globally ischemic until they developed peak ischemic contracture and were reperfused for 30 minutes. Additional hearts were perfused for 15 minutes with glucose-free hypoxic buffer followed by 20 minutes of oxygenated perfusion. There was an 87% increase in heart weight of BAND compared with SHAM (p less than 0.01). During ischemia, lactate levels increased faster in BAND compared with SHAM, ischemic contracture occurred earlier in BAND than in SHAM despite no difference in ATP levels, and postischemic recovery of left ventricular pressure was less in BAND (26.8 +/- 5.6% of control left ventricular pressure, mean +/- SEM) compared with SHAM (40 +/- 4.6%, p less than 0.05). During hypoxic perfusion, lactate release was greater in BAND than in SHAM (48.8 +/- 1.2 versus 26.6 +/- 0.97 mumols/g, p less than 0.01), and with reoxygenation, lactate dehydrogenase release was less in BAND than in SHAM (13.2 +/- 0.7 versus 19.5 +/- 0.2 IU/g, p less than 0.01). After hypoxia and reoxygenation, left ventricular pressure recovery was greater in BAND than in SHAM (93 +/- 8.4% versus 66 +/- 5.3%, p less than 0.01). Thus, this study suggests that hypertrophied hearts have a greater potential for glycolytic metabolism, resulting in an increased rate of by-product accumulation during ischemia, which may be responsible for the increased susceptibility of hypertrophied hearts to ischemic injury.

Topics: Adenosine Triphosphate; Animals; Aorta; Cardiomegaly; Constriction; Coronary Disease; Glycogen; Heart Ventricles; Hypoxia; Lactates; Lactic Acid; Male; Microscopy, Electron; Myocardial Contraction; Myocardium; Phosphocreatine; Pressure; Rats; Rats, Inbred Strains

The importance of the glucose/fatty acid cycle in the control of cardiac lipolysis is emphasized by the following observations. Addition of the glycogen debranching inhibitor deoxynojirimycin or an O2-vehicle, fluorocarbon F-43, to media perfusing paced, lipid-enriched, Langendorff hearts lower cardiac lactate and glycerol 3-phosphate levels together with inhibition of glucagon-stimulated glycerol (and lactate) release. The absence of fluorocarbon during perfusion of 5 Hz paced langendorff hearts probably results in limited tissue oxygenation, resulting in glycogenolysis and lipolysis. The results indicate hormonal control of cardiac lipolysis by glyco(geno)lysis.

Topics: 1-Deoxynojirimycin; Animals; Glucagon; Glucosamine; Glycerol; Glycogen; Glycolysis; Hypoxia; In Vitro Techniques; Lactates; Lipolysis; Myocardium; Rats

The effects of elevated glucose on cardiac function during hypoxia were investigated in isolated arterially perfused rabbit interventricular septa. Rest tension, developed tension, intracellular potential, 42K+ efflux, lactate production, exogenous glucose utilization, and tissue high-energy phosphate levels were measured during a 50-min period of hypoxia with 4, 5, or 50 mM glucose present (isosmotically balanced with sucrose) and during reoxygenation for 60 min with perfusate containing 5 mM glucose/45 mM sucrose. At physiologic (4 or 5 mM) and supraphysiologic glucose (50 mM), lactate production and high-energy phosphate levels during hypoxia were equally well maintained, yet cardiac dysfunction was markedly attenuated by 50 mM glucose. Despite identical rates of total glycolytic flux, exogenous glucose utilization was enhanced by 50 mM glucose so that tissue glycogen levels remained normal during hypoxia, whereas glycogen became depleted with 4 or 5 mM glucose present during hypoxia. Most of the beneficial effects of 50 mM glucose occurred during the first 25 min of hypoxia. Prior glycogen depletion had no deleterious effects during hypoxia with 50 mM glucose present, but exacerbated cardiac dysfunction during hypoxia with 5 mM glucose present. These findings indicate that enhanced utilization of exogenous glucose improved cardiac function during hypoxia without increasing total glycolytic flux or tissue high-energy phosphate levels, suggesting a novel cardioprotective mechanism.

Topics: Animals; Coronary Disease; Cyclic AMP; Energy Metabolism; Glucose; Glycogen; Glycolysis; Heart; Hypoxia; Insulin; Potassium; Rabbits

13C-NMR natural-abundance spectra of specimens of Arenicola marina obtained, showed seasonal changes in the concentration of some metabolites, with the osmolite alanine as well as triacylglyceride storage compounds present at high concentrations. Glycogen was sometimes only barely detectable due to the low natural abundance level of 13C. Glycogenic metabolism of the lugworm A. marina was studied in vivo by 13C-NMR spectroscopy using 13C-labelled glucose. During recovery from a hypoxic period [1-13C]glucose was incorporated into glycogen. [1-13C]Glucose was injected 5 h after the end of hypoxia to guarantee sufficient and reliable 13C labelling of glycogen. An earlier injection of [1-13C]glucose led to considerably diminished incorporation of 13C-labelled glucosyl units into glycogen, probably due to the consumption of the available glucose as fuel for ATP production. No scrambling of 13C into the C6 position of glycogen was observed, indicating a lack of gluconeogenic activity. 13C was also incorporated into the C3 positions of alanine and alanopine. To assign correctly this last 13C-NMR resonance, the compound was synthesized biochemically. No labelling of glycogen was observed when [3-13C]alanine was injected into the coelomic cavity with similar incubation conditions being used. The 13C of [1-13C]glucose, incorporated into glycogen, showed a very low turnover rate in normoxic lugworms as shown by two 13C(1H)-NMR spectra, one obtained 48 h after the other. On the other hand, in hypoxia lugworms the signal due to 13C-labelled glycogen decreased very rapidly proving a high turnover rate. The disappearance of 13C from glycogen during the first 24 h of hypoxia indicates that the last glycosyl units to be synthesized are the first to be utilized. Lugworms were quite sensitive to the 1H-decoupling field used for obtaining the 13C(1H)-NMR spectra, especially at 11.7 T. Using bi-level composite-pulse decoupling and long relaxation delays, no tissue damage or stress-dependent phosphagen mobilization, as judged by 31P-NMR spectroscopy, was observed.

Topics: Alanine; Animals; Carbon; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Magnetic Resonance Spectroscopy; Polychaeta; Succinates; Succinic Acid

Thoroughbred horses were exercised to fatigue on a treadmill at 62% and 100% of their VO2max. Hypoxemia occurred at the onset of exercise under both exercise conditions. This hypoxemia persisted to fatigue during the heavy exercise but progressively diminished as the exercise continued and had disappeared by the end of exercise at the lighter load. As a result of the hypoxemia the oxygen content of arterial blood during exercise at VO2max was 17% below its carrying capacity. However, under both experimental conditions the CaO2 still exceeded that of rest owing to an elevation in hemoglobin concentration. The temperature of blood at the point of fatigue was similar, 41.0 +/- 0.2 degrees C and 41.1 +/- 0.2 degrees C, for exercise at 62% and 100% VO2max, respectively. Muscle samples collected at rest and at the termination of exercise did not demonstrate major differences between the exercise conditions except for a higher [lactate] and lower pH following the heavy exercise. From these results it can be suggested that the combined effects of an elevated body temperature, changes in muscle pH, and oxygen delivery may all be factors contributing to limit exercise capacity in the horse.

Topics: Adenosine Triphosphate; Animals; Blood Gas Analysis; Body Temperature; Glycogen; Horses; Hydrogen-Ion Concentration; Hypoxia; Lactates; Muscles; Oxygen; Oxygen Consumption; Phosphocreatine; Physical Conditioning, Animal; Pulmonary Gas Exchange; Respiration

The effect of delay in obliteration of the umbilical cord on the time-courses of liver glycogen, blood glucose and lactate concentrations and blood PO2, PCO2 and pH during the first 6 h of extrauterine life were studied. Obliteration of the umbilical cord 2 h after delivery resulted in an increase in liver glycogenolysis without significantly affecting the other parameters studied. A 6-hour delay in obliteration of the umbilical cord increased lactiacidemia and decreased blood PO2 and pH without significantly affecting the other parameters studied. A supply of pure oxygen to the newborns decreased lactiacidemia and increased PO2, although the differences between obliterated and nonobliterated newborns remained. These results suggest that hypoxia due to the persistence of placental circulation results in an increase in lactiacidemia as a consequence of a decrease in lactate utilization.

Topics: Animals; Animals, Newborn; Blood Gas Analysis; Blood Glucose; Glycogen; Hypoxia; Lactates; Liver; Rats; Rats, Inbred Strains; Umbilical Cord

Myocardial hypoxia, induced by arrest of the artificial ventilation of anaesthetized open-chest rats, was utilized in order to study some aspects of the regulation of myocardial glycogen metabolism. Atenolol, a cardioselective beta-adrenergic receptor antagonist, and verapamil, an inhibitor of sarcolemmal calcium transfer, were used to determine the respective role of adenosine 3', 5'-cyclic monophosphate (cAMP) and calcium in the activation of the enzymes of glycogen phosphorolysis and synthesis. Glycogen degradation is reduced by atenolol treatment, as a consequence of a reduced activation of glycogen phosphorylase. Verapamil treatment has no significant effect, neither on the enzyme activation nor on the glycogen utilization. The activation of glycogen synthase, expressed by the conversion of the enzyme from the D to the I form, which results from the decrease in glycogen stores during hypoxia, is lowered under the effect of both drugs. However, in the beta-blocker treatment case, this effect results from a lower glycogen depletion while this effect is more specific in hearts from rats treated with verapamil. Under the effect of verapamil, the reduction of synthase activation, for a similar depletion of glycogen stores, was confirmed by experiments using isolated rat hearts submitted to ischaemia. These results show that: 1. the glycogenolysis in the hypoxic myocardium in situ is mainly controlled by a cAMP-dependent enzyme conversion or by metabolic allosteric effectors; 2. the activation of myocardial glycogen synthase, which is essentially correlated to the reduction of glycogen stores, is also calcium-dependent and most probably totally cAMP-independent.

Topics: Animals; Atenolol; Calcium; Cyclic AMP; Enzyme Activation; Female; Glycogen; Glycogen Synthase; Heart; Hypoxia; Myocardium; Phosphorylases; Rats; Rats, Inbred Strains; Verapamil

Concentrations of glycolytic intermediates and adenine nucleotides have been estimated in adductor muscle and hepatopancreas from the sea mussel Mytilus galloprovincialis Lmk. after various periods of valve closure. Mass action ratios of enzyme steps involved in the metabolism of these components are compared with their equilibrium constants. This reveals hexokinase, phosphofructokinase, pyruvate kinase and fructose-1,6-bisphosphatase catalyze non-equilibrium reactions. The changes in the concentrations of the glycolytic intermediates and in the rate M.A.R./Keq during hypoxia suggest that the carbon flow after valve closure is first controlled by phophofructokinase, but later on the rate of transformation of phosphoenolyruvate regulates this flow.

Topics: Animals; Bivalvia; Digestive System; Glycogen; Glycolysis; Hypoxia; Muscles; Phosphofructokinase-1; Pyruvate Kinase

This study tests the hypothesis that catecholamines regulate glucose availability during hypoxia in the rainbow trout by activating glycogen phosphorylase (GPase) while inhibiting pyruvate kinase (PK) in the liver. The net result would be an increase in liver glycogenolysis and a reduction of glycolysis and/or enhancement of gluconeogenesis. We used the criteria of Stalmans & Hers (1975) and report much lower resting percent GPase a (active) values (20-30%) than those previously published. Dorsal aortic injections of epinephrine or norepinephrine increased plasma glucose (16-46%), had no effect on liver or muscle glycogen levels, decreased the activity of PK, and increased total and percent GPase a activities. Pre-treatment with the beta-adrenoreceptor antagonist propranolol eliminated these effects. During moderate hypoxia, plasma glucose remained unchanged, while lactate levels increased fourfold. When fish were pre-treated with propranolol, hypoxia depressed plasma glucose levels (-26%), total and percent GPase a, and increased PK activity, suggesting that hypoxia mediated the dephosphorylation of these enzymes. We conclude that catecholamines stimulate hepatic beta-adrenoreceptors during hypoxia and sustain plasma glucose levels by nullifying the deleterious effects of hypoxia on metabolic function. The specific metabolic consequences of these catecholamine-mediated effects are an increase in the activity of the active form of GPase and a reduction in PK activity, which suggests an activation of glycogenolysis and an inhibition of glycolysis and/or activation of gluconeogenesis, respectively.

Topics: Animals; Catecholamines; Epinephrine; Female; Gluconeogenesis; Glycogen; Hypoxia; Kinetics; Liver; Male; Muscles; Norepinephrine; Phosphorylases; Pyruvate Kinase; Salmonidae; Trout

Topics: Animals; Bivalvia; Glycogen; Glycolysis; Hypoxia

The cerebral concentrations of phosphatidylinositol (PI), phosphatidylinositol 4-phosphate (PIP), phosphatidylinositol 4,5-bisphosphate (PIP2), phosphatidic acid (PA), triacylglycerol (TAG) and free fatty acids (FFA), as well as cerebral metabolites, were measured in rats subjected to 10 min of hypoxia and subsequent recovery of 7 or 30 min duration. The experiments were carried out with control of physiological variables. Hypoxia (paO2 values of about 15 mm Hg) caused a decrease in PI, whereas PIP and PIP2 did not change significantly. A two-fold increase of total FFA was noted, mainly comprising stearic and arachidonic acids. TAG-arachidonate tended to increase, but the other species in TAG decreased. Adenosine triphosphate (ATP) and energy charge (EC) decreased slightly and there was a marked lactate accumulation. PA did not change throughout the experiment. With recovery of 7 min duration, PI decreased further and total FFA continued to increase. TAG-arachidonate increased significantly. ATP remained depressed but EC recovered to the control range. Both tissue and plasma glucose increased. Tissue lactate remained elevated and systemic acidosis occurred. After a recovery period of 30 min, all lipids normalized and the energy state returned toward control. The data suggest that the phosphoinositide alterations during hypoxia are metabolically linked to changes in FFA and the lipid changes are accompanied by alterations in cerebral energy and carbohydrate metabolism. The selective increase in TAG-arachidonate may represent an incorporation of arachidonic acid into TAG, which may serve to reduce the free arachidonic acid level in the brain.

Topics: Animals; Brain; Energy Metabolism; Fatty Acids; Glycogen; Hypoxia; Lipid Metabolism; Male; Phosphatidylinositols; Phosphocreatine; Pyruvates; Pyruvic Acid; Rats; Rats, Inbred Strains; Triglycerides

The relationships between the concentrations of glycogen, glucose, lactate, adenosine triphosphate (ATP) and hypoxanthine in the brain tissue, and the hypoxanthine and lactate concentration in cerebrospinal fluid and blood were examined after exposure of rats to hypoxia. The animals (1 and 10 days old) were exposed to hypobaric hypoxia for 1-12 h, pO2 11.3 kPa (mild), pO2 8.6 kPa (moderate), pO2 6.4 (strong) and pO2 4.7 kPa (severe) in inspired air. The concentration of hypoxanthine in both cerebrospinal fluid and brain tissue increases in severe hypoxia. This severe hypoxia was related to a decrease of ATP level in brain tissue. This study showed that the level of hypoxanthine in blood did not closely correlate to the level of hypoxanthine in brain tissue and cerebrospinal fluid. Extremely high hypoxanthine values in the blood might indicate a decrease in ATP content in brain tissue.

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Blood Glucose; Brain; Glycogen; Hypoxanthine; Hypoxanthines; Hypoxia; Lactates; Lactic Acid; Rats; Rats, Inbred Strains

Isolated cardiac tissue from the ferret was repeatedly exposed to anoxia while perfused with glucose-containing Tyrode solution. In one series of experiments, papillary muscles were injected with aequorin to measure intracellular Ca2+. On the first exposure to anoxia, the Ca2+ transients often increased, but on subsequent exposures this increase disappeared and eventually the Ca2+ transients declined on exposure to anoxia. This decline in the Ca2+ transients could be converted back to an increase by a 1 h exposure to an elevated (x5) glucose concentration. Exposure of aerobic muscles to 10 mM lactic acid caused a similar increase in the Ca2+ transients to that seen in early exposures to anoxia. In a second series of experiments, performed on Langendorff-perfused hearts, measurements were made of glycogen concentration preceding, and lactate production during, exposures to anoxia. At a constant level of glucose, glycogen concentration and lactate production were found to decline on repeated exposures to anoxia, and both were increased after a period of elevated glucose and reduced stimulation frequency. These results suggest that the response of the Ca2+ transients to anoxia is dependent on the metabolic status of the muscle. The increase in the Ca2+ transients during an early exposure to anoxia may be a consequence of lactic acid production due to accelerated glycolysis. Repeated exposures to anoxia reduce glycogen concentration and lactate production and this reduces the rise in the Ca2+ transients.

Topics: Animals; Calcium; Ferrets; Glycogen; Hypoxia; In Vitro Techniques; Lactates; Myocardium; Papillary Muscles

The contributions of five variables believed to influence the brain's metabolism of O2 during hypoxia [duration, PaO2, delta CMRO2 (the difference between normal and experimental oxygen uptake), O2 availability (blood O2 content.CBF), and O2 deficit (delta CMRO2.duration)] were assessed by stepwise and multiple linear regression. Levels of brain tissue carbohydrates (lactate, glucose, and glycogen) and energy metabolites [ATP, AMP, and creatine phosphate (CrP)] were significantly influenced by O2 deficit during hypoxia, as was final CMRO2. After 60 min of reoxygenation, levels of tissue lactate, glucose, ATP, and AMP were related statistically to the O2 deficit during hypoxia; however, CMRO2 changes were always associated more significantly with O2 availability during hypoxia. Creatine (Cr) and CrP levels in the brain following reoxygenation were correlated more to delta CMRO2 during hypoxia. Changes in some brain carbohydrate (lactate and glucose), energy metabolite (ATP and AMP) levels, and [H+]i induced by complete ischemia were also influenced by O2 deficit. After 60 min of postischemic reoxygenation, brain carbohydrate (lactate, glucose, and glycogen) and energy metabolite (ATP, AMP, CrP, and Cr) correlated with O2 deficit during ischemia. We conclude that "O2 deficit" is an excellent gauge of insult intensity which is related to observed changes in nearly two-thirds of the brain metabolites we studied during and following hypoxia and ischemia.

Topics: Adenine Nucleotides; Animals; Brain; Cerebrovascular Circulation; Creatine; Dogs; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Ischemic Attack, Transient; Lactates; Lactic Acid; Oxygen; Oxygen Consumption; Phosphocreatine; Regression Analysis

Experiments were performed to check the tolerance to severe hypoxia of the tissue layers (compact and spongy) of the tortoise heart. The animals were subjected to hypoxia (7% O2) at 18 degrees C, 28 degrees C and 38 degrees C for 30, 6 and 2 hr respectively, or to anoxia for 30 hr at 18 degrees C and 2 hr at 38 degrees C. At 18 degrees C the metabolic alterations caused by a 30 hr hypoxia were mild whereas at 28 degrees C and 38 degrees C the cardiac glycogen was depleted, lactate had accumulated and the phosphate creatine and ATP content had decreased. The extent of these metabolic changes was similar in the compact and in the spongy layers of the heart.

Topics: Adenosine Triphosphate; Animals; Glycogen; Heart; Hypoxia; Kinetics; Lactates; Myocardium; Phosphocreatine; Turtles

To compare the function of old and young hearts contracting under identical conditions, isolated hearts of young and old C57BL/6J mice were perfused using a Langendorff preparation. During a 3-min period of anoxia some hearts showed a decrease in systolic pressure, while other hearts developed contracture. The incidence and magnitude of contracture was greater in the old hearts and they also showed a significantly larger decline in contractility. Increasing the glucose concentration improved the performance of both age groups but the performance of the old hearts was still inferior to that of the young. The glycogen content and utilization were virtually the same in the two age groups. When iodoacetate was added, all hearts developed contracture and the magnitude of the contracture was greater than in the absence of iodoacetate; during the period of reoxygenation, the young hearts recovered but, the old hearts developed a second contracture. A brief period of anoxia is more debilitating to old C57BL/6J hearts than to young ones.

Topics: Aging; Animals; Glucose; Glycogen; Heart; Hypoxia; In Vitro Techniques; Iodoacetates; Iodoacetic Acid; Male; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocardium; Perfusion; Pressure

An in vivo brain perfusion technique was used to examine effects of hypoxia on cerebral cortical metabolism in barbiturate-anesthetized rats. Dulbecco's phosphate-buffered solution (PBS), or Dulbecco's PBS + 6 mM glucose, was infused into the right carotid circulation for 0 to 3 min, at a rate that reduced regional cerebral blood flow to the ipsilateral parietal lobe by more than 40% and O2 delivery by about 50%. The duration of infusion of either solution was correlated negatively with the ipsilateral parietal lobe concentrations of glucose, ATP, and phosphocreatine (PCr), and positively with parietal concentrations of lactate and cAMP. cGMP increased in relation to infusion duration of Dulbecco's PBS. Statistically significant elevations of brain lactate occurred after 1 min of infusion of Dulbecco's PBS; lactate was elevated and glucose was reduced after 2 min of infusion of either solution. Brain ATP, PCr, and glycogen concentrations decreased in relation to the elevation in brain lactate, and the [PCr]:[ATP] ratio declined. The results demonstrated that limited hypoxia stimulated cerebral glycolysis and produced a concurrent decrease in brain ATP and PCr. However, ATP was spared to a degree, at the expense of PCr.

Topics: Adenosine Triphosphate; Animals; Brain; Carotid Arteries; Cerebrovascular Circulation; Cyclic AMP; Cyclic GMP; Glucose; Glycogen; Hypoxia; Lactates; Male; Oxygen; Parietal Lobe; Perfusion; Phosphocreatine; Rats; Rats, Inbred Strains

The effect of three calcium antagonists on the synthesis of prostacyclin (PGI2, assayed as 6-Keto-PGF1 alpha) and PGE2 by cultured rat cardiac myocytes and fibroblasts was investigated. In myocytes only, bepridil, diltiazem and verapamil (10(-9) to 10(-7) M) stimulated PGs synthesis by two- to three-fold, dose-dependently. At a concentration of 10(-6) or 10(-5) M the intensity of the stimulation of PGI2 and PGE2 decreased. Cobalt chloride (2 X 10(-3) M) did not change PGs synthesis (pg/mg of protein/30 min; means +/- SE, N = 10; PGE2: 365 +/- 59 and 463 +/- 89 treated vs controls; PGI2: 824 +/- 214 and 799 +/- 143 treated vs controls). After 30 min exposure of myocytes to hypoxic conditions (glucose-free medium and low PO2), the glycogen content was half that of the controls (P less than 0.001), ATP content did not change and PGI2 and PGE2 synthesis increased (X1.5, P less than 0.05). When applied to myocytes 30 min before inducing hypoxia, the three calcium antagonists stimulated PGs synthesis by three- to seven-fold at maximal effect, and bepridil (10(-8) M) or diltiazem (10(-7) M) prevented the hypoxia-induced decrease in glycogen content. With 10(-5) M drug concentration, the effect on PGs was not significant, except for the effect of bepridil on PGI2 (P less than 0.05). It is concluded that therapeutic concentrations of calcium antagonists simultaneously prevent the decrease in myocyte glycogen induced by hypoxia and stimulate PGs synthesis by myocytes.

Topics: Animals; Bepridil; Calcium Channel Blockers; Cells, Cultured; Cobalt; Diltiazem; Dinoprostone; Epoprostenol; Fibroblasts; Glycogen; Heart; Hypoxia; Myocardium; Prostaglandins E; Pyrrolidines; Rats; Rats, Inbred Strains; Verapamil

We determined changes in rat plantaris, diaphragm, and intercostal muscle metabolites following exercise of various intensities and durations, in normoxia and hypoxia (FIO2 = 0.12). Marked alveolar hyperventilation occurred during all exercise conditions, suggesting that respiratory muscle motor activity was high. [ATP] was maintained at rest levels in all muscles during all normoxic and hypoxic exercise bouts, but at the expense of creatine phosphate (CP) in plantaris muscle and diaphragm muscle following brief exercise at maximum O2 uptake (VO2max) in normoxia. In normoxic exercise plantaris [glycogen] fell as exercise exceeded 60% VO2max, and was reduced to less than 50% control during exhaustive endurance exercise (68% VO2max for 54 min and 84% for 38 min). Respiratory muscle [glycogen] was unchanged at VO2max as well as during either type of endurance exercise. Glucose 6-phosphate (G6P) rose consistently during heavy exercise in diaphragm but not in plantaris. With all types of exercise greater than 84% VO2max, lactate concentration ([LA]) in all three muscles rose to the same extent as arterial [LA], except at VO2max, where respiratory muscle [LA] rose to less than half that in arterial blood or plantaris. Exhaustive exercise in hypoxia caused marked hyperventilation and reduced arterial O2 content; glycogen fell in plantaris (20% of control) and in diaphragm (58%) and intercostals (44%). We conclude that respiratory muscle glycogen stores are spared during exhaustive exercise in the face of substantial glycogen utilization in plantaris, even under conditions of extreme hyperventilation and reduced O2 transport. This sparing effect is due primarily to G6P inhibition of glycogen phosphorylase in diaphragm muscle. The presence of elevated [LA] in the absence of glycogen utilization suggests that increased lactate uptake, rather than lactate production, occurred in the respiratory muscles during exhaustive exercise.

Topics: Animals; Diaphragm; Glycogen; Hypoxia; Intercostal Muscles; Lactates; Lactic Acid; Male; Muscle, Smooth; Oxygen Consumption; Phosphates; Physical Exertion; Rats; Rats, Inbred Strains; Respiratory System

An investigation was made into the effects of physical exercise upon heart glycogen change in rats exposed to decreased barometric pressure in hypobaric chamber simulating the effects of 3,000 m and 5,000 m altitude. Blood and cardiac tissue samples were examined after 1 h and 5 h of treadmill running at sea level and at 3,000 m, and after 1 h at 5,000 m. At sea level, cardiac glycogen level showed a classic biphasic evolution which was not affected by running. At 3,000 m, 1 h of running promoted an initial increase of 16% from control values, while a secondary decrease of 15% was measured after 5 h of running. Running for 1 h at 5,000 m induced a total depletion in cardiac glycogen level, the latter being depressed by 90% from control values. Free fatty acid (FFA) plasma level was increased by physical exercise at all barometric pressures, but the response was gradually enhanced by hypoxia. These data indicate that heart glycogen utilization during prolonged physical exercise is stimulated by acute altitude exposure, which suppresses the sparing effect observed at sea level upon dependence of enhanced FFA availability. The great differences in cardiac glycogen utilization support the views that enhanced glycogenolysis during hypoxia is promoted by different parameters, thus affecting various pathways. The slight decrease at 3,000 m suggests a moderate increase in anaerobic metabolism while the exhaustion observed after 1 h of running at 5,000 m indicates a decrease in cellular respiration response and enhanced heart anaerobic metabolism.

Topics: Animals; Atmospheric Pressure; Fatty Acids, Nonesterified; Glycogen; Hypoxia; Male; Myocardium; Physical Exertion; Rats; Rats, Inbred Strains

Twenty four male Sprague-Dawley rats, 35 days old, were randomly assigned to one of four groups: 2 resting control groups and 2 swimming groups. The sea level-control and the sea level-swimming groups were housed 5 weeks at 1,011 hPa (760 mmHg) while the hypoxic control and swimming groups were housed for 1 week at 678 hPa, followed by 4 weeks at 611 hPa. The swimming rats were subjected to a swimming program of 30 min, 6 days/week for 5 weeks. Both hypoxia groups developed significantly higher Hb and Hct levels than the sea level groups. The glycogen content in the extensor digitorum longus (EDL) and the deep portion of the vastus lateralis (DVL) muscles of the sea level-swimming group were significantly greater as compared to the hypoxia swimming group. The succinate dehydrogenase (SDH) activity in the sea level-control group was significantly lower in the EDL muscle than in the 3 other groups, and in the DVL muscle lower than that of the sea level-swimming group. Histochemically, hypoxia and swimming training induced significant increases in the fast-twitch-oxidative-glycolytic (FOG) fibers (6-11%) in soleus muscle, and decreases in the slow-twitch-oxidative (SO) fibers. The EDL muscles had significantly higher percentages of FOG fibers in the hypoxia and swimming groups than in the sea level-control group. On the basis of the present study it seems probable that hypoxia is a triggering factor for the conversions of muscle fiber types and the increase in oxidative capacity.

Topics: Acclimatization; Aging; Animals; Atmospheric Pressure; Blood Proteins; Body Weight; Glycogen; Hematocrit; Hemoglobins; Hypoxia; Male; Muscle Development; Muscles; Myocardium; Phosphofructokinase-1; Physical Exertion; Rats; Rats, Inbred Strains; Succinate Dehydrogenase; Swimming

We have compared the capacity of major organs to produce lactic acid from endogenous sources relative to their ability to buffer that proton load. We deduced that the ultimate source for the rapid production of a very large amount of lactic acid must be hepatic and/or muscle glycogen or exogenous glucose, because the quantity of endogenous glucose is quite small and the rate of net protein catabolism is too slow. Of the organs examined, only the liver of fed persons can produce sufficient lactic acid to markedly overwhelm its own buffer capacity plus that of the ECF and other tissues. Moreover, it is important to realize that a fasted (low hepatic glycogen) subject who lacks the stimulus for muscle glycogenolysis can only develop a modest degree of acute lactic acidosis owing to a limited precursor availability; under these circumstances, hypoglycemia and/or localized tissue necrosis could be the major threats to that patient. We present two examples with more chronic lactic acidosis without hypoxia emphasizing that tissue catabolism may be necessary to support high rates of lactic acid production, and we suggest that a high plasma lactate concentration need not be present to observe a large turnover of this metabolite.

Topics: Acid-Base Equilibrium; Acidosis; Adenosine Triphosphate; Animals; Bone and Bones; Extracellular Space; Glucose; Glycogen; Humans; Hydrogen-Ion Concentration; Hypoxia; Intracellular Fluid; Kidney; Lactates; Liver; Muscle Proteins; Muscles; NAD

The ultrastructural and ultrahistochemical properties of post-mortem changed and hypoxic heart tissue of Gadus virens, Gadus morhua, and Poecilia reticulata are described. When incubated for 0.5 h at 20 degrees C the cardiac tissue is rich in vacuoles and endocardial blebs. After 1 h of incubation, the myocardial mitochondria contain some amorphous, flocculent densities (50-100 nm), which seem to increase in number and size with advancing incubation time. Furthermore, the mitochondria in heart perfused by a calcium-containing solution for 7 h at hypoxic conditions contain large numbers of highly electron dense annular-granules (35-50 nm). Numerous myocardial mitochondria exclude tannic acid in tissue incubated or perfused for up to 1.5 h, whereas all mitochondria seem permeated by this substance when incubated for 5 h or perfused at hypoxic condition for 7 h. The amount of myocardial glycogen in P. reticulata is greatly reduced in the hypoxic heart compared with the normal heart. The mitochondria and contractile material, however, seem to tolerate oxygen depletion remarkably well. The present results are compared with those reported previously for the post-mortem changes and hypoxic hearts in fishes and mammals.

Topics: Animals; Fishes; Glycogen; Hypoxia; Microscopy, Electron; Microscopy, Electron, Scanning; Myocardium; Perfusion; Postmortem Changes

An ischaemia-like state in cultured heart cells has been obtained by markedly restricting the volume of extracellular medium combined with total deprivation of oxygen (anoxia) and glucose. Cellular injury, as reflected by the release of both cytoplasmic and lysosomal enzymes was significantly greater than during anoxia alone (oxygen deprivation with a larger extracellular volume). This is most likely due to inadequate washout of metabolites during "ischaemia" rather than reduced energy production since glycolytic flux as reflected by lactate production was similar in both experimental states. Glucose administration during either anoxia or "ischaemia" delayed enzyme release. We believe that cytoplasmic enzymes are released mainly during the reversible period of oxygen deprivation, while lysosomal enzyme release reflects the onset or irreversible injury, occurring at a time when ATP levels and glycogen stores are almost completely exhausted.

Topics: Animals; Cells, Cultured; Coronary Disease; Culture Media; Glucose; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lysosomes; Myocardium; Time Factors

The effects of carbon monoxide (CO) or nitrogen (N2) anoxia were assessed and compared in stimulated (360 beats/min) and unstimulated isolated rat hearts. The hearts were perfused through the aorta with Krebs-Henseleit solution aerated with 95% O2-5% CO2 (O2). Heart rate, pulse pressure, perfusate flow, and perfusate lactate concentrations were recorded. After 30 min of O2 perfusion, the hearts were challenged with 95% CO-5% CO2 (CO) or 95% N2-5% CO2 (N2) for 10 min. The preparations were then reoxygenated and allowed to recover for 10 min. In the unstimulated hearts, CO depressed heart rate, pulse pressure, and perfusate flow earlier than did N2. Lactate concentrations increased to a greater extent with N2 than with CO. With reoxygenation heart rate, pulse pressure, and lactate concentrations returned to control values earlier in the CO hearts. The differences observed in pulse pressure and lactate concentrations with CO and N2 anoxia disappeared with stimulation. There were no significant differences in water or glycogen contents after CO or N2 in either the unstimulated or stimulated preparations. These results suggest that CO may have a direct effect on the myocardium in addition to its well-known anoxic effect.

Topics: Animals; Carbon Monoxide; Electric Stimulation; Glycogen; Heart; Heart Rate; Hypoxia; Lactates; Lactic Acid; Male; Myocardium; Nitrogen; Rats; Rats, Inbred Strains

Isolated guinea pig hearts were used to determine whether an extracellular (interstitial) or intracellular pool of myocardial adenosine is most important in attenuating the catecholamine-induced enhancement of cardiac contractile state and glycogenolysis. Isoproterenol (2 X 10(-8) M) stimulation of hypoxic (30% O2) perfused hearts produced a marked elevation in tissue and effluent perfusate adenosine levels that were greater than the increases observed with the isoproterenol stimulation of oxygenated hearts (95% O2). In the isoproterenol stimulated hypoxic hearts nitrobenzylthioinosine (NBMPR), a potent inhibitor of adenosine cellular transport, further increased tissue adenosine content and markedly decreased the perfusate level of the nucleoside. Assuming that perfusate levels of adenosine correlate directly with extracellular levels, NBMPR was used as a tool to increase the intracellular and decrease the extracellular content of the nucleoside. When compared to responses in oxygenated hearts, hypoxia reduced the isoproterenol-produced increase in myocardial cyclic AMP content, cyclic AMP-dependent protein kinase activity and contractility but enhanced the increase in glycogen phosphorylase alpha formation. NBMPR completely prevented the reduction of the isoproterenol-induced cyclic AMP and cyclic AMP-dependent protein kinase responses but only partially prevented the attenuation of the contractile response. The increase in phosphorylase alpha formation in the hypoxic isoproterenol stimulated hearts was not influenced by NBMPR. The results suggest that an increase in extracellular adenosine is more influential than an elevation of intracellular adenosine in attenuating beta-adrenoceptor-elicited increases in myocardial cyclic AMP content, cyclic AMP-dependent protein kinase activity and contractile state.

Topics: Adenosine; Animals; Catecholamines; Cyclic AMP; Extracellular Space; Female; Glycogen; Guinea Pigs; Heart; Hypoxia; Intracellular Fluid; Isoproterenol; Myocardial Contraction; Myocardium; Thioinosine

Intermittent high altitude hypoxia (8 hours a day, 5 days a week, stepwise up to the altitude of 7000 m, total number of exposures 24) induced in male and female rats, chronic pulmonary hypertension and right ventricular hypertrophy. No significant sex differences were found in both these parameters. A significant sex difference was demonstrated in the resistance of the cardiac muscle to acute anoxia in vitro: the myocardium of control female rats proved to be significantly more resistant to oxygen deficiency. Intermittent altitude hypoxia resulted in significantly enhanced resistance in both sexes, yet the sex difference was maintained. Sex differences were further observed in the growth response of experimental animals to the acclimatization process. Whereas the body weight of male rats exposed to intermittent altitude hypoxia was significantly lower, hypoxic females had body weights comparable to those of control animals.

Topics: Altitude; Animals; Body Weight; Cardiomegaly; Female; Glycogen; Hemodynamics; Hemoglobins; Hypertension, Pulmonary; Hypoxia; Male; Myocardial Contraction; Myocardium; Rats; Rats, Inbred Strains; Sex Factors

Riboxine stimulates activation of redox biosynthetic processes and raises aerobic production of energy in rat myocardium. Under pressure chamber hypoxia corresponding to the altitude 6000 m, riboxine promotes the correction of metabolic acidosis, normalization of the ultrastructure of cardiomyocytes and more balanced development of heart hypertrophy.

Topics: Adenosine Triphosphatases; Altitude Sickness; Animals; Cardiomegaly; Dihydrolipoamide Dehydrogenase; Electron Transport Complex IV; Energy Metabolism; Glycogen; Hypoxia; Inosine; L-Lactate Dehydrogenase; Myocardium; Rats; Succinate Dehydrogenase

Dogfish were subjected to acute (80 ppm/24 hours) and subacute (10 ppm/21 days) zinc treatments before measuring the ATP, glycogen, protein, and lactate levels. Acute treatment varies significantly the levels of all the metabolites tested while only protein content is significantly lower after subacute treatment. The results are discussed in relation to the hypoxia effect produced by the metal and the related responses of the fish.

Topics: Adenosine Triphosphate; Animals; Dogfish; Gills; Glycogen; Hypoxia; Lactates; Proteins; Zinc

Cultured adult cardiac myocytes were exposed to anoxia under substrate-free conditions. When compared to the metabolic changes in the oxygen deficient organ, those in the anoxic cell culture proceed in a similar, yet prolonged manner. Release of cytosolic enzymes starts with minor energetic disturbances and proceeds in close correlation to the actual ATP decay. Below 2 mumol ATP/gww, an increasing number of cells becomes irreversibly damaged, but above, 30 min reoxygenation leads to extensive recovery of the whole preparation. The results indicate that leakage of cytosolic enzymes during the early stage of anoxia is due to a gradual protein release from the individual cells, related to reversible membrane alterations.

Topics: Adenosine Triphosphate; Animals; Cells, Cultured; Glucose-6-Phosphate; Glucosephosphates; Glutamate Dehydrogenase; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lactates; Lactic Acid; Malate Dehydrogenase; Myocardium; Phosphocreatine; Rats; Rats, Inbred Strains; Time Factors

Guinea pig heart metabolism was studied in vivo by 13C NMR at 20.18 MHz. High-quality proton-decoupled 13C NMR spectra with excellent signal-to-noise ratios and resolution could be obtained in 6 min. Natural-abundance spectra showed resonances that could be assigned to fatty acids, but glycogen was not seen. During intravenous infusion of D-[1-13C]glucose and insulin, the time course of myocardial glycogen synthesis was followed serially for up to 4 hr. Anoxia resulted in degradation of the labeled glycogen within 6 min and appearance of 13C label in lactic acid. Infusion of sodium [2-13C]acetate resulted in incorporation of label into the C-4, C-2, and C-3 positions of glutamate and glutamine, reflecting "scrambling" of the label expected from tricarboxylic acid cycle activity. Examination of the 31P NMR spectrum of the guinea pig heart in vivo demonstrated no change in the high-energy phosphates during the time periods of the 13C NMR experiments. Our studies indicate that 13C NMR is a unique non-destructive tool for the study of heart metabolism in vivo.

Topics: Acetates; Amino Acids; Animals; Glucose; Glycogen; Guinea Pigs; Hypoxia; Magnetic Resonance Spectroscopy; Myocardium

The general and ultrastructural organization of the heart of the elasmobranch, Scyllium stellare, was studied in normal and in anoxic animals. The rich coronary supply was revealed three-dimensionally by the use of corrosion casts, showing a thebesian system of coronary arterioles and capillaries in the thin, outer compact layer as well as in the predominant, inner spongy layer of trabeculae. Only the sinus venosus received a neuronal input of large bundles of granule-containing axons terminating at fenestrated regions of the endocardium and suggesting a neurohormonal function. A simple, tubular sarcoplasmic reticulum with flattened junctional cisternae was present in myocardial cells of 1-5 microns diameter, which contained one or two bundles of myofibrils. The latter were closely apposed to the inner aspect of the plasmalemma. Mitochondria were located centrally in the cells, which were joined by unfolded desmosomes involving Z-band material. Long periods of anoxia were tolerated without loss of heart function, but at the expense of cytoplasmic glycogen. Lipid granules were abundant in all layers and chambers, notably in animals prepared in the summer. The lipid granules displayed a marked increased in electron density when the heart was incubated in a buffered oxalate solution prior to fixation. A glycogen-sparing effect of the lipids during anoxia was observed.

Topics: Animals; Female; Fishes; Glycogen; Hypoxia; Lipid Metabolism; Microscopy, Electron; Myocardium

Topics: Animals; Body Weight; Female; Glucose Tolerance Test; Glycogen; Hypoxia; Insulin Resistance; Muscles; Rats

The experiments reported here were designed to determine whether stimulating glycogenolysis with theophylline affects the ability of isolated rabbit papillary muscles to sustain and recover from a transient hypoxic episode (15 min). Different substrates [glucose (Glc), pyruvate (Pyr), and butyrate (BA)] were used to either support the glycogen levels or permit their depletion. To evaluate the metabolic consequences, the dynamic relation (coupling coefficient) between the oxidation-reduction level of the intramitochondrial pyridine nucleotide NADH and the mechanical power was determined using a microfluorometer. In the absence of theophylline, the presence of Glc was associated with a smaller decrease in developed tension (tau) during the hypoxic period (Glc 53 +/- 5%) when compared with the nonglycolytic substrates (Pyr 33 +/- 5% or BA 31 +/- 6%). The extent of the recovery was not dependent on the available substrate. The addition of theophylline was accompanied by a substrate-dependent increase in tau: Glc 153 +/- 9%, Pyr 134 +/- 9%, and BA 116 +/- 7%. Theophylline increased the impact of the hypoxic episode on mechanical performance: Glc 17 +/- 4%, Pyr 4 +/- 4%, and BA 6 +/- 5%. With Glc, recovery was comparable to control. For the nonglycolytic substrates, recovery of mechanical function was depressed (Pyr 69 +/- 7%, BA 71 +/- 6%), and there was a significant loss of metabolic sensitivity. These data show that the inotropic response to theophylline is in part determined by the available substrate; theophylline exacerbates the impact of a hypoxic episode, and this effect may be due to the metabolic consequences of its presence.

Topics: Animals; Female; Glycogen; Heart; Heart Ventricles; Hypoxia; In Vitro Techniques; Kinetics; Myocardial Contraction; Myocardium; Rabbits; Theophylline

The pulmonary trunk, muscular arteries, and arterioles of male Sprague-Dawley rats exposed to simulated high altitude hypoxia (380 mm Hg) for six weeks were studied for glycogen localization. As early as three days exposure time, glycogen particles were mobilized in the smooth muscle cells of muscular arteries and arterioles. Weekly sacrifice of animals showed increasing preferential accumulation of glycogen, near the sarcoplasmic reticulum, in the subsarcolemmal region, adjacent to micropinocytotic vesicles, and near the mitochondria in the smooth muscle cells of muscular arteries and arterioles. However, in the smooth muscle cells of the pulmonary trunk and newly muscularized vessels (arteries and arterioles), glycogen storage was not readily noted. These results suggests that the vascular energetics responsible for maintaining the pulmonary hypertensive state differ depending on the class of vessel. Also the muscular pulmonary arteries and arterioles which exhibited the greatest change in glycogen metabolism, may be primarily responsible for the maintenance of pulmonary hypertension.

Topics: Altitude; Animals; Cell Differentiation; Chronic Disease; Glycogen; Hypoxia; Male; Microscopy, Electron; Muscle, Smooth, Vascular; Pulmonary Circulation; Rats; Rats, Inbred Strains

Topics: Animals; Coronary Disease; Glycogen; Hypoxia; In Vitro Techniques; Ligation; Male; Mitochondria, Heart; Myocardium; Perfusion; Rats; Rats, Inbred Strains

Myocardial glycogen mobilization in response to anoxia has been studied in open-chested C57Bl/6NCrl male mice 6 and 24 months of age. During the 1st minute without oxygen, old animals utilized glycogen more rapidly than did young animals. However, during the 2nd minute of anoxia, young animals continued to utilize cardiac glycogen, whereas old animals did not. A direct correlation was noted between glycogen utilization and activation of myocardial phosphorylase activity (A+B forms). Moreover total myocardial phosphorylase declined during anoxia in old animals while showing no significant change in their younger counterparts. This age-related defect in glycogen mobilization suggests altered tolerance to anoxia in aged animals. The inability to mobilize myocardial glycogen may stem from the existence of an altered form of phosphorylase or from an altered environment in the aged heart.

Topics: Aging; Animals; Glycogen; Hypoxia; Male; Mice; Myocardium; Phosphorylases

Topics: Adenosine Monophosphate; Aging; Animals; Blood Glucose; Glycogen; Heart; Heart Rate; Hypoxia; Liver; Liver Glycogen; Male; Mice; Phosphorylase a; Systole

We tested the hypothesis that maternal diabetes is associated with a decreased ability of the newborn to tolerate hypoxia by measuring the time to last gasp of rabbit pups born to diabetic and control does and placed in 100% N2. Rabbits were made diabetic by injection of 100 mg/kg alloxan i.v. The alloxan-treated mothers had significantly elevated blood glucose during pregnancy and at delivery (132 vs. 90 mg/dl, p less than 0.001). Pups were delivered at 30 day's gestation by hysterectomy under local anesthesia. Half of each litter were immediately sacrificed and the remaining pups placed in 100% Ns. The pups from the alloxan-treated mothers showed a higher pre-asphyxial mean blood glucose (97 vs. 73 mg/dl, p less than 0.025) and a lower mean survival time (18.4 vs. 21.1 min, p less than 0.005).

Topics: Animals; Animals, Newborn; Blood Glucose; Body Weight; Diabetes Mellitus, Experimental; Female; Fetal Blood; Glycogen; Heart; Hypoxia; Male; Myocardium; Organ Size; Pregnancy; Pregnancy in Diabetics

Previous studies from this laboratory have demonstrated early and progressive alterations in the ST-T period of the fetal and neonatal electrocardiogram in relation to asphyxia. The aims of the present study were to investigate the metabolic background of these hypoxic ECG changes by means of serial myocardial biopsies in fetal lambs, relating these changes to the hypoxic depletion of glycogen, ATP and creatine phosphate stores in the heart and to the altered myocardial performance as measured by heart rate, mean arterial blood pressure, combined cardiac output and max. dP/dt. The experiments were performed on 21 fetal lambs, acutely exteriorized and subjected to graded hypoxia. During hypoxia there was a significant relationship between the degree of changes in the ST-T period according to a scoring system and the depletion of myocardial glycogen and ATP, a highly significant correlation between the rate of myocardial glycogenolysis and the rate of increase in T wave amplitude, and a parallelism between the amount of glycogen available and fetal cardiovascular function. The myocardium was capable of regenerating its glycogen stores under conditions of adequate oxygenation and in the absence of acidosis and hypoglycaemia.

Topics: Adenosine Triphosphate; Animals; Electrocardiography; Female; Fetal Heart; Glycogen; Heart; Hemodynamics; Hypoxia; Phosphocreatine; Sheep

The ability of endogenous myocardial catecholamines to participate in the development of myocardial cellular alterations during a short period of severe hypoxia (30 min) was studied in isolated, Langendorff-perfused rat heart preparation, arrested by a high potassium concentration (16 mM) and perfused in the absence of exogenous substrate (Table I). Tyramine, which accelerated catecholamine depletion, also increased myocardial cell damage as assessed by a higher lactate dehydrogenase (LDH) release and a more marked reduction in cellular levels of high energy phosphates and glycogen (Table II). On the other hand, under conditions of beta-blockade (atenolol), hypoxia-induced tissular damage was reduced (Table II). These changes could be related to modifications in the cellular content of cyclic AMP (cAMP) since cAMP was consistently higher during the first 30 min of hypoxic perfusion than in control normoxic hearts (Table III) whereas cyclic GMP content remained unchanged. Moreover, interventions increasing cellular content of cAMP (theophylline, dibutyryl-cAMP) also increased hypoxic damage (Table IV), whereas N-methyl imidazole which reduced cellular content of cAMP lessened hypoxia-induced cellular alterations (Table IV). It is concluded that cellular lesions developing during the first 30 min of hypoxia in isolated arrested rat heart preparation perfused without exogenous substrate could be related to intracellular accumulation of cAMP occurring under the effect of endogenous catecholamine release.

Topics: Adenosine Triphosphate; Animals; Atenolol; Catecholamines; Cyclic AMP; Cyclic GMP; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Male; Myocardium; Perfusion; Phosphocreatine; Rats; Time Factors; Tyramine

Topics: Acute Disease; Animals; Coronary Disease; Electrocardiography; Electrophysiology; Energy Metabolism; Glycogen; Heart; Hyperkalemia; Hypoxia; Membrane Potentials; Perfusion; Species Specificity; Swine

Topics: Adenine Nucleotides; Animals; Brain Ischemia; Cerebral Cortex; Energy Metabolism; Glycogen; Hypoxia; Kinetics; Lactates; Phosphocreatine; Potassium; Pyruvates; Rats

Effects of glucose concentration and anoxia upon the metabolite concentrations and rates of glycolysis and respiration have been investigated in the perfused liver of the fetal guinea pig. In most cases the metabolite concentrations in the perfused liver were similar to those observed in vivo. Between 50 days and term there was a fall in the respiratory rate and in the concentration of ATP and fructose 1,6-diphosphate and an increase in the concentration of glutamate, glycogen and glucose. Reducing the medium glucose concentration from 10 mM to 1 mM or 0.1 mM depressed lactate production and the concentration of most of the phosphorylated intermediates (except 6-phosphogluconate) in the liver of the 50-day fetus. This indicates a fall in glycolytic rate which is not in accord with the known kinetic properties of hexokinase in the fetal liver. Anoxia increased lactate production by, and the concentrations of, the hexose phosphates ADP and AMP in the 50-day to term fetal liver, while the concentration of ribulose 5-phosphate, ATP and some triose phosphates fell. These results are consistent with an activation of glycolysis, particularly at phosphofructokinase and of a reduction in pentose phosphate pathway activity, particularly at 6-phosphogluconate dehydrogenase. The calculated cytosolic NAD+/NADH ratio for the perfused liver was similar to that measured in vivo and evidence is presented to suggest that the dihydroxyacetone phosphate/glycerol 3-phosphate ratio gives a better indication of cytosolic redox than the lactate/pyruvate ratio. The present observations indicate that phosphofructokinase hexokinase and possibly pyruvate kinase control the glycolytic rate and that glyceraldehyde-3-phosphate dehydrogenase is at equilibrium in the perfused liver of the fetal guinea pig.

Topics: Adenine Nucleotides; Animals; Aspartic Acid; Citric Acid Cycle; Female; Fructosediphosphates; Gestational Age; Glucose; Glutamates; Glycogen; Glycolysis; Guinea Pigs; Hypoxia; Liver; Male; NAD; NADP; Pentosephosphates; Perfusion; Pregnancy

Topics: Adenosine; Adenosine Deaminase; Animals; Cyclic AMP; Glycogen; Hypoxia; Isoproterenol; Myocardium; Phosphorylases; Rats

Glycolysis was assessed in the isolated foetal Rat in hypoxia. Measurements were made of glucose uptake, lactate output, C14 glucose incorporation into glycogen and tissular levels of ATP, PCr, glycogen and lactate. Glycolysis was stimulated by hypoxia to a greater extent in the young foetal heart of 16.5 days post coitum than in the foetal heart at term. Thus high energy phosphates were maintained at a higher level in the younger heart. The results are discussed in relation to the high resistance to hypoxia of the foetal heart.

Topics: Adenosine Triphosphate; Animals; Female; Fetal Heart; Glucose; Glycogen; Glycolysis; Hypoxia; Lactates; Phosphocreatine; Pregnancy; Rats

Topics: Acetylcholine; Animals; Atropine; Cholinesterase Inhibitors; Female; Glycogen; Heart; Hypoxia; Male; Myocardium; Oxygen Consumption; Rats

Topics: Animals; Brain; Dogs; Energy Metabolism; Female; Glucose; Glycogen; Hypoxia; Ischemia

A transmural myocardial biopsy method was used to study changed in ultrastructure after induced ventricular fibrillation or anoxic arrest in the canine heart. Interstitial edema, mitochondrial derangement, contraction bands, and swelling of capillary endothelium were more extensive in subendocardial than in subepicardial layer after anoxic arrest. Significant numbers of contraction bands were also seen in the myocardium after induced ventricular fibrillation. These changes appeared to be reversible at least in part in the group with induced ventricular fibrillation but generally not in the anoxic arrest animals. After anoxic arrest, preservation of the endocardial layer was significantly poorer than that of the epicardium; after ventricular fibrillation, there appeared to be no such difference. Myocardial mitochondria and glycogen granules were intact and more numerous after ventricular fibrillation than after anoxic arrest. The lesser damage after ventricular fibrillation than after anoxic arrest suggest that the myocardium may be affected less by the no-reflow phenomenon after normal coronary circulation is restored in ventricular fibrillation.

Topics: Animals; Dogs; Glycogen; Heart Arrest; Hemodynamics; Hypoxia; Mitochondria, Heart; Myocardium; Ventricular Fibrillation

Topics: Adenosine Triphosphate; Animals; Coronary Disease; Creatine Kinase; Cytoplasm; Glycogen; Hypoxia; Injections, Subcutaneous; Male; Mitochondria, Heart; Myocardium; Oxygen Consumption; Phosphocreatine; Propranolol; Rabbits; Time Factors

Previous work has shown that rats on high fat (52%) diet (HFD) were hypoxia-resistant compared to rats on carbohydrate (75% CHO) diet (HCD) and on normal diet (ND), as evidenced from their greatly increased survival time on exposure to 10,668 m simulated altitude. Determination of glycogen levels in the heart, skeletal muscle, liver, lungs, and kidneys show that, in hypoxia-susceptible rats, tissue glycogen was decreased in ND and was unchanged in HCD rats. In HFD rats, glycogen in tissues greatly increased on altitude exposure. It is postulated that hypoxia tolerance of HFD rats was enhanced due to: (i) preconditioning to gluconeogenesis and (ii) systemic acidosis caused by their increased fat ingestion.

Topics: Altitude; Animals; Blood Glucose; Brain; Dietary Carbohydrates; Dietary Fats; Glycogen; Hypoxia; Kidney; Liver Glycogen; Lung; Male; Muscles; Myocardium; Rats

Thirty-six anesthetized mongrel dogs were subjected to systemic hypothermia and anoxic cardiac arrest while on cardiopulmonary bypass. Myocardial fine structure in the left ventricle was evaluated by quantitative analysis in the subepicardial, mid-myocardial, and subendocardial layers. The specimens were obtained by a transmural myocardial biopsy method. Graded hypothermia was employed at 36 degrees, 30 degrees, 28 degrees, 25 degrees, and 22 degrees C. The aorta was cross-clamped for 30 minutes at 36 degrees, 30 degrees, 28 degrees, and 25 degrees C. or for 45 minutes at 25 degrees and 22 degrees C. Observations indicated that pathological changes of the myocardial fine structure were significant after anoxic arrest in the normothermic group. Lesions were most extensive in the subendocardial layer after normothermic anoxic arrest, whereas hypothermia below 30 degrees C. preserved the myocardium throughout all layers without difference in pathological changes in the fine structure among the layers. Mitochondria and glycogen granules in the mid-myocardial layer and the subendocardial layer were best preserved with hypothermia at 25 degrees and 22 degrees C. after 30 minutes or 45 minutes of anoxic arrest, and dogs in these groups had a survival rate of 100 percent. Quantitative analysis of ultrastructural changes induced in these experiments suggest that a safe duration of anoxic arrest at 22 degrees to 25 degrees C. is between 30 and 45 minutes.

Topics: Animals; Cardiopulmonary Bypass; Dogs; Glycogen; Heart Arrest, Induced; Heart Ventricles; Hypothermia, Induced; Hypoxia; Mitochondria, Heart; Myocardium

Effects of epinephrine (10(-5) M) on mechanical performance, glycolysis, glycogenolysis, lipolysis, and metabolism of adenine nucleotides were studied in isolated hypoxic rabbit hearts. The exposure of hearts to hypoxia decreased their mechanical performance and heart rate, but increased their utilization of glucose by 50% and the release of lactate by 139%. Myocardial stores of glycogen and ATP declined by 53 and 84%, respectively, but their breakdown products such as lactate, pyruvate, AMP, and inosine accumulated in these hearts. Myocardial content of free fatty acids decreased, and the amount of glycerol increased in hypoxic hearts. Epinephrine stimulated mechanical performance and heart rate of hypoxic hearts, but decreased myocardial glycogen and ATP even more by 62 and 33%, respectively. Though glucose utilization remained unchanged, the release of lactate increased by 66% from hypoxic hearts treated with epinephrine. However, epinephrine failed to stimulate myocardial lipolysis in hypoxic hearts. These metabolic changes due to epinephrine would lead to accelerated depletion of energetic reserves in hypoxic heart and its earlier deterioration.

Topics: Adenine Nucleotides; Animals; Epinephrine; Fatty Acids, Nonesterified; Female; Glucose; Glycerol; Glycogen; Heart Rate; Hypoxia; Inosine; Lactates; Male; Myocardial Contraction; Myocardium; Pyruvates; Rabbits

The behaviour of fuels (glycogen, glucose), of glycolytic pathway intermediates (glucose-6-phosphate, pyruvate) and end-product (lactate), as well as the pool of labile phosphates (ATP, ADP, AMP, creatine phosphate) and the energy charge of the brain were studied in the motor area of the cerebral cortex of beagle dogs. These parameters were evaluated both after various hypoxic conditions (hypoxic hypoxia, hypoxia plus complete or incomplete ischemia) and after 3, 15 or 30 min of post-hypoxic recovery and recirculation. The effect of some drugs (papaverine, UDP-glucose, (-)eburnamonine, suloctidil) following intracarotid perfusion has been evaluated in the various quoted experimental conditions. The tested drugs proved unable to improve the deranged brain metabolism under all the hypoxic conditions. On the contrary, an activating effect of suloctidil and (-)eburnamonine could be observed during the recovery after both hypoxia and hypoxia plus complete ischemia, papaverine being ineffective and UDP-glucose increasing the glycogen synthesis. The drugs proved unable to induce a restitution of the altered brain metabolism after hypoxia plus incomplete ischemia.

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Dogs; Energy Metabolism; Female; Glucose; Glycogen; Hypoxia; Ischemia; Time Factors

We have modeled the energy metabolism of the perfused rat heart in order to elucidate the interaction of physiological and biochemical control mechanisms. This model which includes glycolysis, the Krebs cycle, and related metabolism, contains 68 submodels of individual enzymes and transport mechanisms including both cytosolic and mitochondrial reactions. The method of model construction, which relies heavily on fitting observed in situ behavior to known algebraic rate laws for isolated enzymes, and its data requirements and necessary assumptions are described. Simulation of a CO-induced anoxic preparation is described in detail. Here glycolysis increases sharply, due to both increased glucose uptake and phosphorylase activation (there is rapid interconversion between a and b forms, both of which are active here); this causes a damped glycolytic oscillation originating with the glycogen-handling enzymes rather than phosphofructokinase. The behavior and physiological consequences of ATPase activity and of a lactate permease which exports lactate to the perfusate are discussed.

Topics: Adenine Nucleotides; Animals; Biological Transport; Citric Acid Cycle; Computers; Cytosol; Energy Metabolism; Glucose; Glycogen; Glycolysis; Hydrogen-Ion Concentration; Hypoxia; Lactates; Mitochondria, Muscle; Models, Biological; Myocardium; Perfusion; Pyruvate Dehydrogenase Complex; Pyruvate Kinase; Rats

Topics: Adenosine Triphosphatases; Glycogen; Heart Rate; Histocytochemistry; Humans; Hypoxia; Male; Middle Aged; Muscles; Physical Exertion

Mice on an atherogenic diet for 40 days show a decrease in brain content of catecholamines, cyclic AMP and in dopamine degradation, and modification of the glycolytic pathway. The metabolic changes are paralleled by changes in behaviour, i.e. decrease in spontaneous motor activity and in conditioning avoidance response. The decrease in dopamine degradation and in behaviour parameters is partly due to the propylthiouracil present in the diet. Endovenous treatment with sonicated dispersions of bovine brain phospholipids induces a modification in the parameters of behaviour and metabolism. The possibility is discussed that some of the defects arising during the atherogenic diet are related with the establishment of a hypoxic state.

Topics: Animals; Avoidance Learning; Behavior, Animal; Blood Glucose; Body Weight; Brain; Catecholamines; Cattle; Cholesterol, Dietary; Cyclic AMP; Diet, Atherogenic; Dopamine; Glycogen; Homovanillic Acid; Hypoxia; Lactates; Mice; Motor Activity; Phospholipids; Propylthiouracil; Pyruvates

The content of the free fatty acids, ketone bodies, total glycogen, glucose, adrenaline and noradrenaline and morpho-histochemical picture of the tissues of neuro-endocrinal system (hypophysis and adrenal) in the brain, heart, liver, skeletal muscles and blood of the white non-linear rats, were studied 2-3 min adaptation to complex atmosphere changes: gradual increase of the CO2, decrease of the O2, and cooling (in the condition of deep hypothermia the rectal temperature was--RT--19.1 +/- 0.1 degrees C). The same parameters were studied in 48 hrs after the same training (at normothermia) and in 2-3 min. after the same repeated training in 48 hrs after the first one, at RT--20.2 +/- 0.1 degrees C. The fluctuating character of the metabolism and of the regulating systems was shown.

Topics: Acetoacetates; Acetylcholinesterase; Adrenocorticotropic Hormone; Animals; Brain; Carbohydrate Metabolism; Epinephrine; Fatty Acids, Nonesterified; Glucose; Glycogen; Hypercapnia; Hypothalamo-Hypophyseal System; Hypothermia, Induced; Hypoxia; Lipid Metabolism; Liver; Male; Monoamine Oxidase; Muscles; Myocardium; Norepinephrine; Rats

Topics: Animals; Animals, Laboratory; Arteriosclerosis; Arvicolinae; Body Water; Erythrocyte Count; Female; Glycogen; Housing, Animal; Hypoxia; Leukocyte Count; Life Expectancy; Litter Size; Male; Muscles; Nephritis, Interstitial; Pregnancy; Reproduction; Rodent Diseases; Rodentia

Topics: Adenosine Triphosphate; Animals; Coronary Circulation; Glycogen; Guinea Pigs; Heart Arrest; Heart Arrest, Induced; Hypoxia; Lactates; Lysine; Male; Myocardial Contraction; Potassium; Protein Biosynthesis

Rats were exposed to simulated altitudes of 3658 m, 4877 m, and 7620 m, for 5 h/d for 30 d at an ambient temperature of 28 degrees C. Blood sugar and tissue glycogen levels were measured--after acute exposure and chronic exposure while either fed ad lib or fasted for 24 h--in liver, kidney, brain, heart, lungs, and skeletal muscles. Glycogen levels were decreased significantly in several tissues under chronic hypoxia in fed animals. In the animals which were fasted 24 h before sacrifice after their 1 month altitude exposure, there was a significant glycogen increase in livers but no change in other tissues. In fasted, acute-exposed animals, glycogen decreased in hearts while in other tissues its levels were unchanged. Hyperglycemia invariably accompanied all conditions of altitude exposures (in fed, fasted, acute, or chronic exposed). Glucose injected i.p. to fed rats as single doses of 20 g/kg body weight 3 h before sacrifice resulted in significantly increased glycogen in all tissues except brain. These glucose injected rats had highly increased resistance to hypoxic stress.

Topics: Altitude Sickness; Animals; Blood Glucose; Fasting; Glucose; Glycogen; Hypoxia; Liver Glycogen; Male; Rats; Time Factors

The lung, like other viable organs, requires the adequate supply of oxygen and metabolic substrates for its functional and structural integrity. Therefore, we studied the metabolic and ultrastructural consequences in the canine lung following bronchial and/or pulmonary arterial occlusions. The results indicate that the lung can maintain its bioenergetic levels for 5 hours with either the ventilation or perfusion alone. Ultrastructural changes appear to precede metabolic alterations measured. When both the ventilation and perfusion were interrupted, rapid biochemical and structural deteriorations occurred, whereas the combinations of alveolar obliteration and hypoxemia, induced with low F102, produced intermediate damage. The implications of these findings on the pathogenesis and evolution of acute respiratory distress syndrome, on the lung preservation for transplantation, and on the rationale for membrane oxygenator support are discussed.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Airway Obstruction; Animals; Arterial Occlusive Diseases; Blood Gas Analysis; Blood Glucose; Dogs; Glycogen; Hypoxia; Lactates; Lung; Postoperative Complications; Pulmonary Artery; Pulmonary Edema; Respiratory Distress Syndrome; Ventilation-Perfusion Ratio

Effects of hypoxia and glucose-free solution on the isolated rat portal vein were studied. Decrease of extracellular PO2 below 50 mm Hg caused graded inhibition of spontaneous mechanical activity; below 7 mm Hg, inhibition was complete in most preparations. Contracture force of depolarized portal vein was less sensitive to decreases in PO2. Responses to noradrenaline at all concentrations were markedly depressed at extreme hypoxia. Sucrose-gap experiments showed that hypoxia reduced the spontaneous electrical spike discharge. Mean tissue contents of PCr, ATP and glycogen (expressed as glucose) were 3.02, 2.47 and 5.07 micromol/g cell wt. in spontaneously active control muscles and 1.07, 1.65 and 1.83 after 20 min anoxia. Physiological variations in PO2 may influence myogenic activity of vascular smooth muscle largely through an action at the membrane level and this mechanism may participate in local blood flow control. Caculations indicated that the graded response to hypoxia in the present in vitro experiments was not due to diffusion limitation. Spontaneous mechanical activity was relatively well maintained even after prolonged exposure to glucose-free solution, whereas the responses to K+ and noradrenaline were markedly suppressed. Electrophysiological recordings during spontaneous activity indicated desynchronization and impaired conduction. PCr and ATP were maintained at control levels and glycogen reduced by 50 per cent after 2 h in glucose-free medium. Indications of the use of amino acids (glutamate) as substrate under these conditions were obtained.

Topics: Action Potentials; Adenosine Triphosphate; Animals; Glucose; Glycogen; Hypoxia; Membrane Potentials; Muscle Contraction; Muscle, Smooth; Partial Pressure; Phosphocreatine; Portal Vein; Rats

This study was undertaken to evaluate directly the relationship between evolution of irreversible myocardial injury induced by hypoxia in an isolated papillary muscle preparation and the development of pathophysiological alterations related to severely impaired membrane function. An ionic lanthanum probe technique was employed as a cytochemical marker to monitor the progression of cellular injury, and data from this cytologic technique were correlated with ultrastructure and measurements of contractile parameters in a total of 67 muscles subjected to control conditions or to graded intervals of hypoxia with or without reoxygenation. Marked depression of developed tension and rate of tension development occurred after 30 min of hypoxia. Contractile function showed significant recovery with reoxygenation after 1 h and 15 min of hypoxia but remained depressed when reoxygenation was provided after 2 or 3 h of hypoxia. Examination by transmission and analytical electron microscopy (energy dispersive X-ray microanalysis) revealed lanthanum deposition only in extracellular regions of control muscles and muscles subjected to 30 min of hypoxia. After hypoxic intervals of over 1 h, abnormal intracytoplasmic and intramitochondrial localization of lanthanum were detected. After 1 h and 15 min of hypoxia, abnormal intracellular lanthanum accumulation was associated with only minimal ultrastructural evidence of injury; muscle provided reoxygenation after 1 h and 15 min of hypoxia showed improved ultrastructure and did not exhibit intracellular lanthanum deposits upon exposure to lanthanum during the reoxygenation period. After 2 to 3 h of hypoxia, abnormal intracellular lanthanum accumulation was associated with ultrastructural evidence of severe muscle injury which persisted after reoxygenation. Thus, the data support the conclusion that cellular and membrane alterations responsible for abnormal intracellular lanthanum deposition precede the development of irreversible injury but evolve at a transitional stage in the progression from reversible to irreversible injury induced by hypoxia in isolated feline papillary muscles.

Topics: Animals; Cats; Cell Membrane; Glycogen; Hypoxia; Lanthanum; Methods; Microscopy, Electron; Mitochondria, Muscle; Myocardial Infarction; Myocardium; Myofibrils

Topics: Age Factors; Animals; Chick Embryo; Glycogen; Heart; Hypoxia; Myocardium

Topics: Adenine Nucleotides; Animals; Brain; Creatine; Energy Metabolism; Glucose; Glycogen; Glycolysis; Hypoxia; Ischemia; Kinetics; Male; Mice; Phosphocreatine

The isometric contraction of the isolated rabbit myocardium was measured from 24 days post coitum (dpc) to young adulthood. Tension per gram of heart as developed by the isolated perfused hearts remained constant during late foetal life but increased during the first postnatal week. Sensitivity to hypoxia rapidly increased during foetal life from 26 to 28 days post coitum. In young foetal hearts (up to 28 days post coitum), contraction continued for several hours in the absence of glucose. In contrast, from 28 days post coitum onwards foetal hearts became increasingly dependent on external glucose to maintain their contractility. This change was concomitant with a decrease in myocardial glycogen content. Intracellular electrical activity recorded in the absence of glucose showed that during hypoxia in the foetus at term were reduced, whereas normal activity continued in the same hypoxic glucose-free medium in hearts from foetuses 26 days post coitum. The relative role of glycolysis and oxidative metabolism is discussed and the importance of glycogenolytic metabolism in young isolated foetal hearts is pointed out.

Topics: Animals; Asphyxia Neonatorum; Female; Fetal Hypoxia; Glucose; Glycogen; Heart; Humans; Hypoxia; Infant, Newborn; Myocardial Contraction; Myocardium; Perfusion; Pregnancy; Rabbits

Under significant physical exercises the myocardium of rats displays distinct enzymopathy, increased permeability of the cell membranes with a considerable dispersion of plasma proteins and damage to the ultrastructures of the myocytes. The employment of pyridoxilate reduces the severity of the damaging reaction, and to some extent normalizes the structure of the cellular and sub-cellular elements of the myocardium. This indicates to the prospects of using the regulators of cellular respiration under total and tissue hypoxia.

Topics: Animals; Drug Combinations; Glycerolphosphate Dehydrogenase; Glycogen; Glyoxylates; Heart; Hypoxia; L-Lactate Dehydrogenase; Male; Myocardium; Physical Exertion; Pyridoxine; Pyruvate Decarboxylase; Rats; Succinate Dehydrogenase; Transaminases

Topics: Animals; Calcium; Drug Interactions; Epinephrine; Glycogen; Heart; Hypoxia; In Vitro Techniques; Magnesium; Male; Myocardial Contraction; Myocardium; Phosphates; Phosphorylases; Rats

The effects of hypoxia on different parameters of cell membrane function were studied in 7 and 19 day chick embryonic hearts. The following changes were observed: 1. Transmembrane potential: A depolarization of the cell membrane and a decrease in the duration and in the overshoot of the action potential. 2. Intracellular ion concentrations: A decrease in (K)i and an increase in (Na)i. Cellular Ca-content remained constant. 3. K efflux: An increase in the rate coefficient, which was larger in stimulated preparations. These changes were more pronounced in 19 day than in 7 day hearts. The effects of hypoxia were increased by simultaneous substrate depletion and counteracted by an excess external glucose. We conclude that: 1. The 19 day hearts are more sensitive to oxygen lack than the 7 day hearts. The difference can be correlated with the observation that the younger hearts are able to consume more glycogen during hypoxia. 2. The changes of the resting membrane potential and the overshoot of the action potential correlate with changes in respectively (K)i and (Na)i. 3. An increase in the background K current may be an important factor in explaining the shortening of the action potential during hypoxia.

Topics: Action Potentials; Age Factors; Animals; Calcium; Chick Embryo; Glycogen; Heart; Hypoxia; Membrane Potentials; Myocardium; Potassium; Sodium

Topics: Adenosine Triphosphate; Animals; Creatine Kinase; Glucose; Glycogen; Guinea Pigs; Hypoxia; Lactates; Male; Mice; Myocardium; Perfusion; Rabbits; Rats; Species Specificity

The effects of metabolic accumulation on myocardial metabolism during global heart oxygen deprivation were evaluated in a working in situ swine heart preparation with controlled total coronary blood flow. Myocardial oxygen consumption was depressed to a similar extent by either reducing total coronary flow 60 per cent (ischemia, low coronary perfusion) in 10 swine or by decreasing coronary perfusate PO2 to 30 mm. Hg at normal flows (hypoxemia, high coronary perfusion) in 13 swine. Compared with findings in 13 control hearts, ischemia significantly (p less than 0.05) decreased myocardial oxygen consumption (640 to 390 mumole per hour per gram), glucose uptake (185 to 16 mumole per hour per gram), and free fatty acid consumption (32 to 17 mumole per hour per gram). ttissue levels of glycogen, creatine phosphate, and adenosine triphosphate (tatp) were significantly reduced (p less than 0.005), and tissue lactate, adenosine diphosphate (ADP), and adenosine monophosphate (AMP) were increased (p less than 0.001). During hypoxemia, glucose uptake was increased (240 mumole per hour per gram) and free fatty acid consumption was somewhat less depressed (19 mumole per hour per gram). Creatine phosphate and ATP were higher than with ischemia (p less than 0.01), and lactate, ADP, and AMP accumulations were less (p less than 0.01). Thus, in the period immediately following myocardial oxygen deprivation, inadequate coronary perfusion caused greater metabolic buildup which inhibited myocardial substrate utilization and energy production. High coronary perfusion, even though the perfusate was unoxygenated, was associated with greater preservation of substrate utilization, higher levels of high-energy phosphates, less accumulation of metabolic products, and a longer survival. These data suggest a critical role of coronary perfusion in protecting myocardial metabolism in the immediate period following global heart hypoxia.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Coronary Disease; Disease Models, Animal; Female; Glucose; Glycogen; Heart; Hemodynamics; Hypoxia; Lactates; Male; Myocardial Revascularization; Myocardium; Oxygen Consumption; Phosphocreatine; Swine

Systemic and cerebral metabolic responses to acute anoxia were studied in term-fetal and neonatal rats in order to account for the greater anoxic tolerance of fetuses. Measurements of blood acid-base balance were correlated with changes in the concentrations of adenine nucleotides, creatine, phosphocreatine, and glycogen in brain, and of glucose, pyruvate, and lactate in brain, blood, and cerebrospinal fluid during 1) exposure (20-40 min) to 100% nitrogen at 37 degrees C, and 2) subsequent recovery in air. Blood PCO2 was higher initially in fetuses and increased more rapidly during anoxia in fetuses than in neonates, exceeding 150 mmHg after 20 min. Brain glycogen, phosphocreatine, and total adenine nucleotides declined more slowly in fetuses than in neonates during anoxia, whereas brain glucose levels declined at similar rates in the two groups. From the changes in these preformed and potential energy stores, it was estimated that total cerebral energy consumption during anoxia was significantly lower in fetuses. The data suggest that the more severe hypercapnia superimposed on anoxia in fetuses decreased cerebral metabolic demands, and thus prolonged survival. An incidental finding was that L-lactate readily enters the immature brain from the blood during anoxia, and in the early recovery phase may constitute the preferred substrate for cerebral oxidative metabolism, sparing glucose.

Topics: Adenosine Triphosphate; Animals; Brain; Carbohydrate Metabolism; Creatine; Glucose; Glycogen; Glycolysis; Hypoxia; Lactates; Pyruvates; Rats

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood; Blood Pressure; Cats; Female; Glycogen; Glycolysis; Heart; Heart Rate; Hydrogen-Ion Concentration; Hypoxia; Lactates; Male; Myocardium; Phosphocreatine; Pyruvates

The relationship of glycogen and glucose to anaphylactic histamine release from chopped sensitized guinea pig lung in vitro was studied. A parallelism was observed between the total amount of glycogen in the sensitized lung and the total amount of histamine released from the lung by antigen-antibody reactions. Removal of glucose from the medium for tissue suspension resulted in reduction in histamine release. Depletion of glycogen and/or glucose from the system was associated with (1) abolition of the inhibition of histamine release by isoproterenol and high concentrations of dibutyryl cyclic adenosine monophosphate (AMP) and (2) increase in the rate of enhancement of histamine release by lower concentrations of dibutyryl cyclic AMP. The results indicate that (1) glycogen may be one of the ultimate energy sources for anaphylactic histamine release, and (2) the presence of adequate amounts of glycogen and/or glucose in the sensitized tissue is necessary for the normal beta adrenergic effects on the histamine release in vitro from sensitized lung fragments.

Topics: Anaphylaxis; Animals; Antigen-Antibody Reactions; Cyclic AMP; Glucose; Glycogen; Guinea Pigs; Histamine; Histamine Release; Hypoxia; Immune Sera; In Vitro Techniques; Injections, Intradermal; Isoproterenol; Lung; Male; Ovalbumin; Serum Albumin, Bovine

Topics: Animals; Cats; Eye; Freeze Drying; Glycogen; Haplorhini; Histocytochemistry; Humans; Hypoxia; Macaca mulatta; Periodic Acid; Photoreceptor Cells; Rabbits; Rats; Retina; Staining and Labeling

1. Concentrations of glycogen and of key metabolites have been measured in Cardium edule during aerobic and anaerobic incubation. 2. After 15 hours of anoxia only a slight carbohydrate consumption was found in the whole animal, whereas a decrease in glycogen level seemed evident in the separated adductor muscle. 3. The main end products of the anaerobic carbohydrate breakdown are succinate and alanine which account for 40% and 30% respectively of all accumulated compounds. 4. The concentrations of L-lactate and octopine also increase after 15 hours anaerobic condition, but both are only of minor importance as end products. 5. Propionate is not detectable in the control groups, but accumulates a little during anaerobiosis. The two possible reasons for this low production have been discussed.

Topics: Alanine; Anaerobiosis; Animals; Fatty Acids; Glycogen; Hypoxia; Lactates; Mollusca; Muscles; Species Specificity; Succinates

38 samples of middle ear mucosa were taken from different patients during stapes surgery in otosclerosis. The samples were studied light-and electronmicroscopically without decalcification. Considerable pathologic changes in the organisation of the capillaries (endothelial hydrops, proliferation of the intima and of the adventitia, total obliteration o the vessels) cause pathologic reactions on the mesenchymal elements of the submucosa. Next to fibrolysis or hyalinosis of the collagen fibers the fibrocyts show features of undergoing lysis. Free and cellular bound calcium deposits are located in these lytic areas. The epithelial lining also shows unusual inclusions as glycogen and acid mucopolysaccharides and an alterated basement membrane. We belive that the changes of the connective tissue and of the epithelium are secundary to the capillary obstruction.

Topics: Apatites; Basement Membrane; Blood Vessels; Capillaries; Connective Tissue; Ear; Ear Ossicles; Ear, Middle; Glycogen; Glycosaminoglycans; Humans; Hypoxia; Mucous Membrane; Otosclerosis; Periosteum

Total serum thyroxine levels, saturation of endogenous thyroxine-binding proteins, and free thyroxine indices were all reduced in the rat by aging. In vitro myocardial anoxic resistance was increased as a result of the aging process. The role of myocardial glycogen as a myocardial protective agent during hypoxic stress and its variations during aging, altitude-acclimation, and exericise conditioning are discussed.

Topics: Aging; Animals; Glycogen; Heart; Heart Ventricles; Hypoxia; Male; Myocardium; Rats; Thyroxine; Thyroxine-Binding Proteins

1 The energy dependence of angiotensin and acetylcholine-induced contractions of rat descending colon and uterus was investigated. 2 Differences were observed in the effect of anaerobic substrate depletion upon responses of colon and oestrous and dioestrous uterus. These were attributed to differences in the energy metabolism of the tissues and were correlated with differences in tissue levels of glycogen. 3 The preferential reduction of angiotensin responses of dioestrous uterus and descending colon when exposed to 2,4-dinitrophenol, was evidence for an energy dependent stage in the angiotensin response distinct from the contraction process itself. 4 The absence of a preferential reduction of the angiotensin response of oestrous uterus when exposed to 2,4-dinitrophenol appeared to be related to the ability of this tissue to generate ATP by anaerobic glycolysis. 5 It was concluded that the energy for the angiotensin response may be derived either anaerobically or aerobically, depending upon the tissue.

Topics: Angiotensin II; Animals; Colon; Dinitrophenols; Energy Metabolism; Female; Glucose; Glycogen; Hypoxia; Muscle Contraction; Muscle, Smooth; Rats; Uterus

Topics: Alanine; Anaerobiosis; Animals; Carps; Cyprinidae; Glucose; Glycogen; Hypoxia; Lactates; Liver; Metabolism; Muscles; Oxygen; Oxygen Consumption; Pyruvates; Succinates

Glycogen, adenosine triphosphate, and hydration were measured in rabbit corneal epithelium to determine whether the corneal epithelium glycogen decrease, increase in epithelial hydration, and decrease in epithelial adenosine triphosphate stores, seen as a result of contact lens wear, were secondary only to anoxia or may also have resulted from mild trauma, with no interference to oxygenation. Conventional contact lens wear, trauma, and oxygen-permeable contact lens wear caused metabolic changes, showing trauma as well as anoxia may play an important role in the corneal epithelial response to contact lens wear.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Contact Lenses; Contact Lenses, Hydrophilic; Cornea; Epithelium; Eye Injuries; Glucosephosphate Dehydrogenase; Glycogen; Hexokinase; Hypoxia; L-Lactate Dehydrogenase; Methylmethacrylates; Permeability; Pyruvate Kinase; Rabbits; Silicones; Water-Electrolyte Balance

Levels of ATP are near normal in the cockroach nerve cord when hypoxia is sufficient to cause coma as determined by behavioral observations and nerve cord electrical activity. During anoxia the major change in ATP occurs after loss of measurable nerve activity. High glycogen levels and reduced energy demands due to coma may contribute to the resistance to anoxic death.

Topics: Adenosine Triphosphate; Animals; Central Nervous System; Cockroaches; Coma; Electrophysiology; Glycogen; Hypoxia; Male; Time Factors

The effect of temporary glucose and oxygen deprivation on isometric tension as well as content of glycogen, creatine phosphate (CP), adenosine triphosphate (ATP), adenosine diphosphate (ADP), adenosine monophosphate (AMP), and adenylate pool (AP) were studied in potassium-contracted guinea pig isolated taenia coli. Under aerobic conditions glucose removal caused a decrease in tension, glycogen, CP, ATP, and energy charge; ADP and AMP increased, keeping the adenylate pool size unchanged. During rigor caused by additional anoxia, there was an increase in tension associated with further decrease in ATP and marked reduction of adenylate pool. Restoration of oxygen supply caused only a small increase in ATP that, though sufficient for abolishing rigor, was insufficient to support potassium contraction. Restoration of both glucose and oxygen did not restore tension even though ATP stores were increased further. Elevation of extracellular calcium caused partial restoration of tension, suggesting that the defect was in calcium metabolism rather than energy metabolism. During recovery AP remained low, possibly due to deamination of AMP. Anoxia in the presence of glucose reduced ATP to a concentration similar to that due to aerobic glucose deprivation but tension decreased much less. This result is consistent with different degrees of ATP depletion in various functional (Ca pump vs. contractile mechanism) compartments.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Calcium; Colon; Glucose; Glycogen; Guinea Pigs; Hypoxia; Male; Muscle Contraction; Muscle, Smooth; Oxygen Consumption; Phosphocreatine; Potassium Chloride

Glucose and fatty acid metabolism of resting skeletal muscle were studied by perfusion of the isolated rat hind leg with a hemoglobin-free medium. Tissue integrity was demonstrated by normal ATP, ADP and creatine phosphate levels, by a sufficient oxygen supply, and by a normal appearance of perfused muscle specimens under the electron microscope. The rates of glucose and fatty acid uptake, and of lactate, alanine, glycerol and fatty acid release were constant over a perfusion period of 60 min. Insulin (1 unit/l) caused a more than threefold increase in glucose uptake, a stimulation of lactate production, and a 20% increase in the muscular glycogen levels. Fatty acids and alanine release were significantly diminished by insulin, but glycerol release did not change. The uptake of oleate by the rat hind leg was dependent on the medium concentration in a range of 0.7-1.9mM oleate, and was stimulated by insulin. Glucose uptake was not influenced by oleate, whether sodium was present or not. When the leg was perfused with [1-14C]oleate, 75% of the incorporated fatty acids were found in muscle lipids, 10% were oxidized to CO2, and 5% were recovered in bone lipids. The absolute amount of oleate oxidation was not altered by insulin. In all experiments with and without glucose in the medium, 70-80% of the 14C label incorporated into muscle lipids was found in the triglyceride fraction. In the presence of glucose, insulin significantly increased the incorporation of [1-14C]oleate into muscle triglycerides, whereas no insulin effect, either on fatty acid uptake or on triglyceride formation, could be observed when glucose was omitted from the perfusate. The present results indicate that a "glucose-fatty acid cycle" as found in rat heart muscle does not operate in resting peripheral skeletal muscle tissue. They also demonstrate that the stimulating effect of insulin on muscular fatty acid uptake and triglyceride synthesis is dependent on glucose supply. This finding can be intrepreted as a stimulation of fatty acid esterification by sn-glycerol 3-phosphate derived from an increased glucose turnover, which is in turn due to insulin.

Topics: Animals; Fatty Acids; Glucose; Glycogen; Hypoxia; Insulin; Lactates; Male; Microscopy, Electron; Muscles; Oleic Acids; Perfusion; Rats; Triglycerides

The metabolism of cardiac lipids and glycogen in hypoxic and well-oxygenated perfused rat hearts was studied in the presence or absence of epinephrine. Heart lipids were pre-labeled in vivo with [1-14C]palmitate. Triglyceride disappearance (measured chemically and radiochemically) was observed in well-oxygenated hearts and was stimulated by epinephrine (4.1 X 10(-7)M). Utilization of tissue triglycerides was inhibited in hypoxic hearts in the presence or absence of added epinephrine. Hypoxia resulted in a small increase in tissue 14C-free fatty acids and inhibition of 14C-labeled triglyceride fatty acid oxidation. Epinephrine had no stimulatory effect on fatty acid oxidation in hypoxic hearts. Utilization of 14C-labeled phospholipids (and total phospholipids) was similar in well-oxygenated and hypoxic hearts with or without added epinephrine. These results suggested that the antilipolytic effects of hypoxia were predominant over the lipolytic effects of epinephrine. Glycogenolysis was stimulated threefold by epinephrine in well-oxygenated hearts. Hypoxia alone was a potent stimulus to glycogenolysis. Addition of epinephrine to perfusates of hypoxic hearts resulted in a slight enhancement of glycogenolysis.

Topics: Animals; Carbon Dioxide; Epinephrine; Fatty Acids, Nonesterified; Glucose; Glycogen; Hypoxia; Lipid Metabolism; Male; Myocardium; Oxidation-Reduction; Perfusion; Phospholipids; Rats; Triglycerides

Experiments on isolated functioning hearts of rats established that under equal filling pressure the hearts of the animals who are adapted to the periodic effect of hypoxy develop a higher force and rate of contractions; ultimately, the contractile function of such hearts, as calculated per unit of myocardial mass and unit of time, appears to be increased by 1/3. Oxygen consumption by the hearts of adapted animals does not much differ from the control values, and consequently, the efficiency of oxygen utilization increases approximately by 1/3. A considerable increase of adrenoreactivity of the hearts of adapted animals is also noted. The obtained data are discussed proceeding from the assumption that an increased power of the potassium pump in the sarcoplasmatic reticulum of the myocardium of adapted animals may influence the coupling of oxydation with phosphorillation in the mytochondria.

Topics: Adaptation, Physiological; Animals; Glucose; Glycogen; Heart; Hypoxia; Male; Myocardial Contraction; Myocardium; Oxidative Phosphorylation; Oxygen Consumption; Rats

Adenosine triphosphate (ATP), glycogen, and inorganic phosphorus (Pi) were assayed in myocardial tissues obtained from beating dog hearts subjected to the following procedures: Group 1. Ligation of anterior descending coronary artery(AD) for 60 min. Group 2. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU regular insluin/ml, for 60 min. Group 3. Ligation of the AD for 60 min, followed by release of the ligature with re-establishment of blood flow for 30 min. Group 4. Perfusion of the AD with 20 mM glucose in Ringer's solution containing 1 mU/ml regular insulin for 60 min, followed by re-establishment of blood flow for 30 min. Samples from normal myocardium (N zone) and from the area supplied by the AD (I zone) were simultaneously obtained and the level of metabolites compared. In all four groups, ATP was significantly lower in I than N zone. However, ATP values were lower in N zone in group 1 as compared with the other groups (p less than 0.05) and higher in I zone in group 3 versus groups 1 and 2 (p less than 0.05). Glycogen was lower in I than N zones to a similar degree in all the groups. However, it was higher in the I zone in group 3 than in group 1 (p less than 0.05). Pi was significantly higher in I zone versus N zone only in group 1 (p less than 0.05). These data suggest that, the the beating dog heart, ATP and glycogen preservation in a myocardial segment rendered ischemic for 1 hour is best achieved by re-establishing circulation. Glucose infusion into the ischemic segment did not contribute significantly to the ATP stores in that segment but may have exerted a protective effect on the nonischemic zones, possibly by providing a high glucose level in the circulating blood. This protection was equally well achieved by release of the ligature with or without prior glucose infusion. The increase in Pi in the ischemic zone in the dogs with coronary ligation only is probably related to accumulation of the ion under ischemic and hypoxic conditions.

Topics: Adenosine Triphosphate; Coronary Circulation; Coronary Vessels; Energy Metabolism; Glucose; Glycogen; Heart; Hemodynamics; Hypoxia; Ligation; Myocardium; Perfusion; Phosphates; Phosphorus

The effect of hypoxia, exercise, and thermal stress on myocardial metabolism have been widely investigated, but little attention has been paid to studying the effects of a combination of these stress. The influence of hypoxia as modified by physical exertion (swimming) and cold stress was therefore studied. The parameters investigated included myocardial glycogen and noradrenaline, serum free fatty acid, adrenal ascorbic acid, and adrenal weight. It was observed that maximal stress was produced when hypoxia was combined with physical exertion. No suppression of cold-induced lipolysis by hypoxia was observed, in contrast to previously reported observations. Maximal depletion of cardiac blycogen and cardiac noradrenaline was noted in hypoxic exercise. Adrenal overactivity was not found to be related to any particular stress but was seen to be proportional to the severity of the stress applied.

Topics: Adrenal Glands; Adrenocortical Hyperfunction; Animals; Ascorbic Acid; Cold Temperature; Fatty Acids, Nonesterified; Glycogen; Hypoxia; Lipid Metabolism; Male; Myocardium; Norepinephrine; Organ Size; Physical Exertion; Rats; Stress, Physiological

The mechanism of action of hyperosmolal mannitol was evaluated by hemodynamic and metabolic studies in 79 isovolumic nonrecirculating paced perfused rat hearts during sequential 15-min periods of aerobic, anoxic, and reoxygenated perfusion. Hyperosmolality induced by addition of mannitol significantly decreased myocardial water content (wet/dry wt ratio). It improved recovery of hemodynamic function during reoxygenation. With isomolal perfusion (290 mosmol/kg) left ventricular systolic peak pressure (LVSP) decreased 32% (127 +/- 5 to 86 +/- 6 mmHg) and maximum dP/dt fell 50% (3,513 +/- 328 to 1,758 +/- 172 mmHg/s) during the postanoxic recovery period. With hyperosmolal perfusion (350 mosmol/kg), LVSP decreased 23% (132 +/- 5 to 102 +/- 7 mmHg) and dP/dt fell 21% (3,817 +/- 215 to 2,998 +/- 234 mmHg/s) (P less than .01). Hyperosmolal perfusion did not affect postanoxic total coronary flow, lactate and glucose metabolism, tissue glycogen, creatine phsophate, or adenine nucleotide concentrations. Coronary perfusion with hypersmolal solution aided recovery, enhanced postanoxic myocardial performance, and minimized tissue swelling. The most tenable explanation for the locus of action of hyperosmolal mannitol during anoxia under our experimental conditions is its direct effect on myocardial water content.

Topics: Adenosine Triphosphate; Animals; Coronary Circulation; Glucose; Glycogen; Heart; Hemodynamics; Hypoxia; Lactates; Male; Mannitol; Myocardial Contraction; Myocardium; Osmolar Concentration; Perfusion; Phosphocreatine; Rats; Water

Glycogen is an essential substrate during myocardial anoxia. Since porpranolol may maintain myocardial glycogen levels after acute stress by blockade of catecholamine-induced glycogenolysis, we evaluated the effect of propranolol treatment in the isolated perfused isovolumic paced rat heart. Forty-one rats were studied after 10 min of ice-water immersion: half were pretreated with propranolol, 20 mg/kg/day x3, and half with saline. Glycogen content of unperfused propranolol-treated hearts exceeded controls by 46% (146 +/- 9 vs. 100 +/- 4 mumoles/g dry wt, p less than 0.02), and this difference persisted during aerobic perfusion. Propranolol did not affect adenine nucleotide concentration or left ventricular hemodynamics. Following 5 min of anoxic perfusion, propranolol hearts showed improved ventricular performance concomitant with enhanced glycogenolytic flux and lactate production. Propranolol augmented high energy phosphate production (ATP/AMP = 5.19 +/- 0.42 vs. 3.39 +/- 0.42, p less than 0.02) and increased coronary flow (22.1 +/- 1.6 vs. 16.6 +/- 1.4 ml/min, p less than 0.02) during anoxia. Thus, propranolol supported glycogen stores following acute stresses, enhanced glycogenolytic energy production, increased coronary flow, and improved ventricular function during subsequent anoxia.

Topics: Animals; Catecholamines; Coronary Circulation; Glycogen; Hemodynamics; Hypoxia; Lactates; Male; Myocardium; Perfusion; Phosphates; Propranolol; Rats; Water

The relationship between coronary flow and adenosine triphosphate ATP production was determined in isolated rat hearts and in situ pigs hearts. The major source of ATP in ischemic hearts was oxidative phosphorylation. Oxidation of glucose accounted for most of the residual oxygen consumption in ischemic hearts when the concentration of fatty acids was low, but at 1.2 mM palmitate fatty acids were oxidized in preference to carbohydrate, as in aerobic hearts. The rates of ATP production from both glycolysis and oxidative metabolism were decreased in proportion to the reduction in coronary flow in oxygen-deficient hearts. Glycolysis was reduced to below aerobic rates when coronary flow was about 0.5 ml/min/g tissue in both rat hearts perfused with bicarbonate buffer and blood-perfused pig hearts. Tissue level of high energy phosphates reflected the rates of ATP production and declined in proportion to the reduction in coronary flow. In addition, tissue lactate and H+ accumulated in proportion to the restriction in flow.

Topics: Adenosine Triphosphate; Animals; Coronary Circulation; Coronary Disease; Coronary Vessels; Fatty Acids; Glucose; Glycogen; Glycolysis; Hypoxia; Oxidation-Reduction; Oxidative Phosphorylation; Oxygen Consumption; Palmitates; Perfusion; Rats; Swine

The interaction of hypoxia and catecholamines in the regulation of heart tissue lipid and glycogen utilization was studied in isolated perfused rat hearts with lipids prelabeled in vivo with [1-14C]palmitate. In well oxygenated hearts, epinephrine stimulated triglyceride mobilization by approximately 2-fold. In hypoxia, net mobilization of triglycerides was negligible with or without added epinephrine. Thus, the effect of hypoxia to reduce triglyceride mobilization would favor the accumulation of neutral lipid in the myocardium Glycogenolysis was markedly enhanced in hypoxic hearts and epinephrine produced little further stimulation. In well oxygenated hearts, epinephrine increased glycogen mobilization by 3-fold.

Topics: Animals; Epinephrine; Glycogen; Hypoxia; In Vitro Techniques; Lipid Metabolism; Lipid Mobilization; Male; Myocardium; Palmitic Acids; Rats

Recovery from anoxia has been evaluated in the isovolumic nonrecirculating paced perfused rat heart. Seventy studies were performed consisting of 1) 15 min of aerobic perfusion (AP), 2) AP + 15 min of anoxic perfusion, 3) AP + 15 min of anoxic perfusion + 15 min of reoxygenation. Krebs-Ringer-bicarbonate + 5 mM glucose (KRB) was compared with KRB + mannitol (osmolality, +60 mOsm). Mannitol decreased myocardial water content. It improved recovery of hemodynamic function after reoxygenation. With KRB alone left ventricular systolic peak pressure (LVSp) decreased by 32 percent and maximum dP/dt by 50 percent. With mannitol added LVSp decreased 18 percent and dP/dt 21 percent (p less than 0.01). No effect on energy metabolism was demonstrated. KRB and mannitol did not differentially affect total coronary flow, lactate, and glucose extraction, tissue glycogen, creatine phosphate, or adenine nucleotide concentrations. No significant difference in capillary filling was demonstrated by microfil injection. Mannitol appears to improve LV function by direct myocardial osmotic action unrelated to enhanced energy production.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aerobiosis; Animals; Blood Pressure; Body Water; Glycogen; Heart; Hypoxia; In Vitro Techniques; Mannitol; Myocardium; Osmolar Concentration; Perfusion; Phosphocreatine; Rats

Topics: Adenosine Triphosphate; Animals; Forensic Medicine; Glycogen; Humans; Hypoxia; Lactates; Myocardium; Postmortem Changes; Rabbits; Rats

The glycogen contents of 121 rabbit brains having different levels of hypoxia were determined, calculation being in mg% of glucose per g of brain. It was possible to observe significant reductions in carbohydrate content under conditions of acute and chronic hypoxia. Moderate prepartum accumulation of glycogen in untreated rabbit brains is likely. Chronic reduction in reserve fuel resulted in deficient development of the brain, as is clearly shown by brain weight determinations. This enables a parallel between this condition and intrauterine dystrophia.

Topics: Animals; Animals, Newborn; Brain; Disease Models, Animal; Female; Fetal Hypoxia; Glycogen; Hypoxia; Organ Size; Pregnancy; Rabbits

Topics: Adenosine; Adrenergic beta-Antagonists; Animals; Electrocardiography; Glycogen; Heart; Heart Rate; Hypoxia; Isoproterenol; Propranolol; Propylamines; Rabbits; Solutions; Verapamil

Topics: Adaptation, Physiological; Animals; Blood Glucose; Depression, Chemical; Diving; Fresh Water; Glycogen; Heart Rate; Hypoxia; Lactates; Liver; Liver Glycogen; Myocardium; Succinates; Time Factors; Turtles

Topics: Animals; Epinephrine; Fructose; Glucagon; Glycogen; Glycogen Synthase; Hypoxia; In Vitro Techniques; Lactates; Liver; Male; Perfusion; Phosphorylases; Pyruvates; Rats; Sorbitol; Time Factors

Topics: Animals; Brain; Brain Edema; Brain Neoplasms; Central Nervous System; Dogs; Glycogen; Guinea Pigs; Haplorhini; Hibernation; Humans; Hypoglycemia; Hypoxia; Ischemia; Mice; Microscopy, Electron; Neuroglia; Neurons; Physical Exertion; Rabbits; Radiation Effects; Rats; Seizures; Shock; Starvation

Topics: Adaptation, Physiological; Adenosine Triphosphatases; Animals; Blood Pressure; Coronary Circulation; Electron Transport Complex IV; Glycogen; Heart; Heart Rate; Hypoxia; Lipid Metabolism; Male; Myocardium; Oxygen Consumption; Phosphates; Physical Education and Training; Physical Exertion; Pyruvate Kinase; Rats; Swimming

Topics: Acid Phosphatase; Adenosine Triphosphatases; Alkaline Phosphatase; Animals; Capillary Permeability; Cell Membrane; Cytoplasm; Dogs; Endoplasmic Reticulum; Extracorporeal Circulation; Glucose-6-Phosphatase; Glycogen; Hematocrit; Histocytochemistry; Humans; Hypoxia; Liver; Liver Circulation; Lysosomes; Mitochondria, Liver; Necrosis; Succinate Dehydrogenase

Topics: Adenosine Triphosphate; Anaerobiosis; Brain; Carbohydrate Metabolism; Cyclic AMP; Dietary Carbohydrates; Epinephrine; Glucagon; Gluconeogenesis; Glucose; Glycogen; Glycogen Synthase; Humans; Hyperglycemia; Hypoxia; Insulin; Ketone Bodies; Lactates; Liver; Muscles; Oxidative Phosphorylation; Physical Exertion; Postoperative Complications; Pyruvates; Starvation; Wounds and Injuries

Topics: Animals; Carbon Dioxide; Glucagon; Glycogen; Heart; Heart Rate; Hypoxia; In Vitro Techniques; Male; Perfusion; Rats; Transducers

Topics: Acid-Base Equilibrium; Adrenal Glands; Animals; Animals, Newborn; Catecholamines; Female; Fetus; Glycogen; Glycolysis; Hypoxia; Lactates; Liver; Myocardium; Pregnancy; Pyruvates; Rabbits

Topics: Adenosine Triphosphate; Animals; Glucose; Glycogen; Heart; Heart Diseases; Hypoxia; Isoproterenol; Lactates; Male; Myocardium; Necrosis; Perfusion; Phosphocreatine; Rats; Time Factors

Topics: Animals; Cornea; Edema; Epithelial Cells; Epithelium; Eye Diseases; Glycogen; Histocytochemistry; Hypoxia; L-Lactate Dehydrogenase; Microscopy, Phase-Contrast; Rabbits

Topics: Animals; Cardiac Output; Coronary Circulation; Dogs; Electric Countershock; Energy Metabolism; Extracorporeal Circulation; Glucose; Glycogen; Heart Arrest; Hemodynamics; Hypoxia; Oxygen Consumption; Perfusion; Potassium; Resuscitation; Sodium; Time Factors; Ventricular Function

Topics: Animals; Cardiac Output; Coronary Disease; Disease Models, Animal; Dogs; Edema; Electrocardiography; Endoplasmic Reticulum; Glycogen; Heart; Hypoxia; Microscopy, Electron; Mitochondrial Swelling; Myocardial Revascularization; Myocardium; Myofibrils; Thoracic Arteries

Topics: Adenosine Triphosphate; Adult; Biopsy, Needle; Energy Metabolism; Glucose; Glycogen; Humans; Hypoxia; Lactates; Male; Muscles; Oxygen; Oxygen Consumption; Phosphocreatine; Physical Exertion; Pyruvates; Time Factors

Topics: Accidents, Aviation; Aerospace Medicine; Arrhythmias, Cardiac; Glycogen; Humans; Hypoxia; Lactates; Myocardium; Postmortem Changes; Potassium; United States

Topics: Adaptation, Physiological; Aging; Animals; Asphyxia; Brain; Caniformia; Diving; Female; Fetus; Glycogen; Hypoxia; Male; Muscles; Myocardium; Organ Specificity; Pregnancy; Species Specificity

Topics: Animals; Brain; Glycogen; Haplorhini; Hypoxia; Kidney; Liver Glycogen; Macaca; Muscles; Spleen; Starvation; Time Factors

Topics: Adenosine Triphosphatases; Animals; Body Weight; Carbohydrate Metabolism; Cardiac Output; Coronary Vessels; Energy Metabolism; Fatty Acids, Nonesterified; Glycogen; Heart; Hypoxia; Myocardium; Organ Size; Oxygen Consumption; Physical Conditioning, Animal; Physical Fitness; Rats; Regional Blood Flow

Topics: Adult; Animals; Cardiomegaly; Cell Nucleus; Dogs; Endocardial Fibroelastosis; Glycogen; Heart Arrest; Heart Diseases; Heart Failure; Humans; Hypoxia; Male; Middle Aged; Mitochondria, Muscle; Myocardium; Tetralogy of Fallot; Wolff-Parkinson-White Syndrome

Topics: Animals; Arteries; Carbon Dioxide; Coronary Circulation; Coronary Vessels; Cyclic AMP; Enzyme Activation; Epinephrine; Glucosyltransferases; Glycogen; Hypoxia; Ischemia; Male; Myocardium; Nitrogen; Oxygen; Phosphorylase Kinase; Phosphorylases; Practolol; Rats; Time Factors

Topics: Animals; Cornea; Epithelial Cells; Epithelium; Female; Glycogen; Histocytochemistry; Hypoxia; L-Lactate Dehydrogenase; Male; Rabbits

Topics: Animals; Body Temperature; Bradycardia; Cold Temperature; Cricetinae; Glycogen; Helium; Hypothermia, Induced; Hypoxia; Liver Glycogen; Myocardium; Norepinephrine; Oxygen; Partial Pressure; Rectum; Time Factors

Topics: Amines; Animals; Basal Ganglia; Brain; Brain Chemistry; Carbohydrate Metabolism; Caudate Nucleus; Corpus Striatum; Diencephalon; Dopamine; Glucose; Glycogen; Hypoxia; Lactates; Male; Norepinephrine; Rats; Serotonin; Telencephalon

Topics: Animals; Dogs; Glycogen; Heart; Hypoxia; Myocardium

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Aorta, Thoracic; Culture Media; Culture Techniques; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Lactates; Muscle Contraction; Muscle, Smooth; Phenylephrine; Phosphocreatine; Pyruvates; Rabbits

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Biological Transport; Blood Circulation; Blood Pressure; Carbohydrate Metabolism; Cell Membrane Permeability; Coronary Vessels; Glucose; Glucosephosphates; Glycogen; Glycolysis; Hypoxia; Insulin; Ischemia; Lactates; Myocardium; Perfusion; Phosphocreatine; Pyruvates; Rats

Topics: Adaptation, Physiological; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Coronary Disease; Glycogen; Hypoxia; Male; Myocardium; Phosphates; Physical Exertion; Rats

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Dogs; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Intestine, Small; Lactates; Liver; Lung; Muscles; Oxygen Consumption; Shock, Hemorrhagic; Shock, Septic; Splenectomy

Topics: Adenine Nucleotides; Animals; Denervation; Glycogen; Heart; Hypoxia; Lactates; Myocardium; Phosphates; Phosphocreatine; Rabbits; Reserpine

Topics: Delivery, Obstetric; Erythroblastosis, Fetal; Female; Fetus; Glucose; Glycogen; Humans; Hypoglycemia; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Labor, Obstetric; Lipid Metabolism; Maternal-Fetal Exchange; Oxygen Consumption; Pregnancy; Pregnancy in Diabetics

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Blood Glucose; Blood-Brain Barrier; Brain; Brain Chemistry; Glucose; Glycogen; Glycolysis; Hypoglycemia; Hypoxia; Lactates; Liver; Mice; Phosphocreatine; Time Factors

Topics: Animals; Biopsy; Carbon; Carbon Dioxide; Cholesterol; Glucose; Glycogen; Hypoxia; Lactates; Lipid Metabolism; Male; Muscles; Organ Size; Oxygen; Phospholipids; Proteins; Rats; Succinate Dehydrogenase

Topics: Animals; Blood Glucose; Carbon Monoxide Poisoning; Glycogen; Hypoxia; Male; Rats; Vibration

Topics: Adaptation, Physiological; Age Factors; Animals; Glycogen; Hypoxia; L-Lactate Dehydrogenase; Lactates; Rats; Time Factors

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Bivalvia; Carbohydrate Metabolism; Glycogen; Glycolysis; Hypoxia; Oxygen Consumption; Time Factors

Topics: Animals; Dogs; Glucose; Glycogen; Hypoxia; Lactates; Myocardium

Topics: Adaptation, Physiological; Adenosine Triphosphate; Aerobiosis; Animals; Biological Transport; Carbohydrate Metabolism; Energy Transfer; Fatty Acids; Glycogen; Humans; Hypoxia; Lactates; Metabolism; Mitochondria, Muscle; Muscles; Myoglobin; Oxidative Phosphorylation; Oxygen Consumption; Phosphocreatine; Physical Exertion; Regional Blood Flow; Respiration

Topics: Acid-Base Equilibrium; Delivery, Obstetric; Female; Fetal Blood; Fetal Distress; Glucose; Glycogen; Humans; Hydrogen-Ion Concentration; Hypoxia; Maternal-Fetal Exchange; Oxygen Consumption; Partial Pressure; Pregnancy; Time Factors

Topics: Adenosine Triphosphate; Animals; Creatine Kinase; Glucose; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Heart; Hypoxia; In Vitro Techniques; Lactates; Myocardium; Phosphates; Phosphocreatine; Phosphotransferases; Potassium; Rats

Topics: Adaptation, Physiological; Adult; Altitude; Animals; Bolivia; Disease Models, Animal; Glucose; Glycogen; Heart Diseases; Hexosephosphates; Humans; Hypoxia; Lactates; Oxygen Consumption; Peru; Pyruvates; Rats

Topics: Adaptation, Physiological; Animals; Cardiomegaly; Glycogen; Hypoxia; Myocardium; Rats

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Blood Glucose; Brain; Carbon Isotopes; Chickens; Citrates; Cyclic AMP; Dietary Carbohydrates; Fructosephosphates; Galactose; Glucose; Glucosephosphates; Glycerophosphates; Glycogen; Glycolysis; Hypoxia; Ischemia; Kinetics; Lactates; Male; Neurons; Phosphocreatine; Tritium

Topics: Adenosine Triphosphate; Animals; Anura; Azides; Biological Transport; Carbohydrate Metabolism; Dinitrophenols; Fluorine; Fructosephosphates; Glucosephosphates; Glycogen; Hypoxia; In Vitro Techniques; Iodoacetates; Lactates; Methods; Muscles; Nitrobenzenes; Rana temporaria; Sodium; Trioses; Xylose

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Dicarboxylic Acids; Glycogen; Heart; Hypoxia; Myocardium; Nitrobenzenes; Nitroglycerin; Phosphocreatine; Pyridines; Rabbits; Vasodilator Agents

Topics: Analysis of Variance; Female; Gestational Age; Glycogen; Glycogen Synthase; Humans; Hypoxia; Organ Culture Techniques; Phosphorylases; Placenta; Pregnancy

Topics: Adenosine Triphosphate; Animals; Arrhythmias, Cardiac; Bradycardia; Coronary Circulation; Dextrans; Electrocardiography; Erythrocyte Aggregation; Glucosyltransferases; Glycogen; Heart; Hypoxia; Microcirculation; Mitochondria, Muscle; Myocardium; Oxidative Phosphorylation; Phosphocreatine; Rabbits; Rats; Vasopressins

Topics: Animals; Biomechanical Phenomena; Glucose; Glycogen; Glycolysis; Heart Ventricles; Hypoxia; In Vitro Techniques; Iodoacetates; Rats; Species Specificity; Temperature; Time Factors; Turtles

Studies with the isolated perfused working rat heart were carried out to investigate factors that may enable the heart to recover after periods of anoxia. It was found that the presence of glucose in the perfusion fluid during anoxia was essential for complete post-anoxic recovery and the presence of a high concentration of K(+) increased not only the rate of recovery but also the final extent of recovery. In an attempt to clarify the roles played by glucose and K(+) in aiding the survival and recovery of the anoxic myocardium the concentrations of parameters associated with energy liberation and anaerobic glycolysis (ATP, ADP, AMP, P(i), creatine phosphate, glycogen and lactate) were measured in the presence and absence of glucose during the anoxic phase. Determinations of these parameters were carried out during the working aerobic control period, the anoxic period (K(+) arrest) and the recovery period. The results demonstrated that glucose acted as an energy source during anoxia and thus maintained myocardial concentrations of high-energy phosphates, particularly ATP. These studies have also shown a direct relationship between the ability of the heart to recover and the concentration of myocardial ATP at the time of reoxygenation.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Glucose; Glycogen; Glycolysis; Heart; Hypoxia; In Vitro Techniques; Lactates; Male; Myocardium; Oxygen; Perfusion; Phosphocreatine; Potassium; Rats

Topics: Acute Disease; Adaptation, Physiological; Animals; Brain; Cerebral Cortex; Chronic Disease; Glycogen; Glycolysis; Hypoxia; Medulla Oblongata; Mice; Rats; Time Factors

Topics: Age Factors; Animals; Animals, Newborn; Glucose; Glycogen; Heart Ventricles; Hydrogen-Ion Concentration; Hypoxia; Muscle Contraction; Myocardium; Oxygen Consumption; Papillary Muscles; Perfusion; Phosphorylases; Rabbits; Temperature

Topics: Adaptation, Physiological; Animals; Brain; Carbon Monoxide Poisoning; Glucose; Glycogen; Hypoxia; Male; Muscles; Rats; Vibration

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Brain; Cerebral Cortex; Electrodes, Implanted; Electroencephalography; Glucose; Glycogen; Hypothalamus; Hypoxia; Ischemia; Lactates; Male; Phosphocreatine; Pyruvates; Rats; Telemetry; Time Factors

Topics: Animals; Blood Glucose; Catecholamines; Cyprinidae; Epinephrine; Glucose; Glucosyltransferases; Glycogen; Hypoxia; Insulin; Lactates; Liver; Muscles; Myocardium

Topics: Animals; Cardiac Output; Dogs; Extracorporeal Circulation; Glucose; Glycogen; Heart Arrest; Hypoxia

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Catecholamines; Cations, Divalent; Dogs; Glycogen; Heart; Hydrogen-Ion Concentration; Hydrolysis; Hypothermia, Induced; Hypoxia; In Vitro Techniques; Myocardium; Perfusion; Phosphocreatine

Topics: Adenosine Triphosphate; Animals; Cytoplasm; Dogs; Glycogen; Heart; Humans; Hypoxia; Lactates; Mitochondria, Muscle; Models, Biological; Myocardium; Oxygen; Oxygen Consumption; Phosphocreatine; Reserpine

Topics: Animals; Cornea; Densitometry; Epithelium; Glycogen; Hypoxia; Rabbits

Topics: Anaerobiosis; Animals; Arrhythmias, Cardiac; Blood Glucose; Disease Models, Animal; Dogs; Fatty Acids, Nonesterified; Glucose; Glycogen; Glycolysis; Humans; Hypoxia; Insulin; Lactates; Myocardial Infarction; Myocardium; Rats

Topics: Adenosine Triphosphate; Animals; Blood Pressure; Body Weight; Cardiac Output; Coronary Circulation; Glycogen; Heart; Hypoxia; Lactates; Male; Myocardium; Oxygen; Oxygen Consumption; Partial Pressure; Phosphocreatine; Physical Education and Training; Pyruvates; Rats; Rats, Inbred Strains; Time Factors

Topics: Blood; Cleft Lip; Glycogen; Glycolysis; Heart Diseases; Humans; Hypoxia; Immunization, Passive; Oxygen Consumption

Topics: Amylases; Animals; Dogs; Extracorporeal Circulation; Glycogen; Heart Arrest; Histocytochemistry; Hypoxia; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Time Factors

Topics: Age Factors; Carbon Isotopes; Dinitrophenols; Female; Glucosyltransferases; Glycogen; Humans; Hypoxia; Methods; Organ Culture Techniques; Organ Size; Oxygen; Phosphorylases; Placenta; Pregnancy

Topics: Adaptation, Physiological; Altitude; Carbon Dioxide; Cell Nucleus; Chronic Disease; Coronary Circulation; Coronary Disease; DNA; Genetic Code; Glycogen; Heart; Humans; Hypoxia; L-Lactate Dehydrogenase; Mitochondria, Muscle; Myocardium; Myofibrils; Oxygen Consumption; RNA; Succinate Dehydrogenase

Topics: Adenine Nucleotides; Animals; Cholesterol; Coronary Circulation; Creatine; Electric Stimulation; Electrocardiography; Fatty Acids, Nonesterified; Glycogen; Heart; Heart Rate; Hydrogen-Ion Concentration; Hypoxia; In Vitro Techniques; Lactates; Male; Mitochondria, Muscle; Muscle Contraction; Myocardium; Norepinephrine; Perfusion; Phosphates; Phosphocreatine; Phospholipids; Rats; Triglycerides

Topics: Adenosine Triphosphate; Anaerobiosis; Animals; Blood Glucose; Blood-Brain Barrier; Brain; Fluorometry; Fructose; Glucose; Glycogen; Hexokinase; Hypoglycemia; Hypoxia; Insulin; Ischemia; Kinetics; Mice; Permeability; Phosphocreatine

Topics: Animals; Glucose; Glycogen; Heart; Hypoxia; Iodoacetates; Isoproterenol; Male; Methods; Muscle Contraction; Myocardium; Oxygen; Rats; Rats, Inbred Strains; Time Factors

Topics: Animals; Carbohydrate Metabolism; Carbon Isotopes; Cholesterol; Fatty Acids, Nonesterified; Glucose; Glycerophosphates; Glycogen; Heart Rate; Hypoxia; Lactates; Myocardium; Oxygen Consumption; Palmitic Acids; Perfusion; Phospholipids; Rats; Species Specificity; Triglycerides; Turtles

Topics: Adenine Nucleotides; Age Factors; Anaerobiosis; Animals; Animals, Newborn; Brain Chemistry; Glycogen; Glycolysis; Hypoxia; Ischemia; Kidney; Myocardium; Oxygen Consumption; Phosphocreatine; Rabbits

Topics: Animals; Brain; Carbon Dioxide; Cats; Cerebellum; Cerebral Cortex; Diencephalon; Female; Glycogen; Hypoxia; Male; Medulla Oblongata; Mesencephalon; Oxygen; Pons

Topics: Adenosine Triphosphate; Animals; Cardiomegaly; Disease Models, Animal; Glycogen; Glycolysis; Heart; Heart Failure; Heart Rate; Hypoxia; In Vitro Techniques; Lactates; Male; Methods; Mitochondria, Muscle; Myocardium; Phosphorylases; Rats; Time Factors

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Carbon Isotopes; Cobalt; Coenzyme A; Edetic Acid; Glycogen; Hot Temperature; Hypoxia; Kinetics; Magnesium; Manganese; Myocardium; NAD; Nucleotidases; Protein Denaturation; Rats; Spectrophotometry

Topics: Acetylcholinesterase; Animals; Catecholamines; Cricetinae; Electron Transport Complex IV; Esterases; Fasting; Female; Fructose-Bisphosphate Aldolase; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Heart Conduction System; Hydroxybutyrate Dehydrogenase; Hypoxia; Isocitrate Dehydrogenase; Isoenzymes; L-Lactate Dehydrogenase; Lysosomes; Malate Dehydrogenase; Male; Mice; Myocardium; Oxidoreductases; Phosphoric Monoester Hydrolases; Rats; Sinoatrial Node; Succinate Dehydrogenase; Synaptic Transmission

1. Two-day-old rats were exposed at constant temperature to atmospheres containing air and nitrogen with the air content varied in steps from 100 to 0%. By using this system of graded hypoxia a comparison was made between rates of gluconeogenesis from lactate, serine and aspartate in the whole animal and the concentrations of several liver metabolites. 2. Gluconeogenesis, expressed as the percentage incorporation of labelled isotope into glucose plus glycogen, proceeds linearly for 30min when the animals are incubated in a normal air atmosphere, but is completely suppressed if the atmosphere is 100% nitrogen. 3. Preincubation of animals for between 5 and 30min under an atmosphere containing 19% air results in the attainment of a new steady state with respect to gluconeogenesis and hepatic concentrations of ATP, ADP, AMP, lactate, pyruvate, beta-hydroxybutyrate and acetoacetate. 4. When lactate (100mumol), aspartate (20mumol) or serine (20mumol) was injected, it was shown that the more severe the hypoxia the greater the depression of gluconeogenesis. Under conditions when gluconeogenesis was markedly inhibited there were no changes in the degree of phosphorylation of hepatic adenine nucleotides, but free [NAD(+)]/[NADH] ratios fell in both cytosol and mitochondrial compartments of the liver cell. 5. Measurements of total liver NAD(+) and NADH showed that the concentrations of these nucleotide coenzymes changed less with anoxia, in comparison with the concentration ratio of free coenzymes. 6. Calculations showed that the difference in NAD(+)-NADH redox potentials between mitochondrial and cytosol compartments increased with the severity of hypoxia. 7. From the constancy of the concentrations of adenine nucleotides it is concluded that liver of hypoxic rats can conserve ATP by lowering the rate of ATP utilization for gluconeogenesis. Gluconeogenesis may be regulated in turn by the changes in mitochondrial and cytosol redox state.

Topics: Acetoacetates; Adenine Nucleotides; Adenosine Triphosphate; Animals; Aspartic Acid; Gluconeogenesis; Glucose; Glycogen; Hydroxybutyrates; Hypoxia; Lactates; Liver; Mitochondria, Liver; NAD; Pyruvates; Rats; Serine; Time Factors

Topics: Animals; Brain; Cerebrovascular Circulation; Cyclic AMP; Dogs; Glycogen; Hypoxia

Topics: Adenosine Triphosphate; Animals; Blood Glucose; Glucose; Glycogen; Hypoxia; Insulin; Insulin Secretion; Ischemia; Islets of Langerhans; Male; Phosphocreatine; Rats; Tolbutamide

Topics: Animals; Basement Membrane; Dendrites; Endoplasmic Reticulum; Female; Ganglia, Autonomic; Glycogen; Golgi Apparatus; Hypoxia; In Vitro Techniques; Lysosomes; Male; Microscopy, Electron; Mitochondria; Nerve Endings; Nerve Fibers, Myelinated; Rats; Stellate Ganglion; Time Factors

Topics: Acid Phosphatase; Animals; Brain; Cerebral Cortex; Cerebrovascular Disorders; Disease Models, Animal; Glucuronidase; Glycogen; Hemiplegia; Hydrolases; Hypoxia; Hypoxia, Brain; Ischemic Attack, Transient; Lysosomes; Male; Mitochondria; Rats

Topics: Animals; Cricetinae; Epinephrine; Female; Glycogen; Heart; Heart Ventricles; Helium; Hypothermia, Induced; Hypoxia; Male; Myocardium; Norepinephrine

Topics: Acetone; Adenine Nucleotides; Adenosine Triphosphate; Animals; Blood Flow Velocity; Blood Pressure; Cardiac Output; Citrates; Glycerophosphates; Glycogen; Glycolysis; Heart; Heart Atria; Heart Rate; Hexosephosphates; Hypoxia; In Vitro Techniques; Myocardium; Oxygen Consumption; Perfusion; Phosphates; Pyruvates; Rats; Time Factors; Trioses

Topics: Female; Fetal Diseases; Glycogen; Histocytochemistry; Humans; Hypoxia; Infant, Newborn; Infant, Newborn, Diseases; Neutrophils; Pregnancy

Topics: Coronary Circulation; Eisenmenger Complex; Glycogen; Heart; Humans; Hypoxia; Isoenzymes; Kinetics; L-Lactate Dehydrogenase; Lactates; Myocardium; Oxygen Consumption; Phospholipids; Pyruvates; Tetralogy of Fallot; Triglycerides

Topics: Animals; Capillaries; Cell Nucleus; Coronary Disease; Electron Transport; Glycogen; Heart; Hypoxia; In Vitro Techniques; Lipid Metabolism; Mitochondria, Muscle; Myocardium; Myofibrils; Oxidative Phosphorylation; Rabbits; Sarcoplasmic Reticulum

Topics: Acidosis; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Cardiac Surgical Procedures; Dogs; Fructosephosphates; Glucose; Glycogen; Heart Arrest; Heart Rate; Hematocrit; Hemoglobins; Hydrogen-Ion Concentration; Hypoxia; Lactates; Methods; Myocardium; Oxygen Consumption; Perfusion; Phosphates; Potassium; Water-Electrolyte Balance

1. In aerobic conditions the isolated perfused liver from well-fed rats rapidly formed lactate from endogenous glycogen until the lactate concentration in the perfusion medium reached about 2mm (i.e. the concentration of lactate in blood in vivo) and then production ceased. Pyruvate was formed in proportion to the lactate, the [lactate]/[pyruvate] ratio remaining between 8 and 15. 2. The addition of 5mm- or 10mm-glucose did not affect lactate production, but 20mm- and 40mm-glucose greatly increased lactate production. This effect of high glucose concentration can be accounted for by the activity of glucokinase. 3. The perfused liver released glucose into the medium until the concentration was about 6mm. When 5mm- or 10mm-glucose was added to the medium much less glucose was released. 4. At high glucose concentrations (40mm) more glucose was taken up than lactate and pyruvate were produced; the excess of glucose was probably converted into glycogen. 5. In anaerobic conditions, livers of well-fed rats produced lactate at relatively high rates (2.5mumol/min per g wet wt.). Glucose was also rapidly released, at an initial rate of 3.2mumol/min per g wet wt. Both lactate and glucose production ceased when the liver glycogen was depleted. 6. Addition of 20mm-glucose increased the rate of anaerobic production of lactate. 7. d-Fructose also increased anaerobic production of lactate. In the presence of 20mm-fructose some glucose was formed anaerobically from fructose. 8. In the perfused liver from starved rats the rate of lactate formation was very low and the increase after addition of glucose and fructose was slight. 9. The glycolytic capacity of the liver from well-fed rats is equivalent to its capacity for fatty acid synthesis and it is pointed out that hepatic glycolysis (producing acetyl-CoA in aerobic conditions) is not primarily an energy-providing process but part of the mechanism converting carbohydrate into fat.

Topics: Animals; Coenzyme A; Fatty Acids; Female; Fructose; Glucokinase; Glucose; Glycogen; Glycolysis; Hypoxia; In Vitro Techniques; Lactates; Liver; Male; Perfusion; Pyruvates; Rats; Starvation

Topics: Analysis of Variance; Animals; Chlorides; Choline; Dinitrophenols; Epithelial Cells; Epithelium; Glycogen; Heart Ventricles; Hypoxia; Intestinal Mucosa; Intestine, Small; Muscle, Smooth; Muscles; Seasons; Turtles; Urinary Bladder

Topics: Action Potentials; Adenosine Triphosphate; Animals; Anura; Culture Techniques; Electric Stimulation; Glucose; Glucosephosphates; Glycogen; Hypoxia; Lactates; Oxygen; Phosphocreatine; Potassium; Pyruvates; Rabbits; Rana pipiens; Sciatic Nerve

Topics: Altitude; Animals; Blood Glucose; Blood Urea Nitrogen; Body Weight; Diaphragm; Disease Models, Animal; Glycogen; Hypoxia; Insulin; Lactates; Liver; Liver Glycogen; Male; Myocardium; Organ Size; Phenformin; Pyruvates; Rats

Topics: Acclimatization; Altitude; Animals; Glycogen; Glycolysis; Hypoxia; Male; Myocardium; Rats

Topics: Adenosine Triphosphate; Animals; Brain; Brain Chemistry; Fluorometry; Freezing; Glucose; Glycogen; Hypoxia; Ischemia; Lactates; Male; Mice; Phosphocreatine; Seizures; Time Factors

Topics: Acetylcholine; Adenine Nucleotides; Adenosine Triphosphate; Animals; Calcium; Calcium Isotopes; Dogs; Glycogen; Hypoxia; Kinetics; Muscle, Smooth; Phosphocreatine; Trachea

Topics: Adenine Nucleotides; Animals; Glucose; Glycogen; Hemorrhage; Hypoxia; Ischemia; Lactates; Myocardium; Phosphates; Postmortem Changes; Rabbits

Topics: Adolescent; Adult; Aged; Animals; Autopsy; Cell Membrane; Child; Electromyography; Female; Glycogen; Histology, Comparative; Humans; Hypoxia; Larynx; Lipids; Male; Mammals; Microscopy, Electron; Middle Aged; Mitochondria, Muscle; Muscle Contraction; Muscles; Myofibrils; Staining and Labeling; Temperature

Topics: Adenosine Triphosphate; Animals; Curare; Electron Transport Complex IV; Glycogen; Hypoxia; Lactates; Magnesium; Muscles; Myoglobin; Nitrogen; Oxygen; Phosphocreatine; Stress, Physiological; Succinate Dehydrogenase; Swine

Topics: Animals; Axons; Catecholamines; Cytoplasmic Granules; Female; Glycogen; Hypoxia; Iris; Male; Microscopy, Electron; Microscopy, Fluorescence; Nerve Fibers, Myelinated; Neurons; Norepinephrine; Rabbits; Sympathectomy; Time Factors

Topics: Adipose Tissue, Brown; Animals; Body Weight; Brain Chemistry; Chorionic Gonadotropin; Disease Models, Animal; Female; Fetus; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Lactates; Lipids; Liver Glycogen; Myocardium; Organ Size; Placenta; Placenta Diseases; Pregnancy; Pregnancy, Prolonged; Rabbits

Topics: Animals; Cardiac Glycosides; Catecholamines; Glucagon; Glucose; Glycogen; Glycolysis; Guinea Pigs; Heart; Histamine; Humans; Hypercalcemia; Hypocalcemia; Hypoxia; Insulin; Lipid Metabolism; Musculoskeletal System; Myocarditis; Myocardium; Rabbits; Rats; Thyroxine

Topics: Adipose Tissue; Air; Altitude; Animals; Diet; Fasting; Fatty Acids, Nonesterified; Glycerol; Glycogen; Hypoxia; Lactates; Male; Norepinephrine; Rats

Topics: Altitude; Amino Acids; Animals; Blood Glucose; Carboxy-Lyases; Erythrocytes; Fasting; Gluconeogenesis; Glutamine; Glycerol; Glycogen; Homeostasis; Hypoxia; Insulin; Lactates; Liver; Male; Muscles; Pyruvate Kinase; Rats

Topics: Adenosine Triphosphate; Animals; Carbon Isotopes; Glucose; Glycogen; Glycolysis; Heart; Hypoxia; Lactates; Male; Myocardium; Norepinephrine; Perfusion; Phosphocreatine; Rats; Reserpine

Topics: Adaptation, Physiological; Altitude; Animals; Aortic Coarctation; Cerebral Cortex; Disease Models, Animal; Glycogen; Heart; Heart Failure; Hypoxia; Methods; Muscle Contraction; Myocardium; Phosphocreatine; Protein Biosynthesis; Rats; RNA

1. The ability of tricarboxylic acid-cycle metabolites to influence the physiological performance of the perfused anaerobic rat heart was investigated. Energy expenditure/h [(beats/min)x60xsystolic pressure/g of protein] for various anoxic conditions compared with oxygenated control hearts were: 5mm-glucose, 4.5%; 20mm- or 40mm-glucose, 10%; 20mm-glucose plus fumerate+malate+glutamate, 29%; 20mm-glucose plus oxaloacetate and alpha-oxoglutarate, 31%. 2. The energy expenditure/lactate production ratio was increased by the tricarboxylic acid-cycle metabolites, indicating that alterations in anaerobic physiological performance did not result from changes in glycolysis. 3. Analysis of tissue constituents provided further indication of an enhanced energy status for fumarate+malate+glutamate- and oxaloacetate+alpha-oxoglutarate-perfused hearts; tissue concentrations of both glycogen and ATP were higher than in the 20mm-glucose-perfused groups. 4. A marked increase in the accumulation of succinate in tissues perfused with oxaloacetate+alpha-oxoglutarate or fumarate+malate+glutamate provided further evidence that these metabolites were stimulating mitochondrial energy production under anoxia. 5. These studies indicate that mitochondrial ATP production can be stimulated in an isolated mammalian tissue perfused under anaerobiosis with a resulting enhancement of cell function.

Topics: Adenosine Triphosphate; Animals; Citric Acid Cycle; Fumarates; Glucose; Glutamates; Glycogen; Glycolysis; Heart; Heart Rate; Hypoxia; In Vitro Techniques; Ketoglutaric Acids; Lactates; Malates; Male; Metabolism; Myocardium; Oxaloacetates; Oxygen; Perfusion; Phosphocreatine; Rats; Succinates

Topics: Animals; Anthelmintics; Antimycin A; Carbohydrate Metabolism; Cyanides; Electron Transport; Electron Transport Complex IV; Glycogen; Glycolysis; Hypoxia; NAD; Oxygen; Oxygen Consumption; Rotenone; Sheep; Succinates; Thiazoles; Tissue Extracts; Trichostrongyloidea

Topics: Alkaline Phosphatase; Animals; Calcium; Cardiomyopathies; Digitoxin; Electron Transport Complex IV; Female; Glucosyltransferases; Glycogen; Histocytochemistry; Hypoxia; Lipid Metabolism; Necrosis; Oils; Papillary Muscles; Phosphates; Rats; Succinate Dehydrogenase; Water-Electrolyte Balance

Topics: Animals; Animals, Newborn; Asphyxia; Cats; Dogs; Female; Fetus; Glycogen; Glycolysis; Guinea Pigs; Haplorhini; Humans; Hydrogen-Ion Concentration; Hypoxia; Infant, Newborn; Lactates; Liver Glycogen; Myocardium; Pregnancy; Rabbits; Rats; Sheep

Topics: Animals; Cytoplasm; Disease Models, Animal; Glycogen; Hypoxia; Lipids; Liver; Liver Glycogen; Lysosomes; Microscopy, Electron; Rats

Topics: Acute Disease; Animals; Arrhythmias, Cardiac; Dogs; Glycogen; Histocytochemistry; Humans; Hydrogen; Hypoxia; Ischemia; Lactates; Mitochondria; Myocardial Infarction; Myocardium; Phosphates

Topics: Animals; Blood Glucose; Blood Proteins; Calcium; Cardiac Output; Chlorides; Female; Fetal Heart; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Lactates; Liver Glycogen; Maternal-Fetal Exchange; Muscles; Myocardium; Phosphates; Potassium; Pregnancy; Rabbits; Sodium; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Altitude; Citric Acid Cycle; Glycogen; Heart Diseases; Humans; Hypoxia; Ischemia; Lactates; Muscles; Oxidative Phosphorylation; Oxygen Consumption; Physical Exertion; Pyruvates

Topics: Animals; Brain; Brain Damage, Chronic; Brain Neoplasms; Carbohydrate Metabolism; Glucosephosphate Dehydrogenase; Glycogen; Hippocampus; Histocytochemistry; Humans; Hypothalamus; Hypoxia; Ischemia; Neurons; Nucleic Acids; Rats; Succinate Dehydrogenase; Transferases

1. The metabolic requirements for catecholamine secretion elicited by acetylcholine or by calcium plus high K(+) were studied on acutely denervated perfused cat adrenal glands.2. Glucose-deprivation plus anoxia caused an increase in the spontaneous catecholamine output from adrenal glands perfused with normal Locke solution, which was abolished by the removal of calcium from the perfusion medium.3. Anoxia plus glucose-deprivation did not depress the secretory response to repeated exposures of a low concentration of acetylcholine, but did depress the response to a higher concentration of acetylcholine. Glucose-deprivation and nitrogen, when imposed either separately or together, did not inhibit total catecholamine output in response to calcium. Differential analysis of the calcium-evoked secretion showed that during anoxia, catecholamine output was maintained primarily by adrenaline secretion.4. Cyanide (0.2 mM) potentiated the secretory response to calcium in the presence of glucose, but when glucose was omitted from the perfusion medium, cyanide caused a gradual decline in calcium-evoked secretion. Iodoacetic acid (IAA) (0.2 mM) depressed the response to calcium by about 50% under aerobic conditions and by 90% under anaerobic conditions.5. The glycogen content of medullae was profoundly depleted under anoxic conditions.6. It is concluded that energy is required for the secretory action of calcium on medullary chromaffin cells. The energy may be derived from glycolysis or oxidative metabolism. A possible interaction between calcium and adenosine triphosphate acid (ATP) in eliciting catecholamine secretion is discussed.7. The alteration in the percent adrenaline and noradrenaline secreted during anoxia indicates that anoxia may regulate medullary catecholamine secretion through a peripheral, as well as a central mechanism.

Topics: Acetylcholine; Adenosine Triphosphate; Adrenal Medulla; Animals; Calcium; Catecholamines; Cats; Chromaffin System; Cyanides; Denervation; Drug Synergism; Epinephrine; Glucose; Glycogen; Glycolysis; Hypoxia; Iodoacetates; Nitrogen; Norepinephrine; Perfusion; Potassium

Topics: Animals; Blood Pressure; Glucose; Glycogen; Heart Ventricles; Hypoxia; Insulin; Lipid Metabolism; Methods; Myocardium; Oxygen; Oxygen Consumption; Palmitic Acids; Rats; Tritium

Topics: Adenosine Triphosphate; Animals; Anura; Brain; Brain Chemistry; Fishes; Glucose; Glycogen; Hexokinase; Hydrogen-Ion Concentration; Hypoxia; Kinetics; Lactates; Mice; Oxygen Consumption; Phosphocreatine; Phosphofructokinase-1; Seasons; Turtles

Topics: Altitude; Animals; Blood Glucose; Brain; Caffeine; Glucose; Glycogen; Hypoxia; Lactates; Liver; Male; Myocardium; Rats

Topics: Animals; Catecholamines; Epinephrine; Glycogen; Heart; Heart Ventricles; Hypoxia; Isoproterenol; Male; Myocardium; Norepinephrine; Oxygen Consumption; Rats

Topics: Adrenal Glands; Adrenalectomy; Allantoin; Ammonia; Animals; Blood Glucose; Fasting; Fatty Acids, Nonesterified; Glycogen; Growth Hormone; Hydrocortisone; Hypophysectomy; Hypoxia; Lactates; Liver Glycogen; Male; Myocardium; Nitrogen; Oxygen Consumption; Phosphorus; Pituitary Gland; Rats; Stress, Physiological; Urea

Topics: Animals; Blood Chemical Analysis; Electrocardiography; Female; Fetal Heart; Glucose; Glycogen; Hypoxia; Infusions, Parenteral; Lactates; Liver Glycogen; Maternal-Fetal Exchange; Methods; Microscopy, Electron; Obstetric Labor Complications; Potassium; Pregnancy; Rabbits; Time Factors; Water

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Citrates; Glucose; Glycogen; Guinea Pigs; Heart Arrest, Induced; Hypothermia, Induced; Hypoxia; Lactates; Myocardium; Potassium; Temperature

Topics: Animals; Animals, Newborn; Bradycardia; Carbohydrate Metabolism; Dyspnea; Female; Glucose; Glycogen; Growth; Hypoxia; Liver; Liver Glycogen; Milk; Myocardium; Nutritional Physiological Phenomena; Rats

Topics: Acid-Base Equilibrium; Adenosine Triphosphate; Animals; Brain; Brain Edema; Carbon Dioxide; Electrolytes; Extracorporeal Circulation; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypothermia; Hypothermia, Induced; Hypoxia; Lactates; Male; Nucleosides; Partial Pressure; Phosphates; Phosphocreatine; Potassium; Pyruvates; Rats; Sodium; Water

Topics: Animals; Blood Circulation; Blood Glucose; Female; Fetal Heart; Glucose; Glycogen; Hydrogen-Ion Concentration; Hypoxia; Infusions, Parenteral; Liver; Maternal-Fetal Exchange; Pregnancy; Rabbits

Topics: Animals; Electrocardiography; Female; Glucose; Glycogen; Heart; Heart Rate; Histocytochemistry; Hyperglycemia; Hypoxia; Infusions, Parenteral; Myocardium; Pregnancy; Rabbits

Topics: Animals; Carbohydrate Metabolism; Glucosyltransferases; Glycogen; Histocytochemistry; Humans; Hypoxia; L-Lactate Dehydrogenase; Macrophages; Mice; Neutrophils; Phagocytosis; Polysaccharides

Topics: Adenosine Triphosphate; Adrenalectomy; Animals; Bradycardia; Catecholamines; Epinephrine; Glycogen; Hypertension; Hypoxia; Lactates; Methods; Myocardium; Nitrogen; Phosphocreatine; Rabbits; Statistics as Topic; Sympatholytics

Topics: Animals; Electric Stimulation; Ganglia, Autonomic; Glucagon; Glycogen; Hexoses; Histocytochemistry; Hydrocortisone; Hypoxia; Insulin; Microscopy, Electron; Neurons; Oxytocin; Rats; Vasopressins

Topics: Adenine Nucleotides; Animals; Animals, Newborn; Brain Chemistry; Environmental Exposure; Fetus; Freezing; Glycogen; Hypoxia; Lactates; Liver; Myocardium; Nitrogen; Phosphocreatine; Pyruvates; Rats

Topics: Animals; Asphyxia Neonatorum; Carbohydrates; Female; Fetal Death; Glycogen; Heart Arrest; Humans; Hyperkalemia; Hypoxia; Infant, Newborn; Myocardium; Pregnancy; Rabbits

Topics: Animals; Centrifugation; Cerebral Cortex; Chlorpromazine; Electric Stimulation; Electroshock; Freezing; Glucose; Glycogen; Hypoxia; Insulin; Lactates; Male; Mice; Pentylenetetrazole; Phenobarbital; Phosphocreatine; Secobarbital; Seizures; Stress, Physiological

Topics: Animals; Blood Glucose; Glycogen; Hypoxia; Liver; Muscles; Myocardium; Turtles

Topics: Adenosine Triphosphate; Animals; Citrates; Ethylenediamines; Fasting; Fatty Acids; Glycerophosphates; Glycogen; Hexosephosphates; Hypoxia; Injections, Intravenous; Lactates; Malates; Male; Myocardium; Pyruvates; Rats; Trioses

Topics: Animals; Glycogen; Histocytochemistry; Hypoxia; Myocardium; Phospholipids; Rats; Staining and Labeling

Topics: Animals; Electron Transport Complex IV; Glycogen; Hypoxia; Muscles; Oxygen Consumption; Phosphocreatine; Physical Exertion; Rats; Stimulation, Chemical; Swimming; Vitamin B Complex

Topics: Adenosine Triphosphate; Animals; Clinical Enzyme Tests; Cochlea; Glucose; Glycogen; Guinea Pigs; Histocytochemistry; Hypoxia; Ischemia; NAD; NADP; Organ of Corti; Phosphates; Phosphocreatine

Topics: Animals; Coronary Disease; Endoplasmic Reticulum; Glycogen; Hypoxia; Lipids; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Rats; Ribosomes

Topics: Amino Acids; Animals; Animals, Newborn; Blood Glucose; Glycogen; Hypoxia; Kidney; Lactates; Liver; Muscles; Myocardium; Pyruvates; Rabbits

Topics: Animals; Anura; Glycogen; Hypoxia; Liver Glycogen; Muscles; Myocardium

Topics: Animals; Blood; Cattle; Cell Membrane Permeability; Glycogen; Guinea Pigs; Hypoxia; In Vitro Techniques; Liver; Mononuclear Phagocyte System; Muscles; Myocardium; Potassium; Tissue Extracts

Topics: Altitude; Animals; Animals, Newborn; Brain; Glycogen; Hypoxia; Lactates; Rats

Topics: Blood Coagulation Disorders; Enzymes; Glycogen; Humans; Hypoxia; In Vitro Techniques

Topics: Acclimatization; Adult; Altitude; Blood Glucose; Epinephrine; Glycogen; Humans; Hypoxia; Lactates; Liver; Male; Phosphates; Potassium; Pyruvates

Topics: Animals; Dogs; Glucosyltransferases; Glycogen; Hypoxia; Lactates; Myocardium; Oxygen Consumption; Pyruvates; Shock, Hemorrhagic; Ventricular Function

Topics: Adenosine Triphosphate; Animals; Diaphragm; Dinitrophenols; Glucosyltransferases; Glycogen; Hexoses; Hypoxia; In Vitro Techniques; Muscles; Myocardium; Perfusion; Rats

Topics: Animals; Coronary Disease; Glycogen; Humans; Hypoxia; Lactates; Muscle, Smooth; Myocardium; Pyruvate Oxidase; Rats

Giant salamanders, Amphiuma means, measuring 240 to 280 millimeters from snout to vent, tolerate induced anoxia for 6 hours. After 3 hours of anoxia, hepatic glycogen units are reduced in size and concentration; after 6 hours the glycogen units are almost completely depleted. Greater development and changes in the density of the endoplasmic reticulum indicate that this structure participates in the mobilization of glycogen from the cell.

Topics: Animals; Endoplasmic Reticulum; Glycogen; Histocytochemistry; Hypoxia; Liver; Liver Glycogen; Research; Urodela

Topics: Carbohydrate Metabolism; Carbon Isotopes; Fasting; Fatty Acids; Glucose; Glycogen; Hypothermia; Hypothermia, Induced; Hypoxia; Lactates; Lipid Metabolism; Myocardium; Palmitates; Palmitic Acid; Radiometry; Rats; Temperature

Topics: Animals; Ganglia, Autonomic; Glycogen; Hypoxia; In Vitro Techniques; Liver; Liver Glycogen; Microscopy, Electron; Myocardium; Rats

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Axons; Carbohydrate Metabolism; Fructose; Glucose; Glycogen; Hypoxia; In Vitro Techniques; Ischemia; Lactates; Nerve Degeneration; Nervous System Diseases; Neurilemma; Oxygen Consumption; Peripheral Nerves; Phosphates; Phosphocreatine; Rabbits; Schwann Cells

Topics: Coronary Disease; Electron Transport Complex IV; Electrons; Fluorescence; Glycogen; Heart Diseases; Histocytochemistry; Humans; Hypoxia; Isoproterenol; Lipids; Microscopy; Microscopy, Electron; Microscopy, Fluorescence; Mitochondria; Myocardial Infarction; Myocardium; Necrosis; Pathology; Rats; Research; Succinate Dehydrogenase

Topics: Blood; Blood Glucose; Carbohydrate Metabolism; Central Nervous System; Glycogen; Hypoglycemia; Hypoxia; Lactates; Liver; Muscles; Nervous System; Physiology; Portal Vein; Pyruvates; Research; Shock

Topics: Animals; Animals, Newborn; Birth Weight; Brain; Carbohydrate Metabolism; Carbon Isotopes; Female; Fetal Death; Fetal Development; Glycogen; Glycolysis; Histocytochemistry; Hypoxia; Liver; Metabolism; Myocardium; Pregnancy; Pregnancy, Prolonged; Pyruvates; Rabbits; Research

Topics: Animals; Arabinose; Carbon Dioxide; Diabetes Mellitus, Experimental; Diaphragm; Fatty Acids; Glucose; Glycogen; Glycolysis; Heart; Hydroxybutyrates; Hypoxia; In Vitro Techniques; Muscles; Myocardium; Perfusion; Phosphofructokinase-1; Pyruvates; Rats; Salicylates; Starvation

Topics: Animals; Glycogen; Heart; Humans; Hypoxia; In Vitro Techniques; Metabolism; Mollusca; Myocardium; Octopodiformes

Topics: Animals; Carbohydrate Metabolism; Glucagon; Glycogen; Glycogenolysis; Hypoxia; Lactates; Lactic Acid; Muscles; Myocardium; Phosphorylases; Phosphotransferases; Rats

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Coenzymes; Glucose; Glycogen; Hypoxia; Lactates; Lung; Oxygen; Phosphorus; Phosphorus, Dietary; Rabbits; Research

Topics: Adenine Nucleotides; Animals; Carbohydrate Metabolism; Coenzymes; Glycogen; Heart; Heart Arrest; Heart Arrest, Induced; Hypoxia; Lactates; Metabolism; Myocardium; Phosphates; Pyruvates; Research; Vertebrates

Topics: Animals; Glycogen; Glycogenolysis; Heart; Hypoxia; Myocardium; Rats

Topics: Animals; Asphyxia; Fishes; Fresh Water; Glycogen; Hypercapnia; Hypoxia; Myocardium

Topics: Animals; Anura; Asphyxia; Glycogen; Glycogenolysis; Hypoxia; Muscles; Rana esculenta

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Carbohydrate Metabolism; Cardiovascular System; Fetus; Glycogen; Humans; Hypoxia; Infant, Newborn; Sheep

Topics: Fishes; Fresh Water; Glycogen; Glycogenolysis; Heart; Hypoxia; Myocardium

Topics: Animal Structures; Animals; Carbohydrate Metabolism; Glucose; Glycogen; Glycogenolysis; Hypoxia; Lactates

Topics: Animals; Glycogen; Glycogenolysis; Hypoxia; Muscle Contraction; Myocardium; Rats

Topics: Anesthesia; Brain; Glycogen; Glycogenolysis; Hypoxia; Neurochemistry

Topics: Dehydration; Female; Glycogen; Glycogenolysis; Heart; Humans; Hypoxia; Muscle, Skeletal; Muscles; Myocardium; Shock; Uterus

Topics: Animals; Anura; Asphyxia; Glycogen; Hypoxia; Muscles; Rana esculenta; Ranidae

Topics: Adenosine Triphosphate; Dehydration; Glycogen; Hypoxia; Muscles; Musculoskeletal Physiological Phenomena

Topics: Animals; Glycogen; Glycogenolysis; Hypoxia; Lagomorpha; Rabbits

Topics: Adenosine Triphosphate; Dehydration; Female; Glycogen; Glycogenolysis; Heart; Humans; Hypoxia; Muscles; Myocardium; Shock; Uterus

Topics: Animals; Anura; Asphyxia; Glycogen; Hypoxia; Liver; Liver Glycogen; Rana esculenta; Ranidae

Topics: Animals; Glycogen; Glycogenolysis; Heart; Hypoxia; Myocardium

Topics: Carbon Dioxide; Carbonic Acid; Glycogen; Heart; Hypoxia; Mercury; Myocardium; Organogenesis

Topics: Glycogen; Glycogenolysis; Heart; Humans; Hypoxia; Myocardium

Topics: Glycogen; Glycogenolysis; Heart; Hypoxia; Myocardium

Topics: Glycogen; Glycogenolysis; Humans; Hypoxia; Liver; Oxygen

Topics: Anhydrides; Asphyxia; Carbon; Carbon Dioxide; Glycogen; Glycogenolysis; Heart; Hypoxia; Myocardium

Topics: Animals; Burns; Glycogen; Heart; Histamine; Histamine Agents; Hypoxia; Myocardium; Rats

Topics: Glycogen; Glycogenolysis; Heart; Humans; Hypoxia; Myocardium

Topics: Air Pollutants; Asphyxia; Carbon Dioxide; Glycogen; Heart; Hypoxia

Topics: Glycogen; Humans; Hypoxia; Liver Glycogen

Topics: Glycogen; Heart; Humans; Hypoxia; Myocardium

Topics: Carbon Dioxide; Fasting; Glycogen; Hypoxia; Oxygen

Topics: Carbon Dioxide; Glycogen; Hypoxia; Liver; Liver Glycogen; Muscles; Oxygen; Stomach