glycogen and Ischemia

Topics: Adenosine Triphosphate; Animals; Biological Transport, Active; Cyclic AMP; Ear, Inner; Energy Metabolism; Glycogen; Guinea Pigs; Humans; Ischemia; Membrane Potentials; Potassium; Rats; Sodium

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: Animals; Autolysis; Calcium; Calcium Radioisotopes; Coronary Vessels; Glycogen; Ischemia; Mitochondria, Muscle; Mitochondrial Swelling; Myocardium; Myofibrils; Papillary Muscles; Perfusion; Sarcoplasmic Reticulum; Time Factors

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

Topics: Adaptation, Physiological; Animals; Dogs; Glycogen; Glycolysis; Guinea Pigs; Heart; Humans; Ischemia; Macromolecular Substances; Mitochondria, Muscle; Myocardial Infarction; Myocardium; Oxygen Consumption; Rats

1. In ischaemic exercise ATP is supplied only by glycogenolysis and net splitting of phosphocreatine (PCr). Furthermore, 'proton balance' involves only glycolytic lactate/H+ generation and net H+ 'consumption' by PCr splitting. This work examines the interplay between these, metabolic regulation and the creatine kinase equilibrium. 2. Nine male subjects (age 25-45 years) performed finger flexion (7 % maximal voluntary contraction at 0.67 Hz) under cuff ischaemia. 31P magnetic resonance spectra were acquired from finger flexor muscle in a 4.7 T magnet using a 5 cm surface coil. 3. Initial PCr depletion rate estimates total ATP turnover rate; glycolytic ATP synthesis was obtained from this and changes in [PCr], and then used to obtain flux through 'distal' glycolysis (phosphofructokinase and beyond) to lactate; 'proximal' flux (through phosphorylase) was obtained from this and changes in [phosphomonoester]. Total H+ load (lactate load less H+ consumption) was used to estimate cytosolic buffer capacity (beta). 4. Glycolytic ATP synthesis increased from near zero while PCr splitting declined. Net H+ load was approximately linear with pH, suggesting beta = 20 mmol x l(-1) (pH unit)(-1) at rest, increasing as pH falls. 5. Relationships between glycolytic rate and changes in [PCr] (i.e. the time-integrated mismatch between ATP use and production), and thus also [P(i)] (substrate for phosphorylase), suggest that increase in glycolysis is due partly to 'open-loop' Ca2+-dependent conversion of phosphorylase b to a, and partly to the 'closed loop' increase in P(i) consequent on net PCr splitting. 6. The 'settings' of these mechanisms have a strong influence on changes in pH and metabolite concentrations.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adult; Algorithms; Cytosol; Exercise; Glycogen; Glycolysis; Humans; Hydrogen-Ion Concentration; Ischemia; Kinetics; Lactates; Magnetic Resonance Spectroscopy; Male; Middle Aged; Muscle, Skeletal; Phosphocreatine; Phosphofructokinases; Protons

Neural activity is costly and requires continuous ATP from aerobic metabolism. Brainstem motor function of American bullfrogs normally collapses after minutes of ischaemia, but following hibernation, it becomes ischaemia-tolerant, generating output for up to 2 h without oxygen or glucose delivery. Transforming the brainstem to function during ischaemia involves a switch to anaerobic glycolysis and brain glycogen. We hypothesized that improving neural performance during ischaemia involves a transcriptional program for glycogen and glucose metabolism. Here we measured mRNA copy number of genes along the path from glycogen metabolism to lactate production using real-time quantitative PCR. The expression of individual genes did not reflect enhanced glucose metabolism. However, the number of co-expressed gene pairs increased early into hibernation, and by the end, most genes involved in glycogen metabolism, glucose transport and glycolysis exhibited striking linear co-expression. By contrast, co-expression of genes in the Krebs cycle and electron transport chain decreased throughout hibernation. Our results uncover reorganization of the metabolic transcriptional network associated with a shift to ischaemia tolerance in brain function. We conclude that modifying gene co-expression may be a critical step in synchronizing storage and use of glucose to achieve ischaemia tolerance in active neural circuits.

Topics: Brain; Glucose; Glycogen; Glycolysis; Humans; Ischemia; RNA, Messenger

Hypoxia-inducible factor (HIF) mediates protection via hypoxic preconditioning in both, in vitro and in vivo ischemia models. However, the underlying mechanism remains largely unknown. Prolyl hydroxylase domain proteins serve as the main HIF regulator via hydroxylation of HIFα leading to its degradation. At present, prolyl hydroxylase inhibitors including enarodustat are under clinical trials for the treatment of renal anemia. In an in vitro model of ischemia produced by oxygen-glucose deprivation of renal proximal tubule cells in culture, enarodustat treatment and siRNA knockdown of prolyl hydroxylase 2, but not of prolyl hydroxylase 1 or prolyl hydroxylase 3, significantly increased the cell viability and reduced the levels of reactive oxygen species. These effects were offset by the simultaneous knockdown of HIF1α. In another in vitro ischemia model induced by the blockade of oxidative phosphorylation with rotenone/antimycin A, enarodustat-enhanced glycogen storage prolonged glycolysis and delayed ATP depletion. Although autophagy is another possible mechanism of prolyl hydroxylase inhibition-induced cytoprotection, gene knockout of a key autophagy associated protein, Atg5, did not affect the protection. Enarodustat increased the expression of several enzymes involved in glycogen synthesis, including phosphoglucomutase 1, glycogen synthase 1, and 1,4-α glucan branching enzyme. Increased glycogen served as substrate for ATP and NADP production and augmented reduction of glutathione. Inhibition of glycogen synthase 1 and glutathione reductase nullified enarodustat's protective effect. Enarodustat also protected the kidneys in a rat ischemia reperfusion injury model and the protection was partially abrogated by inhibiting glycogenolysis. Thus, prolyl hydroxylase inhibition protects the kidney from ischemia via upregulation of glycogen synthesis.

Topics: Animals; Glycogen; Hypoxia-Inducible Factor 1, alpha Subunit; Ischemia; Kidney; N-substituted Glycines; Prolyl Hydroxylases; Pyridines; Rats; Triazoles; Up-Regulation

Increasing evidence indicates that pericytes are vulnerable cells, playing pathophysiological roles in various neurodegenerative processes. Microvascular pericytes contract during cerebral and coronary ischemia and do not relax after re-opening of the occluded artery, causing incomplete reperfusion. However, the cellular mechanisms underlying ischemia-induced pericyte contraction, its delayed emergence, and whether it is pharmacologically reversible are unclear. Here, we investigate i) whether ischemia-induced pericyte contractions are mediated by alpha-smooth muscle actin (α-SMA), ii) the sources of calcium rise in ischemic pericytes, and iii) if peri-microvascular glycogen can support pericyte metabolism during ischemia. Thus, we examined pericyte contractility in response to retinal ischemia both in vivo, using adaptive optics scanning light ophthalmoscopy and, ex vivo, using an unbiased stereological approach. We found that microvascular constrictions were associated with increased calcium in pericytes as detected by a genetically encoded calcium indicator (NG2-GCaMP6) or a fluoroprobe (Fluo-4). Knocking down α-SMA expression with RNA interference or fixing F-actin with phalloidin or calcium antagonist amlodipine prevented constrictions, suggesting that constrictions resulted from calcium- and α-SMA-mediated pericyte contractions. Carbenoxolone or a Cx43-selective peptide blocker also reduced calcium rise, consistent with involvement of gap junction-mediated mechanisms in addition to voltage-gated calcium channels. Pericyte calcium increase and capillary constrictions became significant after 1 h of ischemia and were coincident with depletion of peri-microvascular glycogen, suggesting that glucose derived from glycogen granules could support pericyte metabolism and delay ischemia-induced microvascular dysfunction. Indeed, capillary constrictions emerged earlier when glycogen breakdown was pharmacologically inhibited. Constrictions persisted despite recanalization but were reversible with pericyte-relaxant adenosine administered during recanalization. Our study demonstrates that retinal ischemia, a common cause of blindness, induces α-SMA- and calcium-mediated persistent pericyte contraction, which can be delayed by glucose driven from peri-microvascular glycogen. These findings clarify the contractile nature of capillary pericytes and identify a novel metabolic collaboration between peri-microvascular end-feet and pericytes.

Topics: Actins; Animals; Capillaries; Glycogen; Ischemia; Mice; Mice, Transgenic; Ophthalmoscopy; Pericytes; Retina; Retinal Diseases; Retinal Vessels; Vasoconstriction

Pyruvate is a key intermediary in energy metabolism and can exert antioxidant and anti-inflammatory effects. However, the fate of pyruvate during AKI remains unknown. Here, we assessed renal cortical pyruvate and its major determinants (glycolysis, gluconeogenesis, pyruvate dehydrogenase [PDH], and H2O2 levels) in mice subjected to unilateral ischemia (15-60 minutes; 0-18 hours of vascular reflow) or glycerol-induced ARF. The fate of postischemic lactate, which can be converted back to pyruvate by lactate dehydrogenase, was also addressed. Ischemia and glycerol each induced persistent pyruvate depletion. During ischemia, decreasing pyruvate levels correlated with increasing lactate levels. During early reperfusion, pyruvate levels remained depressed, but lactate levels fell below control levels, likely as a result of rapid renal lactate efflux. During late reperfusion and glycerol-induced AKI, pyruvate depletion corresponded with increased gluconeogenesis (pyruvate consumption). This finding was underscored by observations that pyruvate injection increased renal cortical glucose content in AKI but not normal kidneys. AKI decreased PDH levels, potentially limiting pyruvate to acetyl CoA conversion. Notably, pyruvate therapy mitigated the severity of AKI. This renoprotection corresponded with increases in cytoprotective heme oxygenase 1 and IL-10 mRNAs, selective reductions in proinflammatory mRNAs (e.g., MCP-1 and TNF-α), and improved tissue ATP levels. Paradoxically, pyruvate increased cortical H2O2 levels. We conclude that AKI induces a profound and persistent depletion of renal cortical pyruvate, which may induce additional injury.

Topics: Acute Kidney Injury; Adenosine Triphosphate; Animals; Gluconeogenesis; Glucose; Glycogen; Hydrogen Peroxide; Ischemia; Kidney Cortex; Kidney Tubules; Lactic Acid; Male; Mice; Pyruvate Dehydrogenase Complex; Pyruvic Acid; Reperfusion Injury

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

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

To examine metabolism during exercise in 2 patients with muscle phosphorylase kinase (PHK) deficiency and to further define the phenotype of this rare glycogen storage disease (GSD).. Patient 1 (39 years old) had mild exercise-induced forearm pain, and EMG showed a myopathic pattern. Patient 2 (69 years old) had raised levels of creatine kinase (CK) for more than 6 months after statin treatment. Both patients had increased glycogen levels in muscle and PHK activity <11% of normal. Two novel pathogenic nonsense mutations were found in the PHKA1 gene. The metabolic response to anaerobic forearm exercise and aerobic cycle exercise was studied in the patients and 5 healthy subjects.. Ischemic exercise showed a normal 5-fold increase in plasma lactate (peak 5.7 and 6.9 mmol/L) but an exaggerated 5-fold increase in ammonia (peak 197 and 171 μmol/L; control peak range 60-113 μmol/L). An incremental exercise test to exhaustion revealed a blunted lactate response (5.4 and 4.8 mmol/L) vs that for control subjects (9.6 mmol/L; range 7.1-14.3 mmol/L). Fat and carbohydrate oxidation rates at 70% of peak oxygen consumption were normal. None of the patients developed a second wind phenomenon or improved their work capacity with an IV glucose infusion.. Our findings demonstrate that muscle PHK deficiency may present as an almost asymptomatic condition, despite a mild impairment of muscle glycogenolysis, raised CK levels, and glycogen accumulation in muscle. The relative preservation of glycogenolysis is probably explained by an alternative activation of myophosphorylase by AMP and P(i) at high exercise intensities.

Topics: Adult; Aged; Ammonia; Biopsy; Carbohydrate Metabolism; Creatine Kinase; Exercise; Exercise Test; Forearm; Genetic Variation; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type V; Glycogenolysis; Humans; Ischemia; Lactates; Lipid Metabolism; Male; Muscle, Skeletal; Oxygen Consumption; Pain; Phenotype; Phosphorylase Kinase; Regional Blood Flow

In children with congenital heart disease, female sex has been linked to greater in-hospital mortality associated with low cardiac output, yet the reasons for this are unclear. Therefore, we examined whether newborn sex differences in the heart's metabolic response to ischemia exist. Left ventricular (LV) in vivo and ischemic biopsies of newborn male and female piglets were compared. Tissue ATP, creatine phosphate (CP), glycogen, anaerobic end-products lactate and hydrogen ion (H), and key regulatory enzymes were measured. Compared with males, newborn females displayed 14% lower ATP, 22% lower CP, and 32% lower glycogen reserves (p < 0.05) at baseline. During ischemia, newborn females accumulated 17% greater lactate and 40% greater H accumulation (p < 0.02), which was associated with earlier cessation of glycolysis and lower ischemic ATP levels (p < 0.02) compared with males. Newborn females demonstrated a greater ability to use their glycogen reserves, resulting in significantly lower (p < 0.003) glycogen levels throughout the ischemic period. Thus, newborn females are at a metabolic disadvantage because they exhibited lower energy levels and greater tissue lactic acidosis, both linked to an increase susceptibility to ischemic injury and impair myocardial function on reperfusion.

Topics: Adenosine Triphosphate; Analysis of Variance; Animals; Animals, Newborn; Energy Metabolism; Female; Fluorometry; Glycogen; Heart Ventricles; Ischemia; Lactic Acid; Male; Myocardium; Phosphocreatine; Protons; Sex Factors; Sus scrofa

Skeletal muscle can maintain ATP concentration constant during the transition from rest to exercise, whereas metabolic reaction rates may increase substantially. Among the key regulatory factors of skeletal muscle energy metabolism during exercise, the dynamics of cytosolic and mitochondrial NADH and NAD+ have not been characterized. To quantify these regulatory factors, we have developed a physiologically based computational model of skeletal muscle energy metabolism. This model integrates transport and reaction fluxes in distinct capillary, cytosolic, and mitochondrial domains and investigates the roles of mitochondrial NADH/NAD+ transport (shuttling) activity and muscle glycogen concentration (stores) during moderate intensity exercise (60% maximal O2 consumption). The underlying hypothesis is that the cytosolic redox state (NADH/NAD+) is much more sensitive to a metabolic disturbance in contracting skeletal muscle than the mitochondrial redox state. This hypothesis was tested by simulating the dynamic metabolic responses of skeletal muscle to exercise while altering the transport rate of reducing equivalents (NADH and NAD+) between cytosol and mitochondria and muscle glycogen stores. Simulations with optimal parameter estimates showed good agreement with the available experimental data from muscle biopsies in human subjects. Compared with these simulations, a 20% increase (or approximately 20% decrease) in mitochondrial NADH/NAD+ shuttling activity led to an approximately 70% decrease (or approximately 3-fold increase) in cytosolic redox state and an approximately 35% decrease (or approximately 25% increase) in muscle lactate level. Doubling (or halving) muscle glycogen concentration resulted in an approximately 50% increase (or approximately 35% decrease) in cytosolic redox state and an approximately 30% increase (or approximately 25% decrease) in muscle lactate concentration. In both cases, changes in mitochondrial redox state were minimal. In conclusion, the model simulations of exercise response are consistent with the hypothesis that mitochondrial NADH/NAD+ shuttling activity and muscle glycogen stores affect primarily the cytosolic redox state. Furthermore, muscle lactate production is regulated primarily by the cytosolic redox state.

Topics: Biological Transport; Computer Simulation; Cytosol; Energy Metabolism; Exercise; Glycogen; Humans; Ischemia; Kinetics; Lactic Acid; Mitochondria, Muscle; Models, Biological; Muscle, Skeletal; NAD; Oxidation-Reduction; Oxygen Consumption; Recovery of Function; Regional Blood Flow; Reproducibility of Results

To determine if detrusor glycogen content in a bladder after removal of a urethral obstruction reflects the situation of bladder dysfunction as it existed during the period of obstruction.. The glycogen content of the detrusor was scored using a Periodic Acid Schiff's (PAS) staining. It was related to the functional history of the bladder. Bladder tissue was obtained from a guinea-pig model for posterior urethral valves where animals had been obstructed for up to 10 weeks, de-obstructed and allowed to recover for 2--8 weeks. Bladder urodynamic function had been documented with multiple measurements for the complete period of obstruction and de-obstruction.. The degree of glycogen deposition in a bladder after de-obstruction correlated directly with bladder function during obstruction. The strongest glycogen deposition was found in bladders having experienced the highest pressures, most instabilities, lowest compliance and highest contractility. In contrast, the bladder glycogen content was not related to the function of the bladder at the day the tissue was obtained, except for a relation between high glycogen content and continuing low compliance.. The glycogen content of a bladder reflects the history of bladder dysfunction, also when measured during a recovery period. This window on the functional history of a bladder may be of clinical value for picking out potential bad-responders to therapy in patients with incomplete data on bladder function during a previous period of bladder obstruction.

Topics: Animals; Glycogen; Guinea Pigs; In Vitro Techniques; Ischemia; Muscle, Smooth; Periodic Acid-Schiff Reaction; Urethra; Urinary Bladder; Urinary Bladder Neck Obstruction; Urodynamics

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 great resistance of muscle to ischemia was used to study blood flow-dependent phenomena produced by anesthetic drugs in this condition. A short reperfusion period was used in order to favor metabolic changes indicative of an effect of chlorpromazine (CPZ) on blood flow. Gracilis muscles of dogs were submitted to 5 h of ischemia and 30 min of reperfusion. CPZ-treated animals were injected I.V. (2 mg/kg) 10 min before the beginning of ischemia. Biopsies provided the material for tissue measurements. Lactate content and pH were determined in blood samples collected from a muscle efferent vein. In both the CPZ-treated and nontreated groups, ischemia induced a decline in muscle glycogen content, with a corresponding increase in muscle lactate and a decrease in mitochondrial respiratory control ratio. After 30 min of reperfusion, tissue levels of lactate did not attain preischemic values but showed a clear decline in the two experimental groups, evidencing the reversible state of the muscle. All other metabolic parameters remained unchanged. Mitochondrial respiratory control remained functional during ischemia and reperfusion. Blood pH displayed similar changes in both groups. There was no metabolic indication that the drug affected blood flow during early reperfusion and/or of a greater sensitivity of muscle endothelial cells to anesthetic drugs.

Topics: Animals; Chlorpromazine; Disease Models, Animal; Dogs; Glycogen; Hydrogen-Ion Concentration; Ischemia; Lactates; Mitochondria, Muscle; Muscle Contraction; Muscle, Skeletal; Musculoskeletal Physiological Phenomena; Reference Values; Reperfusion Injury

The purpose of this study was to determine if elevated myocardial glycogen content could obviate Ca(2+) overload and subsequent myocardial injury in the setting of low oxygen and diminished exogenous substrate supplies. Isolated harp seal cardiomyocytes, recognized as having large glycogen stores, were incubated under conditions simulating ischemia (oxygen and substrate deprivation) for 1 h. Rat cardiomyocytes were used for comparison. Freshly isolated seal cardiomyocytes contained approximately 10 times more glycogen than those from rats (479 +/- 39 vs. 48 +/- 5 nmol glucose/mg dry weight (dry wt), mean +/- S.E., n = 6), and during ischemia lactate production was significantly greater in seal compared to rat cardiomyocytes (660 +/- 99 vs. 97 +/- 14 nmol/mg dry wt), while glycogen content decreased both in seal (from 479 +/- 39 to 315 +/- 58 nmol glucose/mg dry wt) and rat cardiomyocytes (from 48 +/- 5 to 18 +/- 5 nmol glucose/mg dry wt). Cellular ATP was well maintained in ischemic seal cardiomyocytes, whereas it showed a 65% decline (from 31 +/- 3 to 11 +/- 1 nmol ATP/mg dry wt) in rat cardiomyocytes. Similarly, total seal cardiomyocyte Ca(2+) content was not affected by ischemia, while Ca(2+) increased from 8.5 +/- 2.0 to 13.3 +/- 2.0 nmol/mg dry wt in ischemic rat myocytes. Rat cardiomyocytes also showed a notable decline in the percentage of rod-shaped cells in response to ischemia (from 66 +/- 4% to 30 +/- 3%), and cell morphology was unaffected in seal incubations. Addition of iodoacetate (IAA, an inhibitor of glycolysis) to seal cardiomyocytes, on top of substrate and oxygen deprivation, reduced the cellular content of ATP by 52.9 +/- 4.4% (from 25 +/- 4 to 11 +/- 2 nmol ATP/mg dry wt) and the percentage of rod-shaped myocytes from 51 +/- 3% to 28 +/- 4%, while total Ca(2+) content was unchanged by these conditions. Seal cardiomyocytes thus tolerate low oxygen conditions better than rat cardiomyocytes. This finding is most likely due to a higher glycolysis rate in seals, fueled by larger myocardial glycogen stores.

Topics: Adenosine Triphosphate; Animals; Calcium; Cells, Cultured; Glucose; Glycogen; Glycolysis; Ischemia; Lactic Acid; Microscopy, Electron; Myocytes, Cardiac; Oxygen; Rats; Rats, Sprague-Dawley; Seals, Earless; Species Specificity

To find a prognosis model of human liver transplant, we evaluate 62 surgical biopsies for the loss of glycogen and its variations in relation to cold ischemia, reperfusion, lobular zonation and donor's ages. We applied univariate, multivariate and discriminant analysis and logistic regression. There was a clear lobular zonation of glycogen during cold ischemia and at reperfusion. During cold ischemia, the mean loss was 48% in periportal zones and 74% in pericentrilobular zones. At reperfusion, it was in the range of 60% in periportal zones and 95% in pericentrilobular zones. It was observed in 64% of the grafts for an ischemia time less than 10 hr and in 82% of the grafts for an ischemia time of 10 hr or more. It was increased by 90% at reperfusion with pericentral predominance. Donors' age was an aggravating factor of glycogen loss beyond 28 years of age. In conclusion, in periportal zones, mean global glycogen depletion was about 54% during cold ischemia and reperfusion. It decreased by 90% at reperfusion with pericentral predominance. Logistic regression has allowed modelization of cold ischemia and reperfusion.

Topics: Adolescent; Adult; Child; Glycogen; Humans; Immunohistochemistry; Ischemia; Liver; Liver Transplantation; Middle Aged; Multivariate Analysis; Reperfusion

In this study, we investigated the hypothesis that prolonged ischemia would impair both sarcoplasmic reticulum (SR) Ca(2+) uptake and Ca(2+) release in skeletal muscle. To induce total ischemia (I), a tourniquet was placed around the upper hindlimb in 30 female Sprague-Dawley rats [wt = 256 +/- 6.7 (SE) g] and inflated to 350 mmHg for 4 h. The contralateral limb served as control (C). Immediately after the 4 h of ischemia, mixed gastrocnemius and tibialis anterior muscle was sampled from both limbs, and both crude muscle homogenates and SR vesicles were prepared. In another 10 control animals (CC), muscles were sampled and prepared exactly the same way, but immediately after anesthetization. Ca(2+) uptake and Ca(2+) release were measured in vitro with Indo-I on both homogenates and SR vesicles. As hypothesized, submaximal Ca(2+) uptake was lower (P < 0.05) in I compared with CC and C, by 25 and 45% in homogenates and SR vesicles, respectively. Silver nitrate (AgNO(3))-induced Ca(2+) release, which occurred in two phases (phase 1 and phase 2), was also altered in I compared with CC and C, in both muscle homogenates and SR vesicles. With ischemia, phase 1 peak Ca(2+) release was 26% lower (P < 0.05) in SR vesicles only. For phase 2, peak Ca(2+) release was 54 and 24% lower (P < 0.05) in SR vesicles and homogenates, respectively. These results demonstrate that prolonged skeletal muscle ischemia leads to a reduced SR Ca(2+) uptake in both homogenates and SR vesicles. The effects of ischemia on SR Ca(2+) release, however, depend on both the phase examined and the type of tissue preparation.

Topics: Adenosine Triphosphate; Animals; Calcium; Creatine; Enzyme Inhibitors; Female; Fluorescent Dyes; Glycogen; Hindlimb; Indoles; Ischemia; Lactic Acid; Muscle Contraction; Muscle, Skeletal; Oxalic Acid; Phosphates; Phosphocreatine; Rats; Rats, Sprague-Dawley; Ryanodine; Sarcoplasmic Reticulum; Silver Nitrate

N-methyl-1-deoxynojirimycin (NMDN), an a-glucosidase inhibitor, reduces myocardial infarct size by reducing the glycogenolytic rate through inhibition of the alpha-1,6-glucosidase of glycogen-debranching enzyme in the heart, in addition to possessing an antihyperglycemic action by blocking alpha-1,4-glucosidase in the intestine. Ischemic preconditioning (PC), which markedly reduces the size of the myocardial infarct, is known to reduce the activity of phosphorylase and reduce the glycogenolytic rate. Therefore, it was hypothesized that a combination of pharmacological inhibition of glycogenolysis by an alpha-1,6-glucosidase inhibitor, NMDN, and PC could markedly reduce myocardial infarct size more than NMDN or PC alone. Japanese white rabbits without collateral circulation were subjected to a 30-min coronary occlusion followed by 48-h reperfusion. The infarct sizes as a percentage of area at risk were significantly reduced by pre-ischemic treatment with either 100mg/kg of NMDN or PC of 5 min ischemia and 5 min reperfusion alone (15.9+/-2.0%, n=8, and 10.3+/-1.2%, n=8, respectively) as compared with the control (43.9+/-2.2%, n=8). However, the combination of 100mg/kg of NMDN and PC significantly reduced the infarct size (4.9+/-1.2, n=8) compared with NMDN or PC alone. Another 40 rabbits, also given 100mg of NMDN, PC, NMDN+PC or saline before ischemia (n=10 in each group), were killed for biochemical analysis after 30 min of ischemia. NMDN and PC preserved the glycogen content and attenuated the lactate accumulation, respectively, as compared with the control. However, the combination of NMDN and PC preserved significantly more glycogen and significantly reduced lactate accumulation than either NMDN or PC alone. The combination of NMDN and PC markedly reduced the myocardial infarct size more than either process alone. The marked preservation of glycogen and marked attenuation of lactate accumulation by the combination of NMDN and PC suggest that the mechanism for this effect of NMDN+PC is related to the inhibition of glycogenolysis.

Topics: 1-Deoxynojirimycin; Animals; Combined Modality Therapy; Disease Models, Animal; Enzyme Inhibitors; Glycogen; Glycoside Hydrolase Inhibitors; Heart Ventricles; Ischemia; Ischemic Preconditioning, Myocardial; Lactic Acid; Myocardial Infarction; Rabbits

To investigate the hypothesis that ischemia and reperfusion would impair sarcoplasmic reticulum (SR) Ca(2+) regulation in skeletal muscle, Sprague-Dawley rats (n = 20) weighing 290 +/- 3.5 g were randomly assigned to either a control control (CC) group, in which only the effects of anesthetization were studied, or to a group in which the muscles in one hindlimb were made ischemic for 4 h and allowed to recover for 1 h (I). The nonischemic, contralateral muscles served as control (C). Measurements of Ca(2+)-ATPase properties in homogenates and SR vesicles, in mixed gastrocnemius and tibialis anterior muscles, indicated no differences between groups on maximal activity, the Hill coefficient, and Ca(50), defined as the Ca(2+) concentration needed to elicit 50% of maximal activity. In homogenates, Ca(2+) uptake was lower (P < 0.05) by 20-25%, measured at 0.5 and 1.0 microM of free Ca(2+) ([Ca(2+)](f)) in C compared with CC. In SR vesicles, Ca(2+) uptake was lower (P < 0.05) by 30-38% in I compared with CC at [Ca(2+)](f) between 0.5 and 1.5 microM. Silver nitrate induced Ca(2+) release, assessed during both the initial, early rapid (phase 1), and slower, prolonged late (phase 2) phases, in homogenates and SR vesicles, indicated a higher (P < 0.05) release only in phase 1 in SR vesicles in I compared with CC. These results indicate that the alterations in SR Ca(2+) regulation, previously observed after prolonged ischemia by our group, are reversed within 1 h of reperfusion. However, the lower Ca(2+) uptake observed in long-term, nonischemic homogenates suggests that altered regulation may occur in the absence of ischemia.

Topics: Animals; Biological Transport; Calcium; Calcium-Transporting ATPases; Creatine; Female; Glycogen; Hindlimb; Ischemia; Kinetics; Lactates; Muscle Contraction; Muscle, Skeletal; Phosphates; Phosphocreatine; Rats; Rats, Sprague-Dawley; Reference Values; Reperfusion; Sarcoplasmic Reticulum; Time Factors

We evaluated the possibility that ischemic preconditioning could modify hepatic energy metabolism during ischemia. Accordingly, high-energy nucleotides and their degradation products, glycogen and glycolytic intermediates and regulatory metabolites, were compared between preconditioned and nonpreconditioned livers. Preconditioning preserved to a greater extent ATP, adenine nucleotide pool, and adenylate energy charge; the accumulation of adenine nucleosides and bases was much lower in preconditioned livers, thus reflecting slower adenine nucleotide degradation. These effects were associated with a decrease in glycogen depletion and reduced accumulation of hexose 6-phosphates and lactate. 6-Phosphofructo-2-kinase decreased in both groups, reducing the availability of fructose-2, 6-bisphosphate. Preconditioning sustained metabolite concentration at higher levels although this was not correlated with an increased glycolytic rate, suggesting that adenine nucleotides and cAMP may play the main role in the modulation of glycolytic pathway. Preconditioning attenuated the rise in cAMP and limited the accumulation of hexose 6-phosphates and lactate, probably by reducing glycogen depletion. Our results suggest the induction of metabolic arrest and/or associated metabolic downregulation as energetic cost-saving mechanisms that could be induced by preconditioning.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Cyclic AMP; Energy Metabolism; Fructosediphosphates; Fructosephosphates; Glucose-6-Phosphate; Glycogen; Glycolysis; Ischemia; Ischemic Preconditioning; Lactic Acid; Liver; Male; Phosphofructokinase-2; Phosphotransferases (Alcohol Group Acceptor); Rats

This study was designed to determine changes in myocardial contractile function and fuel selection during moderate coronary hypoperfusion in the presence of elevated plasma free fatty acid (FFA) at normal and reduced blood glucose concentrations. Coronary perfusion pressure (CPP) was sequentially lowered from 100 to 60, 50, and 40 mmHg in the left anterior descending coronary artery (LAD) of anesthetized, open-chest dogs. Regional glucose uptake (GU), fatty acid uptake (FAU), percentage segment shortening (%SS), and oxygen consumption (MV O(2)) were determined with normal arterial plasma FFA concentrations (Group 1) or with elevated FFA concentrations (Groups 2 and 3). In Group 3, glucose in the coronary perfusate blood was reduced from 3.53+/-0.36 to 0.15+/-0.03 m M by hemodialysis. In Group 1, FAU fell by 85% as CPP was lowered to 60 mmHg and remained depressed as CPP was reduced further; GU did not fall significantly. Hyperlipidemia in Group 2 did not alter GU at any CPP, but maintained FAU at baseline levels until CPP was lowered to 40 mmHg. At 40 mmHg CPP, myocardial function and metabolic variables were similar in Groups 1 and 2. In Group 3 at 40 mmHg, FAU increased four-fold and MV O(2)doubled v Groups 1 and 2, and GU fell to zero. Despite these metabolic changes, %SS in Group 3 was unchanged relative to Group 2. Addition of glucose to the dialysate prevented the effects of dialysis on FAU, GU, and MV O(2). Thus, preferential glucose oxidation sustains myocardial oxygen utilization efficiency [(heart rate x %SS x maximum left ventricular pressure)/MV O(2)] during hypoperfusion. Blocking preferential glucose oxidation by combined hyperlipidemia and hypoglycemia lowers oxygen utilization efficiency, but does not compromise myocardial contractile function.

Topics: Animals; Blood Glucose; Dogs; Fatty Acids; Female; Glucose; Glycogen; Hemodynamics; Hyperlipidemias; Hypoglycemia; Ischemia; Lactic Acid; Male; Myocardial Contraction; Myocardium; Oxygen; Oxygen Consumption; Perfusion; Pressure

The aim of this study was to provide in vivo experimental evidence for the proposed biological significance of the creatine kinase (CK)/phosphocreatine (PCr) system in the energy metabolism of skeletal muscle. As a test system we compared hindlimb muscle of knockout mice lacking the cytosolic M-type (M-CK(-)/(-)), the mitochondrial ScMit-type (ScCKmit(-)/(-)), or both creatine kinase isoenzymes (CK(-)/(-)), and in vivo 31P-NMR was used to monitor metabolic responses during and after an ischemic period. Although single mutants show some subtle specific abnormalities, in general their metabolic responses appear similar to wild type, in contrast to CK(-)/(-) double mutants. This implies that presence of one CK isoform is both necessary and sufficient for the system to be functional in meeting ischemic stress conditions. The global ATP buffering role of the CK/PCr system became apparent in a 30% decline of ATP in the CK(-)/(-) mice during ischemia. Both M-CK(-)/(-) and CK(-)/(-) showed increased phosphomonoester levels during ischemia, most likely reflecting adaptation to a more efficient utilization of glycogenolysis. While in M-CK(-)/(-) muscle PCr can still be hydrolyzed to provide Pi for this process, in CK(-)/(-) muscle only Pi from ATP breakdown is available and Pi levels increase much more slowly. The experiments also revealed that the system plays a role in maintaining pH levels; the CK(-)/(-) mice showed a faster and more pronounced acidification (pH = 6.6) than muscles of wild type and single knockout mutants (pH = 6.9).

Topics: Adenosine Triphosphate; Animals; Creatine Kinase; Energy Metabolism; Female; Glycogen; Glycolysis; Ischemia; Isoenzymes; Lactates; Male; Mice; Mice, Inbred C57BL; Mice, Knockout; Muscle, Skeletal; Nuclear Magnetic Resonance, Biomolecular; Oxidative Phosphorylation

In order to examine glucose metabolism in liver grafts after cold ischemia and reperfusion, the heterogeneous lobular distribution pattern of glycogen content and glucose-6-phosphatase activity was studied using histochemical methods. The characteristic heterogeneous lobular distribution pattern of glycogen and glucose-6-phosphatase was maintained after preservation and reperfusion. However, it appeared that glycogen content decreased in both periportal and centrilobular hepatocytes after reperfusion. The glycogen decrease was higher in periportal hepatocytes. Glucose-6-phosphatase activity was maintained after reperfusion in most of the cases in periportal hepatocytes. In centrilobular hepatocytes, more cases showed a decrease in enzyme activity. It is suggested that ischemia-reperfusion mainly affects the glycogen content in both periportal and centrilobular hepatocytes and that centrilobular glucose-6-phosphatase activity is more sensitive to ischemia-reperfusion injury than periportal hepatocytes.

Topics: Adolescent; Adult; Biopsy; Child; Cryopreservation; Glucose-6-Phosphatase; Glycogen; Humans; Ischemia; Liver; Liver Transplantation; Middle Aged; Reperfusion Injury; Transplantation, Homologous

Although discontinuous total parenteral nutrition (d-TPN) has recently been favored for clinical use over continuous total parenteral nutrition (c-TPN) to ameliorate liver dysfunction, mechanisms for the protection against postoperative liver dysfunction remain unknown. This study aimed to examine differences in mitochondrial function in d-TPN- and c-TPN-pretreated livers during ischemia-reperfusion. Rat livers pretreated with d-TPN or c-TPN were perfused with Krebs-Ringer buffer and were exposed to 25% low-flow hypoxia followed by reperfusion. Intrahepatic mitochondrial membrane potential (triangle up) and cell viability were assessed by dual-color digital microfluorography using rhodamine 123 (Rh123) and propidium iodide (PI), respectively. In response to hypoxia, livers pretreated with c-TPN, d-TPN, and an ordinary chow diet exhibited a significant triangle up reduction among the entire lobules. Upon reperfusion, the regional triangle up values further decreased in the c-TPN liver, whereas those in the d-TPN-treated or chow-treated livers displayed a rapid recovery toward the control levels. The severity of cell injury did not differ among the groups, showing that the reperfusion-induced triangle up drop in the c-TPN-pretreated liver is not a consequence of cell injury. Differences in the triangle up drop among the groups appear to occur irrespective of those in the glycogen storage, because the livers undergoing d-TPN display a marked triangle up recovery even when reperfused at the end of a fasted state. These results indicate that c-TPN, but not d-TPN, jeopardizes mitochondrial re-energization and suggest that a circadian pattern of the TPN serves as a potentially beneficial strategy to reduce the risk of postischemic mitochondrial dysfunction in the liver.

Topics: Animals; Bile; Cell Survival; Fluorescent Dyes; Glycogen; Intracellular Membranes; Ischemia; Liver; Liver Diseases; Male; Membrane Potentials; Mitochondria, Liver; Nutritional Status; Parenteral Nutrition, Total; Phagocytosis; Rats; Rats, Wistar; Reperfusion Injury; Rhodamine 123

Relationships between pH and the concentrations of phosphocreatine (PCr), inorganic phosphate (Pi), and lactate during ischemic exercise depend on passive buffering, proton consumption as a consequence of net PCr breakdown, the control of glycogenolysis, (particularly in relation to the concentration of Pi, a substrate of glycogen phosphorylase that is produced by net PCr breakdown), and the creatine kinase equilibrium. The author analyzes the implications of these relationships for the interpretation of 31P-magnetic resonance spectroscopic data and for the control of glycogenolysis. For realistic adenosine diphosphate (ADP) concentrations, given the constraints of the creatine kinase equilibrium, the pH must be near-linear with lactate, with an apparent buffer capacity (i.e., the ratio of lactate accumulation to pH change) that is nearly twice the true buffer capacity (i.e., the ratio of net proton loading to pH change). The implications for glycogenolytic control depend on adenosine triphosphate (ATP) turnover, but an upper limit of activation of glycogen phosphorylase (i.e., the amount of the a form) that would permit no increase in ADP concentration can be calculated. Phosphorylase activation during ischemic exercise seems approximately proportional to the power output, consistent with calcium stimulation of phosphorylase b kinase. In simulations, ADP concentration is highly sensitive to this proportionality, as (unlike in purely oxidative exercise) ADP concentration is not known to participate in any closed feedback loops in ischemic exercise.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Buffers; Computer Simulation; Exercise; Glycogen; Humans; Hydrogen-Ion Concentration; Ischemia; Lactates; Magnetic Resonance Spectroscopy; Muscles; Phosphates; Phosphocreatine; Phosphorus

Adenine nucleotides and glycogen are degraded in skeletal muscle during no-flow ischaemia. Past investigations have ascribed these metabolic changes to the severe energetic stress which arises with the removal of exogenous substrates (principally oxygen). We tested this hypothesis by measuring the high-energy phosphagen and glycogen contents of stimulated rat hindlimb muscles (1 twitch s-1) prior to and following 40 min of no-flow ischaemia or hypoxic perfusion without glucose (PaO2 = 4.6 +/- 0.1 torr, plasma glucose = 0.3 +/- 0.1 mmol L-1). Both experimental protocols eliminated exogenous substrate supply; however, the maintenance of flow during hypoxic perfusion ensured the removal of metabolic by-products. A period of forty minutes of skeletal muscle ischaemia was characterized by reductions in the total adenine nucleotide pool, phosphocreatine and glycogen in the slow oxidative soleus, fast oxidative-glycolytic plantaris and the fast glycolytic white gastrocnemius. Compared to ischaemia, the total adenine nucleotide pool was higher (by 7.2-13.3 mumol g-1 dry wt) and the glycogen content lower (by 10.0-16.6 mumol g-1 dry wt) in skeletal muscle exposed to hypoxic perfusion without glucose. The ability of hypoxic perfusion to attenuate TAN degradation and augment glycogenolysis can be attributed to metabolic by-product removal. By limiting muscle lactate and PCO2 accumulation, hypoxic perfusion without glucose attenuates cellular acidification; this could in turn limit AMP deaminase activation and glycogen phosphorylase inhibition. We conclude that the ischaemia-induced alterations in adenine nucleotide and glycogen metabolism arise in response to the elimination of exogenous substrates and to the accumulation of metabolic by-products.

Topics: Adenine Nucleotides; Animals; Blood Glucose; Energy Metabolism; Glycogen; Hindlimb; Hydrogen-Ion Concentration; Ischemia; Male; Muscle Contraction; Muscle, Skeletal; Rats; Rats, Sprague-Dawley; Regional Blood Flow

The metabolic effects of partial ischemia on canine skeletal muscle were examined during 20 min of isometric contraction. A reduction in blood flow of approximately 75% resulted in an approximate 40% reduction in contractile function. Muscle lactate accumulation and phosphocreatine (PCr) hydrolysis were greater during ischemia, indicating a greater reliance on anaerobic ATP regeneration. Pyruvate dehydrogenase transformation to its active form (PDCa) during contraction was not affected by ischemia, such that PDCa did not appear to be a determinant of skeletal muscle fatigue. Acetylcarnitine concentration was greater during ischemic contraction and inversely correlated with PCr concentration (r = -0.79, P<0.01). Furthermore, acetylcarnitine accumulation and PCr degradation correlated with the degree of skeletal muscle fatigue (r = 0.56, P<0.05 and r = 0.70, P<0.01, respectively). Thus the greater the acetyl group oxidation, the lesser the contribution from anaerobic ATP provision and, subsequently, the smaller the degree of muscle fatigue observed. The metabolic characteristics of this model of ischemic muscle contraction are indistinguishable from the normal metabolic responses observed with increasing contractile intensity.

Topics: Acetylcarnitine; Adenosine Triphosphate; Animals; Dogs; Electric Stimulation; Energy Metabolism; Fatty Acids, Nonesterified; Female; Glycogen; Ischemia; Isometric Contraction; Kinetics; Lactates; Muscle Fatigue; Muscle, Skeletal; NAD; Phosphocreatine; Pyruvate Dehydrogenase Complex; Regional Blood Flow; Regression Analysis; Time Factors

Previously we have shown that hypercarbia produces a larger decrease in agonal glycolytic rate in 1-month-old swine than in newborns. In an effort to understand the mechanism responsible for this difference, we tested the hypothesis that hypercarbia produces age-related changes in the concentration of one or more effectors of phosphofructokinase activity. Specifically, in vivo 31P and 1H NMR spectroscopy was used to compare changes in lactate levels, intracellular pH, free magnesium concentration, and content of phosphorylated metabolites for these two age groups at three intervals during the first 1.5 min of complete ischemia in the presence or absence of hypercarbia (PaCO2 = 102-106 mm Hg). Hypercarbia produced the same drop in intracellular brain pH for both age groups, but the decrease in phosphocreatine level and increase in inorganic phosphate content were greater in 1-month-olds compared with newborns. During ischemia there was no difference between the magnitude of change in intracellular pH and levels of phosphocreatine and inorganic phosphate in hypercarbic 1-month-olds versus newborns. Under control conditions, i.e., normocarbia and normoxia, the free Mg2+ concentration was lower and the fraction of magnesium-free ATP was higher for newborns than 1-month-olds. However, there was no change in these variables for either age group during hypercarbia and early during ischemia. Thus, age-related differences in the relative decrease in agonal glycolytic rate during hypercarbia could not be explained by differences in intracellular pH, inorganic phosphate content, or free magnesium concentration. The [ADP]free at control was higher in newborns compared with 1-month-olds, and there was no age-related difference in [AMP]free. These variables did not change for newborns when exposed to hypercarbia, but for 1-month-olds [ADP]free and [AMP]free increased during hypercarbia relative to control values. High-energy phosphate utilization during ischemia for hypercarbic 1-month-olds was reduced by 74% compared with normocarbic 1-month-olds during ischemia, whereas the reduction in energy utilization (14%) was not significant for hypercarbic versus normocarbic newborns during ischemia.(ABSTRACT TRUNCATED AT 400 WORDS)

Topics: Acidosis; Animals; Animals, Newborn; Brain; Brain Chemistry; Death; Glycogen; Hydrogen; Hydrogen-Ion Concentration; Hypercapnia; Ischemia; Lactates; Magnesium; Magnetic Resonance Spectroscopy; Phosphorus; Swine; Swine, Miniature

Topics: Adult; AMP Deaminase; Energy Metabolism; Exercise; Glycogen; Humans; Inosine Monophosphate; Ischemia; Lactic Acid; Male; Muscle Contraction; Muscle Fibers, Fast-Twitch; Muscle Fibers, Slow-Twitch; Muscle, Skeletal; Physical Exertion; Purines

Fast skeletal muscles of Sprague-Dawley rats [tibialis anterior (TA) and extensor digitorum longus (EDL)] were subjected to ischemia by unilateral ligation of the common iliac artery. In some animals, ischemia was combined with indirect electrical stimulation at 10 Hz either for 3 x 2 h (strenuous activity) or for 7 x 10-min bouts/day (mild activity). After 2 wk, muscle blood flow and fatigue were measured during 5-min isometric supramaximal twitch contractions at 4 Hz. Terminal arteriole diameters were assessed in TA by intravital microscopy at rest and during contractions. Vascular perfusion pressure in the muscles was estimated from measurements in the carotid and saphenous arteries below the site of ligation. Capillary supply was expressed in TA and EDL as capillary-to-fiber ratio on the basis of histochemical staining for capillaries. Strenuous stimulation of ischemic muscles increased their atrophy, failed to restore blood flow, and actually worsened fatigue. In contrast, mild stimulation improved perfusion pressure, increased capillary-to-fiber ratio in the glycolytic part of TA, restored dilatation of terminal arterioles during muscle contractions, and improved blood flow and muscle fatigue so that they were no longer significantly different from control muscles. Thus, an attenuated intermittent protocol may be indicated in the treatment of muscle ischemia.

Topics: Animals; Arterioles; Blood Pressure; Capillaries; Chronic Disease; Electric Stimulation; Glycogen; Hindlimb; Ischemia; Male; Muscle Fatigue; Muscle Fibers, Skeletal; Muscle, Skeletal; Rats; Rats, Sprague-Dawley

The influence of graded leg muscle ischaemia on the adaptation to training and on the acute response to exercise was studied in healthy subjects. Graded ischaemia during supine exercise was induced by application of 50 mmHg external pressure on the legs. This procedure reduced leg blood flow by 16%, venous oxygen saturation by 12 percentage units, and markedly increased lactate release (p < 0.05 for all). One-legged training was performed during four weeks, 4 sessions per week. Each session started with one leg training for 45 min with reduced blood flow (ischaemic training). The contralateral leg, serving as a control, was then trained with an identical power-output profile for 45 min but without flow restriction (non-ischaemic training). Ischaemic training enhanced the adaptation to training. Peak oxygen uptake and time to fatigue increased more (p < 0.05) with ischaemic than with non-ischaemic training. Citrate synthase activity, capillaries per fibre, and glycogen content were greater (p < 0.05) in the trained than in the detrained state. In the ischaemically trained leg, the type IIb fibre proportion was lower (p < 0.05) and the I fibre proportion tended to be higher (p = 0.06) in the trained than in the detrained state. Maximum voluntary dynamic strength was decreased by 8% (p < 0.01) in the ischaemically trained leg, but was unaffected in the non-ischaemically trained leg. During acute ischaemic exercise, as compared to non-ischaemic exercise, there was a higher degree of glycogen depletion, a greater depletion of type II, but not of type I fibres, a greater electromyographic activity, higher catecholamine concentrations, lower intramuscular ATP and creatine phosphate content, and an increased nitric oxide formation as estimated by increased plasma nitrate content. In conclusion, the mechanisms underlying the potentiation of the adaptation to training by ischaemia are assumed to depend on the operation of stimuli which were amplified during acute ischaemic exercise.

Topics: Acute Disease; Adaptation, Physiological; Adenosine Triphosphate; Adolescent; Adult; Biopsy; Blood Flow Velocity; Blood Gas Analysis; Capillaries; Catecholamines; Citrate (si)-Synthase; Electromyography; Exercise Therapy; Glycogen; Humans; Ischemia; Lactates; Lactic Acid; Leg; Male; Models, Cardiovascular; Muscles; Nitric Oxide; Oxygen; Oxygen Consumption; Phosphocreatine

Eight healthy men performed supine one-legged training on a bicycle ergometer 45 min per leg four times per week for 4 week. The ergometer and lower body were inside a pressure chamber, the opening of which was sealed at the level of the crotch. One leg trained with impeded leg blood flow (I-leg), induced by an increased (50 mmHg) chamber pressure, at the highest tolerable intensity. The contralateral leg trained at the same power under normal pressure (N-leg). Before and after training biopsies were taken from the vastus lateralis of both legs and maximal one-legged exercise tests were executed with both legs. Biopsies were repeated when the subjects had been back to their habitual physical activity for 3 months. Training increased exercise time to exhaustion, but more in the I-leg than in the N-leg. After training, the I-leg had higher activity of citrate synthase (CS), a marker of oxidative capacity, and lower activity of the M-subunit of lactate dehydrogenase isoenzymes. It also had a higher percentage of type-I fibres and a lower percentage of IIB fibres, larger areas of all fibre types and a greater number of capillaries per fibre. It is concluded that ischaemic training changes the muscle metabolic profile in a direction facilitating aerobic metabolism. An altered fibre-type composition may contribute, but is not enough prerequisite for the change.

Topics: Adult; Capillaries; Citrate (si)-Synthase; Exercise Test; Glycogen; Glycolysis; Humans; Ischemia; Isoenzymes; L-Lactate Dehydrogenase; Leg; Male; Muscles; Oxidation-Reduction; Phosphofructokinase-1; Physical Education and Training; Physical Exertion; Regional Blood Flow

Changes in the metabolites phosphocreatine (PCr), Pi and ATP were quantified by 31P n.m.r. spectroscopy in the human calf muscle during isometric contraction and recovery under ischaemic conditions. Time resolution of the measurements was 10 s. During a 30-60 s ischaemic isometric contraction, PCr decreased linearly at a rate of 1.17%/s (relative to the resting value) at a contraction strength equivalent to 70% of the maximal voluntary contraction (MVC) and at a rate of 2.43%/s at 90% MVC. There was a corresponding increase in Pi but the concentration of ATP did not change. pH decreased linearly during contraction by 4.22 and 8.23 milli-pH units/s at 70 and 90% MVC respectively. During a subsequent 5 min interval of ischaemic recovery, PCr, Pi, ATP, phosphomonoesters and calculated free ADP, free AMP and pH retained the value they had attained by the end of contraction with no significant recovery. Thus it is concluded that anaerobic glycolysis and glycogenolysis is halted momentarily on termination of contraction and that PCr is not resynthesized during ischaemic recovery. This paradoxical arrest of glycolytic flow in spite of the very significantly elevated concentration of potent activators such as Pi and free AMP clearly indicates that parameters other than PCr, ATP, Pi, calculated pH, free ADP and free AMP regulate glycolysis and glycogenolysis of human skeletal muscle very efficiently under ischaemic conditions.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Adult; Glycogen; Glycolysis; Humans; Hydrogen-Ion Concentration; Ischemia; Isometric Contraction; Kinetics; Magnetic Resonance Spectroscopy; Male; Muscles; Phosphates; Phosphocreatine

Muscle performance and structure was studied in rat soleus muscle with limited blood supply in combination with chronic muscle stimulation. Blood supply to the lower leg was restricted by ligation of the common iliac artery, electrodes were implanted in the vicinity of the sciatic nerve and ankle flexors were denervated. Three days later, soleus and gastrocnemius muscles were stimulated at 4 Hz four times a day for a period of 20 min with 2 h intervals between stimulations; this procedure was continued for 4 days. Muscle performance, histochemistry and ultrastructure were studied on the eighth day after operation in these muscles and in ischaemic unstimulated muscles with denervated ankle flexors. Both were compared with control animals. Muscles with limited blood supply developed less isometric twitch tension than control muscles (peak twitch tension in ischaemic muscle was 60.3 +/- 4.8 g g-1 muscle, mean +/- S.E.M., compared to 79.7 +/- 6.9 g g-1 in control muscle; tensions after 5 min contraction were 54.5 +/- 5.5 g g-1 in ischaemic muscle compared to 70.6 +/- 6 g g-1 in controls). Stimulated muscles with limited blood supply had higher peak (85 +/- 16.6 g g-1) and final (87 +/- 12 g g-1) tensions, and also fatigued less than muscles with limited blood supply but no stimulation. Histochemical estimation of capillary density (by staining for alkaline phosphatase) and slow (SO) and fast (FOG) fibres (by myosin ATPase staining) revealed similar capillary to fibre ratios (2.5) and a similar proportion of FOG fibres (around 18%) in all muscles. The proportion of glycogen-depleted fibres (estimated from the periodic acid Schiff reaction, PAS) in muscles removed from animals 10 min after a 5 min period of isometric twitches was significantly lower in ischaemic muscles (45.1 +/- 1.9%) than in control (80.5 +/- 1.5%) or chronically stimulated ischaemic muscles (67.3 +/- 4.0%). Electron microscopy showed disorganised myofibrils with Z-line streaming in 7.48 +/- 3.04% of fibres in muscles with limited blood supply. Swollen and degenerated mitochondria, dilated sarcoplasmic reticulum and areas of disrupted sarcolemma were also observed. Stimulated ligated muscles showed a significantly lower proportion of fibres with disorganised filaments (0.65 +/- 0.32%) and other signs of damage were much less frequent. The reduced damage and improved performance of chronically stimulated slow muscle may be the result of improved microcirculation, preventing accumulation of lac

Topics: Animals; Capillaries; Electric Stimulation; Glycogen; Ischemia; Microscopy, Electron; Muscle Contraction; Muscle Denervation; Muscles; Rats; Rats, Inbred Strains

1. Ischaemia was applied for 30 min to the liver of Wistar rats and of gsd/gsd rats, which have a genetic deficiency of phosphorylase kinase. The rate of glycogenolysis corresponded closely to the concentration of phosphorylase a. The loss of glycogen from Wistar livers was accounted for by the intrahepatic increase in glucose plus lactate. Further, the accumulation of oligosaccharides was negligible in the gsd/gsd liver. 2. Isolated hepatocytes from Wistar and gsd/gsd rats were incubated for 40 min in the presence of either KCN or glucagon. Again, the production of glucose plus lactate was strictly dependent on the presence of phosphorylase a. However, the catalytic efficiency of phosphorylase a was about 2-fold higher in the presence of KCN. 3. We conclude that the hepatic glycogenolysis induced by anoxia and by KCN is solely mediated by phosphorylase a. The higher catalytic activity of phosphorylase a under these circumstances could be due to an increased concentration of the substrate Pi.

Topics: Animals; Catalysis; Cyanides; Glucose; Glycogen; In Vitro Techniques; Ischemia; L-Lactate Dehydrogenase; Lactates; Lactic Acid; Liver; Phosphorylase a; Phosphorylase Kinase; Phosphorylases; Potassium Cyanide; Rats; Rats, Inbred Strains

Breast muscle of young chicks fed chow diets containing the creatine analog 1-carboxymethyl-2-iminoimidazolidine (cyclocreatine) accumulated up to 40 mumol/g wet weight of the synthetic phosphagen 1-carboxymethyl-2-imino-3-phosphonoimidazolidine (cyclocreatine-P2-). ATP levels were sustained at high values substantially longer in breast muscle of cyclocreatine-fed chicks, compared to control-fed chicks, during total ischemia initiated 2 h after injection of both groups with the beta-adrenergic agonist isoproterenol (5 mg/kg subcutaneous). For example, in chicks fed 0.5% cyclocreatine for 10-19 days ATP levels in isoproterenol-stimulated breast muscles after 1 h of ischemia at 37 degrees C were 6.1 mumol/g, compared to 1.9 mumol/g for the control-fed group, and after 2 h of ischemia were 3.5 mumol/g compared to 0.6 mumol/g for controls. Creatine-P reserves in isoproterenol-stimulated breast muscles of all dietary groups were essentially exhausted within the first hour of ischemia. In contrast, breast muscle of chicks fed either 1 or 0.5% cyclocreatine still contained 28 and 19 mumol/g of cyclocreatine-P, respectively, after 1 h of ischemia; after 2 h of ischemia, the respective cyclocreatine-P values were 20 and 13 mumol/g. Isoproterenol-stimulated chick breast muscle provides the first skeletal muscle model system for studying the molecular mechanisms by which dietary cyclocreatine helps sustain ATP levels during ischemia. Although adaptive factors are also involved, it is suggested that a significant portion of the ATP-sustaining activity of dietary cyclocreatine in ischemic breast muscle can be attributed to the unique thermodynamic properties of the accumulated cyclocreatine-P. These properties enable cyclocreatine-P to continue to thermodynamically buffer the adenylate system and transport high energy phosphate throughout the long muscle fibers at cytosolic pH values and phosphorylation potentials well below the range where the creatine-P system can function effectively. Synergism between glycolysis and this long-acting synthetic phosphagen might well help delay depletion of ATP levels in skeletal muscles during ischemia. Cyclocreatine feeding provides a unique experimental tool for quantitative evaluation of the proposed protective role of ATP against irreversible cellular damage in skeletal and cardiac muscles during ischemic episodes.

Topics: Adenosine Triphosphate; Animals; Chickens; Glycogen; Imidazolidines; Ischemia; Isoproterenol; Kinetics; Lactates; Male; Muscles; Phosphocreatine

Rat kidneys were made ischemic for 5 to 120 seconds. Segments of individual nephrons were dissected from freeze dried sections and analyzed for ATP, phosphocreatine, glycogen, glucose, glucose-6-phosphate, lactate and creatine kinase. ATP fell most rapidly in proximal convoluted and straight tubules (PCT, PST) and distal convoluted tubules (DCT), and most slowly in glomerulus and papilla. Phosphocreatine levels ranged fivefold and was highest in DCT, where it approached that of brain. Creatine kinase ranged 100-fold with lowest level in PCT, where the ischemic fall in phosphocreatine was so slow as to suggest a function other than that of an energy reserve. Glycogen varied tenfold from modest levels in distal segments to very low levels in PST, and was not used rapidly in any segment. Glucose consumption and lactate production were most rapid in distal portions. High-energy phosphate consumption for the first 7.5 seconds of ischemia, calculated from these data, indicates roughly-equal energy metabolism in proximal and distal segments, with lower levels in papilla, and especially in glomerulus. The absolute values suggest that the in vivo metabolic rate of the nephron continued almost unabated for 5 or 10 seconds of ischemia.

Topics: Adenosine Triphosphate; Animals; Creatine Kinase; Energy Metabolism; Glucose; Glycogen; Ischemia; Kidney; Kidney Glomerulus; Kidney Medulla; Kidney Tubules; Kinetics; Lactates; Lactic Acid; Male; Nephrons; Phosphocreatine; Rats; Rats, Inbred Strains

Pedicled skin flaps in the pig have been used to investigate the effects of 3-h ischemia and reperfusion on the epidermal metabolism of glycogen and glucose. Epidermal glycogen content fell steadily at a rate of about 1.2 mumol of glucose-equivalents per g wet weight per h whereas the rate of glucose consumption declined from 1.8 mumol per g wet weight during the first hour to about 0.25 mumol per g wet weight in the third hour. During ischemia the proportion of glycogen synthase in the I form increased progressively from an initial value of about 8% to about 70%, but the proportion of phosphorylase in the a form decreased only in the third hour of ischemia. The concentration of ATP decreased and ADP and AMP increased but the total pool of epidermal adenine nucleotides was not depleted. On reperfusion, these changes were reversed and normal epidermal concentrations of glucose and adenine nucleotides were restored within 30 min and remained stable thereafter. The resynthesis of glycogen proceeded at a steady rate of about 1 mumol per h per g wet weight and the phosphorylation state of both glycogen synthase and phosphorylase approached normal values after 3 h. It is concluded that epidermal glycogenolysis in ischemia is, at least in part, a consequence of activation of phosphorylase b by AMP, and that glycogen resynthesis on reperfusion is promoted by the ischemic activation of glycogen synthase.

Topics: Adenine Nucleotides; Animals; Epidermis; Female; Glucose; Glycogen; Glycogen Synthase; Ischemia; Oxygen; Phosphorylases; Regional Blood Flow; Skin; Swine

To evaluate the temporal relationship and potential correlation between intramuscular phosphagen levels, lipid oxidation, and extent of muscle injury, a canine gracilis muscle model was used to study the consequences of a global ischemic episode for up to 7 h duration with reperfusion for 4 h. In this model the contralateral gracilis muscle was prepared identically to the test side but was not subjected to ischemia and thus served as a control. Blood flow, oxygen consumption, and lactate and glycerol release were measured before and after 2- and 7-h ischemic stress periods. The intramuscular metabolites, glycogen, lactate, phosphocreatine, and ATP, as well as free fatty acid conjugated dienes, were measured before, during, and after the ischemic insult. A 2-h ischemic insult resulted in minimal ultrastructural damage and complete regeneration of intramuscular phosphagens and glycogen on reperfusion with complete normalization of lipid oxidation products. In contrast, a 7-h ischemic insult resulted in profound injury at the ultrastructural level with an inability to restore intramuscular phosphagens and glycogen on reperfusion. This severe muscle injury correlated with a 2.5-fold increase in lipid oxidation products (free fatty acid conjugated dienes) and a decline in ATP levels below 5 mumol/g dry wt on reperfusion. Our results emphasize the prolonged glycolytic activity of skeletal muscle during global ischemia and document the increased production of oxygen free radical-mediated lipid oxidation products in irreversibly injured muscle.

Topics: Adenosine Triphosphate; Animals; Dogs; Fatty Acids, Nonesterified; Glycogen; Ischemia; Lactates; Lactic Acid; Lipid Peroxides; Microscopy, Electron; Muscles; Oxygen Consumption; Phosphocreatine; Regional Blood Flow; Time Factors

The protective effect of local hypothermia was studied in pig's limbs made ischaemic by long, repeated application of a pneumatic tourniquet. Twenty-one Landrace pigs were anaesthetised on two separate occasions six days apart and a pneumatic tourniquet at 500 mmHg pressure was applied to the same forelimb for three and two hours respectively. Ten of the pigs had local hypothermia from cold gel packs placed around the limb during the first tourniquet application; the other 11 had the ischaemic limb exposed to room temperature. In comparison with the normothermic limbs, the hypothermic ischaemic limbs had significant slowing of metabolism. The hypothermic limbs also showed less inflammatory response and a faster rate of recovery, both immediately after removal of the tourniquet, and by the end of the experiment, 10 days after the first tourniquet. Local hypothermia produced by this technique was shown to be safe and effective, while appearing to protect muscles exposed to prolonged tourniquet-induced ischaemia.

Topics: Animals; Body Temperature; Forelimb; Glycogen; Hydrogen-Ion Concentration; Hypothermia, Induced; Ischemia; Lactates; Muscles; Phosphofructokinase-1; Potassium; Swine; Tourniquets

The effect of energy substrate depletion and of high lactic acid (LA) load on the development of irreversible cell injury was evaluated in the lateral gastrocnemius muscle of rabbits subjected to 4 hr of tourniquet hindlimb ischemia. Three groups of animals were studied. Group I, high ATP-ischemia, these animals were subjected to 4 hr of ischemia; group II, low ATP--low LA ischemia, in this group the gastrocnemius muscle was electrically stimulated for 5 min during ischemic conditions to reduce the glycogen store, a short reperfusion period was allowed after the stimulation in order to wash out the built up LA, and the muscle was then subjected to 4 hr of ischemia; group III, low ATP--high LA ischemia, in this group glycogen was depleted as in group II, but no reperfusion period was allowed before the 4 hr period of ischemia. In group I, ATP levels were well preserved during the ischemic period, whereas in the substrate-deprived groups (II and III) a rapid depletion of ATP and phosphocreatine (CP) occurred. The LA was twice as high in the "high LA" group (III) as in the "low LA" group (II) during the ischemic period. The extent of injury was evaluated after 24 hr of reperfusion by measuring ATP and CP content, and contractile force and by light microscopy. No or minor cell damage was found in group I. In group III--high LA--no recovery was obtained in any of the variables used for evaluation. In group II--Low LA--there was a certain recovery. ATP and CP increased to about 35% and contractile force to 25% of control. Morphologically about 20% of the muscle cells appeared to be unaffected by the ischemic insult. It is concluded that reduction of the glycogen available for ATP resynthesis during the ischemic period drastically reduces the ability of skeletal muscle to withstand prolonged ischemia. A high LA load seems to amplify the deleterious effects of a low initial substrate level.

Topics: Adenosine Triphosphate; Animals; Electric Stimulation; Glycogen; Ischemia; Lactates; Lactic Acid; Male; Muscle Contraction; Muscles; Phosphocreatine; Rabbits; Time Factors

Metabolic changes in blood and skeletal muscle of dogs before, during and after tourniquet ischaemia were investigated to obtain further information on cellular metabolic abnormalities and restitution during and following long-lasting blood flow interruptions. Total carbohydrate and glycogen contents in the muscle tissue fell during ischaemia and remained significantly decreased even 1 h after recirculation due to inhibition of glycogen synthetase activity. Muscle glucose concentration remained stable during ischaemia and was significantly elevated 1 h after tourniquet release. In contrast, muscle lactate concentration was elevated during ischaemia and normal after recirculation. Blood lactate, pyruvate and serum inorganic phosphate concentrations increased markedly after tourniquet release and were still significantly elevated 1 h after recirculation, whereas ketone bodies and citric acid cycle intermediates remained unchanged. Tourniquet ischaemia had no effect on muscle phosphate concentration or on the activities of proteases, protease inhibitors or hydrolases in the blood. Nevertheless, our results clearly indicate metabolic abnormalities in the blood and skeletal muscle during 5 h of tourniquet ischaemia and even after 1 h of recirculation.

Topics: 3-Hydroxybutyric Acid; Acetoacetates; Animals; Citrates; Citric Acid; Dogs; Energy Metabolism; Female; Glycogen; Glycogen Synthase; Glycolysis; Hydroxybutyrates; Ischemia; Ketoglutaric Acids; Lactates; Lactic Acid; Lysosomes; Male; Muscles; Phosphorylases; Pyruvates; Pyruvic Acid; Tourniquets

In addition to the determination of the presenting symptom of patients with peripheral vascular occlusive disease, evaluation of these patients may include the noninvasive measurements of ankle/arm pressure ratio, limb blood flow, and treadmill testing to evaluate the severity of the reduction in blood flow. We have included metabolic studies to assess the effect of this reduced blood flow in patients with stable intermittent claudication (n = 20), and with end-stage ischemia (night and rest pain) (n = 11), and in a control group without vascular disease (n = 8). No correlations were found between the resting limb blood flow, ankle/arm pressure ratios, maximum walking distance, and stated walking distance for the patients with stable claudication. Although the oxygen consumption was reduced only in the patients with end-stage ischemia, the percent oxygen extraction was increased to the same level in the patients with stable claudication and those with end-stage ischemia. Intramuscular stores of high-energy phosphates and glycogen were maintained in all groups with the lactate/pyruvate ratio increased only in the patients with end-stage ischemia. The complex interrelationships between the rate and distribution of blood flow with exercise and enzyme adaptation in patients with vascular disease make current resting hemodynamic and metabolic evaluations a poor reflection of the severity of the clinical condition within each patient group. Therefore laboratory testing may offer no advantage over clinical presentation in the overall evaluation of these patients.

Topics: Adenosine Triphosphate; Adult; Aged; Blood Pressure; Glycogen; Humans; Intermittent Claudication; Ischemia; Lactates; Lactic Acid; Leg; Middle Aged; Muscles; Oxygen Consumption; Phosphocreatine; Pyruvates; Pyruvic Acid; Regional Blood Flow

Intracellular pH (pHi) was measured with double-barrelled microelectrodes during 4 h of complete tourniquet ischemia in rabbit gastrocnemius muscle (group I). The pHi was related to extracellular pH (pHe), membrane potential (Em), tissue lactic acid (LA) and ATP. A fall in pHi from 7.00 +/- 0.03 to 6.60 +/- 0.05 occurred during 4 h of ischemia, with a slight pH-drop (0.07 pH units) during the initial hour and a more pronounced drop of 0.13 pH units during the last hour of ischemia. These changes were paralleled by a considerable decrease in pHe from 7.30 +/- 0.01 to 6.36 +/- 0.05 and a sixfold increase of tissue LA. The buffering capacity during the 4 h of ischemia was estimated to 81.9 +/- 5.6 mmol H+/l X pH. In parallel with the reduction in pHe, the resting membrane potential decreased from -90 mV and stabilised at around -60 mV after 2 h of ischemia. A less negative cell interior would favour H+ extrusion since the Em-EH+ gradient was unchanged at about -70 mV during the entire period of ischemia. This could contribute to muscle fiber buffering during ischemia. In another set of experiments (group II) the muscular glycogen reserve was reduced 20 min prior to a 4 h period of ischemia. Thereby an ischemic state was created where ATP levels decreased to 30% of initial, in contrast to the unaltered ATP content in group I.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Adenosine Triphosphate; Animals; Body Fluids; Extracellular Space; Glycogen; Hydrogen-Ion Concentration; Intracellular Fluid; Ischemia; Lactates; Male; Membrane Potentials; Muscles; Rabbits

The effect of preischaemic glycogen-depletion on the development of skeletal muscle injury was investigated in rats subjected to tourniquet hind-limb ischaemia. Glycogen depletion was performed by direct electrical stimulation of the extensor digitorum longus (EDL) muscle during ischaemic conditions. The metabolite load during the subsequent 2.5 h of ischaemia was modified by allowing, or not allowing, a short reperfusion period after termination of the electrical stimulation. The extent of injury was evaluated morphologically after 5 or 15 h of reperfusion, by the combination of an intravital dye exclusion test and a histochemical staining, demonstrating calcium-precipitates-Alizarin red S. Minimal damage was found in animals subjected to ischaemia without preceding glycogen depletion. In both groups of preischaemically glycogen-depleted animals, significant irreversible injury occurred. The injury was significantly less in animals in which a wash-out period was allowed after termination of stimulation. Fast-glycogenolytic fibres (FG) were most sensitive to the ischaemic insult during both experimental conditions, while slow-oxidative fibres (SO) were spared. Fast-oxidative-glycogenolytic fibres (FOG) showed an intermediate response. The injury seemed to be established after 5 h of reperfusion, indicating that cells react with an all-or-nothing response in the present model.

Topics: Animals; Electric Stimulation; Glycogen; Histocytochemistry; Ischemia; Muscles; Perfusion; Rats; Rats, Inbred Strains

The authors carried out histochemical determinations of the glycogen level and the activity of some enzymes controlling carbohydrate metabolism (glycogen transferase and phosphorylase, succinate dehydrogenase) in the lumbar segments of the spinal cord of 40 animals (cats) with circulatory ischemia caused by aorta ligation. The examinations were performed at different periods of time after the ischemia induction under conditions of carbohydrate load. In the course of the pathological process development because of the ischemia (within a period ranging from 6 hours to 26 days) considerable variations of the glycogen-synthetizing capacities of the spinal cord nervous elements were revealed. These variations were of a periodic character. The number of glycogen-containing cells was maximal within a period ranging from the 2nd to the 10th day: this correlated with the highest enzymatic activity in this period. The glycogen content in a cell and the degree of the latter's damage were found to be in an inverse relationship. It is shown that different resistance of the nervous elements to hypoxia is determined to a great measure by their capacity to synthetize and deposit glycogen. Thus, the glycogen metabolism, being a specific compensatory-adaptive mechanism of the nervous tissue, is, thereby, a material basis of its vital activity.

Topics: Animals; Cats; DNA; Glycogen; Glycogen Synthase; Histocytochemistry; Ischemia; Phosphorylases; RNA; Spinal Cord; Succinate Dehydrogenase

Temporary infrarenal clamping of the aorta during reconstructive surgery induces incomplete ischemia of the leg muscle. After release of the clamp, severe muscle metabolic derangement with loss of high-energy phosphate compounds has been observed, indicating a dysfunction or damage of the muscle cells. In six patients operated on for occlusive aortoiliac disease, low-molecular-weight dextran (LMWD) was peroperatively administered for optimal volume loading and prevention of clotting. No heparin was used. Before, during and after the clamping period the central hemodynamics were monitored, and glycogen, glucose, lactate, pyruvate, phosphocreatine (PCr), creatine (Cr), ATP, ADP and AMP content in the thigh muscle were analyzed using enzymatic fluorometric techniques. Even though ischemia developed during the occlusion, no decline in the adenylate (ATP + ADP + AMP) or creatine (PCr + Cr) pools occurred after the clamp was released, and the energy charge of the adenine nucleotides remained unchanged. It is suggested that LMDX prevents rheologic changes impairing the microcirculation during and after the ischemic period, and thereby improves oxygenation of the muscle tissue upon reperfusion.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aged; Aorta; Constriction; Creatine; Dextrans; Energy Metabolism; Glucose; Glycogen; Humans; Ischemia; Lactates; Male; Middle Aged; Muscles; Pyruvates

The extent of binding of glycolytic enzymes to the particulate fraction of homogenates was measured in sheep hind muscles after electrical stimulation. As compared to the control muscles, stimulation led to significant increases in the amount of phosphofructokinase, aldolase and glyceraldehyde-3-phosphate dehydrogenase bound to the particulate fraction. The binding of other glycolytic enzymes was not significantly altered. A servey of different hind limb muscles at variable rates of stimulation revealed that each muscle exhibited its own characteristic response pattern in terms of the level of increased enzyme binding. Generally, an increased stimulation rate led to greater enzyme adsorption. The increase in enzyme binding was rapidly reversible for it was shown that the amount of enzyme bound quickly returned to control values when the muscles were allowed to recover in the live anaesthetised animal following cessation of stimulation. Those muscles which exhibited increased enzyme binding were characterised by a marked loss of glycogen and accumulation of lactate suggesting that accelerated glycolytic flux was a necessary condition for the observation of increased enzyme binding. In support of this, enzyme adsorption was observed to the greatest on stimulation of ischemic muscles, whereas in trained muscles, or muscles with depleted glycogen stores induced by prior adrenalin treatment, the increased enzyme binding response was greatly diminished. It is concluded that the variable binding of key glycolytic enzymes has a role to play in the regulation of glycolytic behaviour in skeletal muscle.

Topics: Animals; Fructose-Bisphosphate Aldolase; Glyceraldehyde-3-Phosphate Dehydrogenases; Glycogen; Glycolysis; Ischemia; Lactates; Lactic Acid; Male; Muscle Contraction; Muscles; Phosphofructokinase-1; Protein Binding; Sheep

A patient with typical features of late onset McArdle's disease is described. During forearm ischemic work test the patient exhibited an exaggerated increase in ammonia release, largely exceeding normal values. It is suggested, that this is due to an activation of the myokinase/myoadenylate deaminase pathway. Besides lack of lactate release increased ammonia release during ischemia may be a typical feature of McArdle's disease.

Topics: Ammonia; Forearm; Glycogen; Glycogen Storage Disease; Glycogen Storage Disease Type V; Humans; Ischemia; Lactates; Lactic Acid; Male; Middle Aged; Physical Exertion

Five young males performed dynamic, submaximal contractions to exhaustion with the quadriceps muscle under arterial occlusion. The work load was 14.7 Watt (W). After 10 min rest with intact arterial circulation, the subjects commenced another bout to exhaustion; this process was repeated until a total of 10--16 bouts had been performed. Muscle biopsies were obtained immediately after the second, fifth, eighth, and last bout as well as 30 min after the last bout. The concentrations of adenosine triphosphate (ATP), creatine phosphate (CP), lactate, and glycogen were measured in each sample and some material underwent histochemical analysis. Muscle lactate was highest following the second work bout [22.9 mmol/kg wet weight (ww)] and gradually declined to 7.0 mmol/kg ww by the end of the last bout. CP level was low in all postexercise samples with the exception of a remarkably high CP (11.7 mmol/kg ww) after the last bout. Glycogen utilization tended to parallel muscle lactate levels, the rate of depletion being most rapid initially. Histochemical staining for glycogen depletion revealed that both type I and II fibres were low in glycogen, although type I was depleted most uniformly. In the first work bouts the high lactate and low CP levels in the total muscle could be responsible for the fatigue; none of these factors seem adequate to explain the development of the fatigue experienced in the later work bouts. It is concluded that muscle fatigue in this type of exercise is not related to substrate depletion or accumulation of metabolites, further that the fibre recruitment pattern is determined by the type and relative severity of performed work rather than local metabolic factors.

Topics: Adenosine Triphosphate; Adult; Glycogen; Humans; Ischemia; Lactates; Male; Muscles; Phosphocreatine; Physical Exertion; Time Factors

A single (40 min) ischemia produces indistinct reversible changes in ultrastructure of cells in the spinal nodes. A repeated ischemia (2 X 40 min) with recirculation produces microstructural lesions both in neural cells and in satellite-cells and capillaries, intensity of the lesions depending on the distance from the ligation (the greatest lesion is situated immediately under the ligation). Most of the neurons are crumped, dark and abundantly vacuolized. In the inferior lumbar and sacral nodes the changes are of moderate character. In all the cases glycogen is accumulating in neurons and satellites with an intact structure. Changes in vessels are more essential after ischemia and recirculation: processes of endothelial cells protrude into the lumen, this, in its turn, results in accumulation of erythrocytes packing tightly the capillaries.

Topics: Animals; Dogs; Endothelium; Female; Ganglia, Spinal; Glycogen; Histocytochemistry; Ischemia; Male; Microscopy, Electron; Neuroglia; Neurons

The hemodynamic changes which occur when clamping and unclamping the aorta during reconstructive surgery might be a threat to the elderly patient with concomitant cardiac disease. In addition, the cross-clamping induces a temporary ischemia of the legs, with severe metabolic derangement after the release of the aortic clamp. We have studied the effect of a intraoperative adrenergic block (phenoxybenzamine plus metoprolol) on the central circulation and the skeletal metabolism in 14 patients undergoing aortic reconstruction to treat occlusive arteriosclerotic disease. Cardiac output, heart rate, arterial and pulmonary artery pressures, and cardiac filling pressures, as well as femoral venous blood flow were studied. Biopsy specimens of the lateral vastus muscle and blood samples from the radial artery and iliac vein were taken before aortic clamping, and before, 30 minutes, four and 16 hours after the aorta was unclamped, as well as five days postoperatively. In addition, intramuscular temperature and pH were measured. Glycogen, glucose, lactate, pyruvate, ATP, ADP, AMP, phosphocreatine (PCr) and creatine (Cr) contents of the muscle and lactate and pyruvate concentrations in iliac venous and radial arterial blood were determined using enzymatic fluorometric techniques. Mean arterial blood pressure (MAP) averaged 80 mmHg before clamping, chiefly because of the low systemic vascular resistance (SVR), and left ventricular stroke work (LVSW) was normal. At clamping MAP, SVR, LVSW, remained unchanged. MAP and LVSW were unaffected even though SVR decreased slightly after the aorta was unclamped and resulted in an increased cardiac output, mainly due to a higher stroke volume. No major change in the pulmonary circulation was observed. During clamping the muscle lactate/pyruvate ratio increased, intramuscular pH and femoral venous blood flow decreased indicating insufficient tissue perfusion. Energy charge (EC), the adenylate (ATP + ADP + AMP) and creatine (PCr + Cr) pools were, however, unchanged. In spite of a restored blood flow to the legs, a severe metabolic derangement of the muscle was observed after declamping, with lowered EC, ATP + ADP + AMP and PCr + Cr indicating cellular damage. No improvement in the condition of the cells was observed 16 hours after operation. In conclusion, we found that by using neurolept anesthesia and an intraoperative adrenergic block in combination with a differentiated fluid therapy the central circulation stabilized and was l

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Aorta; Arteriosclerosis; Constriction; Energy Metabolism; Glucose; Glycogen; Hemodynamics; Humans; Ischemia; Lactates; Muscles; Phosphocreatine; Pyruvates

Topics: Adenine Nucleotides; Animals; Creatine; Energy Metabolism; Epinephrine; Female; Glycogen; Imidazolidines; Ischemia; Kinetics; Mice; Muscles; Phosphates; Phosphocreatine; Rigor Mortis

"Reperfusion syndrome" of the lung may play a role in the pulmonary edema and hemorrhage that occur following pulmonary embolectomy, cardiopulmonary bypass, and shock. Bioenergetic, metabolic, and ultrastructural studies of canine lungs indicate that ventilated lung tissue could tolerate 5 hours of pulmonary arterial occlusion with minimal damage. However, a 24-hour interruption of pulmonary arterial blood flow produced a significant decrease in the ratio of adenosine triphosphate to adenosine disphosphate, and glycogen, and an increase in tissue lactate. Reperfusion of these lungs resulted in even more pronounced biochemical and ultrastructural deterioration, as well as gross pulmonary edema and hemorrhage. The lesion appears to be similar to the reperfusion damage that occurs in other organs, such as the kidney, and the skeletal and cardiac muscles.

Topics: Adenosine Diphosphate; Adenosine Triphosphate; Animals; Constriction; DNA; Dogs; Glycogen; Hemorrhage; Ischemia; Lactates; Lung; Lung Diseases; Pulmonary Artery; Pulmonary Edema; Time Factors

In experiments with dogs, three different methods of inducing a reversible cardiac arrest were compared: (A) the ischemic arrest for 45 min, (B) the cardiac arrest for 90 min due to injection of Cardioplegin according to KIRSCH, and (C) the cardiac arrest for 90 min due to infusion of solution LK 352 according to BRETSCHNEIDER. The body temperature was reduced to 30 degrees C during the period of cardiac arrest. From the alterations in the adenylic acid system of the left ventricular myocardium at the end of the period of myocardial standstill and after 60 min of recovery, it can be deduced that the best myocardial protection is given by method C. Method A has the least effect.

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Aspartic Acid; Dogs; Drug Combinations; Glycogen; Heart; Heart Arrest, Induced; Ischemia; Lactates; Myocardium; Phosphocreatine; Procaine; Sorbitol

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

Acute ischemia was created by placing a tourniquet on the extremity or on a clamp on the kidney limb for a period corresponding to the critical metabolism level in the test tissue study. Restoration of circulation in the ischemic kidney led to the excessive accumulation of glucose high-molecular polymer of the glycogen type. The character of its branching in the molecule determined by the iodine complex spectrum pointed to the changes in the processes of glycogen biosynthesis. Lactate of the ischemic kidney could be used for the glycogenesis requirements. This anomalous glycogen was shown to be actively uptaken by the kidney tissue. Glycogen accumulation in the muscle tissue following acute ischemia failed to exceed the normal level, and its structure was unchanged.

Topics: Acute Disease; Animals; Glycogen; Hindlimb; Ischemia; Kidney; Lactates; Rats

In the atrioventricular system (AVS) consisting of the compact node, the penetrating bundle and the branching bundles of about 250 bovine hearts there were made several studies: 1. In quickly removed and fixed specimens (distal AV-node, penetrating bundle) determination of a metabolic state with respect to glycogen, glucose, lactate, ATP, ADP, AMP, creatinephosphate, total creatine, gluc-6-phosphate, fructose-6-phosphate, fructose-1,6-diphosphate, dihydroxyacetonphosphate and pyruvate. 2. Determination of glycogen contents and glygolytic activity in AVS and its parts for ischemic times up to three hours. 3. The determination of metabolic contents in samples of connective tissue in atrium and ventricle of bovine hearts. The AV-nodes are poor in glycogen comparable with glycogen content of central nervous system and other ganglia. Penetrating bundles of Hiss and branching bundle belong after liver to the glycogen richest parenchyma of animal tissues. Even after ischemia of 3 h only a part of glycogen was recovered as lactate. The greater part of glycogen must be considered as a structural element of Hiss bundle and branching bundles of the ventricles.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Cattle; Connective Tissue; Creatine; Dihydroxyacetone Phosphate; Fructosephosphates; Glucose; Glucosephosphates; Glycogen; Glycolysis; Heart Conduction System; Ischemia; Lactates; Pyruvates

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

Topics: Adenosine Triphosphate; Animals; Brain; Cerebral Cortex; Cyclic AMP; gamma-Aminobutyric Acid; Gerbillinae; Glucose; Glycogen; Ischemia; Lactates; Phosphocreatine; Recurrence

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Brain; Cyclic AMP; Cyclic GMP; Energy Metabolism; Gerbillinae; Glucose; Glycogen; Ischemia; Kinetics; Lactates; Phosphocreatine

In the normal rabbit retina glycogen particles were only observed in the Müller cell. The glycogen was evenly distribution throughout the cytoplasm. The inner retina contained large amounts of Müller cell cytoplasm and consequently possessed substantial quantities of glycogen. The outer retina contained little Müller cell cytoplasm and only small amounts of Glycogen. Following total acute ischaemia induced by high intraocular pressure, the amount of glycogen in the retina fell rapidly so that by 45-60 min of ischaemia it was absent from the Müller cell. In the rabbit, ischaemia preferentially damaged the outer retina and especially the visual cells. This pattern of damage was thought to be a reflection of the amount of glycogen present in the different regions of the retina.

Topics: Acute Disease; Animals; Glycogen; Intraocular Pressure; Ischemia; Rabbits; Retinal Vessels

In newborn rabbits during asphyxia caused by ligature of the trachea circulation was maintained 2-3 times as long as in adult rabbits because in contrast to the adults myocardial energy loss in asphyxia is rather low caused by a small energy consumption for circulatory work. In the cerebral cortex of newborn rabbits glycolysis is able to meet a good part of energy demand, with the energetic situation predominantly depending on glucose supply by maintenance of circulation. Thus in addition sufficient blood glucose levels deliberated from glycogen stores in liver and lung are an important factor for the central nervous revivability. Kidney and skeletal muscle tolerate anaerobic periods for rather long time because of their high glycogen stores and low metabolic activity but do not contribute to glucose supply of other tissues.

Topics: Animals; Animals, Newborn; Asphyxia Neonatorum; Cerebrovascular Circulation; Energy Metabolism; Glycogen; Guinea Pigs; Humans; Infant, Newborn; Ischemia; Lactates; Liver; Medulla Oblongata; Myocardium; Rabbits; Resuscitation

A comparative investigation was made on muscle tissue of man, dog and rat during ischemia of five hours duration. The content of energy rich phosphates was measured. The ATP level decreased after two hours ischemia to 68% in man, to 45% in the dog, and to 23% in the rat. By five hours it had fallen further to 25% in man, 9% in the dog and only 1% in the rat. It is concluded that human muscle has a higher tolerance to ischemia.

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Creatine; Dogs; Energy Metabolism; Glycogen; Humans; Ischemia; Lactates; Muscles; Phosphocreatine; Rats; Time Factors

The carbohydrate metabolism in hypothyroid patients was investigated. After an overnight fast, the blood glucose level was 24% lower and the blood lactate level was 35% lower in the untreated hypothyroid patients than that observed in the treated hypothyroid patients or in the normal subjects. There was no difference in the blood alanine or plasma free fatty acid values between the subject groups. Skeletal muscle biopsied from two hypothyroid patients with marked myopathy showed normal glycogen content, 0.83%-0.86% (normal 1.06%), but reduced activity of acid maltase, 32-50 nmoles/min/g (normal 97). Forearm ischemic stimulation applied to hypothyroid patients failed to elevate the level of lactate. The results are compatible with impaired glycogenolysis from the skeletal muscle, which may be a contributory factor in the myopathy in hypothyroidism.

Topics: Adolescent; Adult; Alanine; Blood Glucose; Creatine Kinase; Fatty Acids, Nonesterified; Female; Glycogen; Humans; Hypothyroidism; Ischemia; Lactates; Male; Middle Aged; Muscles; Muscular Diseases; Reference Values; Thyrotropin

Topics: Adenosine Triphosphate; Animals; Brain; Cyclic AMP; Gerbillinae; Glucose; Glucosephosphates; Glycogen; Ischemia; Lactates; Phosphocreatine; Uridine Diphosphate Glucose

Topics: Acid Phosphatase; Adult; Aged; Alkaline Phosphatase; Brain; Cerebral Hemorrhage; Cerebrovascular Disorders; Electron Transport Complex IV; Female; Glycogen; Histocytochemistry; Humans; Ischemia; Ischemic Attack, Transient; Leukocytes; Male; Middle Aged; Peroxidases

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

The glycogen content in the individual eye tissues is strongly correlated to blood supply. Our investigations on the retina of bovines, which have not been fully evaluated, show that the time interval between interruption of blood supply and preparation of the retina is of special importance. Pressure ischemia affects a decrease in glycogen content in the retina and vitreous of rabbits, which is, however, less distinct in the vitreous. Decrease of glycogen with ischemia also takes place in the cornea and, to a lesser degree, in iris and choroid. In contrast, there is no decrease in the glycogen content of the lens. Changes in glycogen content of the rabbit retina after ligation of the A. carotis communis is less distinct than with pressure ischemia. In the vitreous, changes in glycogen content could not be observed. Values measured in both tissues of the ligated eye decrease with additional pressure ischemia.

Topics: Animals; Carotid Arteries; Cattle; Choroid; Cornea; Glycogen; Intraocular Pressure; Iris; Ischemia; Lens, Crystalline; Retina; Retinal Vessels; Time Factors; Vitreous Body

Topics: 1,4-alpha-Glucan Branching Enzyme; Adenine Nucleotides; Adrenal Cortex Hormones; Animals; Blood Glucose; Body Temperature Regulation; Brain; Brain Diseases; Brain Injuries; Catecholamines; Central Nervous System; Chemical Phenomena; Chemistry, Physical; Glycogen; Glycogen Synthase; Histocytochemistry; Histological Techniques; Humans; Hypoxia, Brain; Insulin; Ischemia; Nerve Degeneration; Phenobarbital; Phosphorylases; Radiation Effects; Radiation, Ionizing; Rats; Retina

Topics: Acute Disease; Animals; Chemical Phenomena; Chemistry; Dogs; Female; Glycogen; Intestinal Mucosa; Intestine, Small; Iodine; Ischemia; Kidney Cortex; Male; Muscles

The metabolic states of various tissues of newborn rabbits were studied before and after periods of ischemia of 5-40 min. The contents of substances of the energy distributing adenylic acid-creatine phosphate system as well as glycogen, glucose and lactate were determined and the results are discussed in comparison with the well-known values from ischemic tissues of adult rabbits. The preservation of high energy phosphates as well as the rate of glycolytic energy production during the course of ischemia was quite identical in the myocardium of newborns and adults in contrast to the different ability of newborn and adult rabbits to maintain circulation in anaerobic conditions. In the central nervous system the ATP contents decreased to very low levels within a few minutes in both groups although the glycolytic energy production was rather different. But the larger amounts of adenine nucleotides present in the newborns at any time of ischemia indicate a better chance of postischemic recovery. In the livers and the kidneys of the newborns higher rates of glycolytic energy production led to better preservation of the energy-rich substances while in skeletal muscle and the lung only slight differences occurred between newborns and adults.

Topics: Adenine Nucleotides; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Animals, Newborn; Bone and Bones; Brain; Energy Metabolism; Glucose; Glycogen; Ischemia; Kidney; Lactates; Liver; Myocardium; Phosphocreatine; Rabbits

A cerebral ischemia was produced by unilateral ligation of the common carotid artery in the neck of Mongolian gerbils (Meriones unguiculatus), which are frequently characterized by deficiencies in the circulus of Willis. Concentrations of glucose, lactate, pyruvate and glycogen were measured in the hemisphere on the side of occlusion and in the contralateral control hemisphere of animals sacrificed after 5, 15 and 30 min, as well as after 1,3,5 and 9 hrs of carotid clamping. Significant decrease of glucose, and increase in lactate and pyruvate concentration were found in the hemisphere ipsilateral to occlusion; the extent of the changes was proportional to the duration of the ischemia. After an initial fall, an increase in the glycogen content occurred in the later stages of ischemia. Glycogen, glucose, lactate and pyruvate were determined also at 1, 5, 20 hrs and 1 week intervals following release of an occlusion lasting for 1 hr. Return to normal values of glucose and pyruvate was seen at 1 hr after release. The lactate and glycogen levels were significantly raised on the occluded side after 20 hrs release. An increased level of glycogen was observed as long as 1 week after a 1-hr carotid occlusion.

Topics: Animals; Brain; Carbohydrate Metabolism; Carotid Arteries; Cerebrovascular Disorders; Gerbillinae; Glucose; Glycogen; Ischemia; Lactates; Ligation; Pyruvates; Time Factors

Topics: Adenosine Triphosphate; Amines; Animals; Brain; Brain Chemistry; Cerebellum; Energy Metabolism; Fructosephosphates; Gluconates; Glucose; Glucosephosphates; Glycogen; Hypoxia, Brain; Ischemia; Isocitrates; Lactates; Malates; Mice; NAD; NADP; Niacinamide; Phosphocreatine; Ribose

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

Acute gastric erosions following hemorrhagic shock (stress ulceration) have been attributed to gastric hyperacidity, altered gastric secretion of mucus and an abnormal permeability of the gastric mucosa to H(+). This report aims at presenting evidence supporting an alternate hypothesis: the event linking shock-induced gastric mucosal ischemia to mucosal necrosis is a deficit in gastric mucosal energy metabolism. Our experimental procedure consisted of harvesting the stomachs of rats and rabbits by "stop-freeze" (liquid N(2)) at different intervals after the induction of hemorrhagic shock. Levels of adenosine-phosphates and of glycolytic intermediates in gastric mucosa were measured. We studied the changes in the levels of these substrates produced by shock as well as by factors capable, when combined with shock, of rendering the gastric mucosa more vulnerable to stress ulceration. The influence of shock and of these modifying factors were evaluated by comparison with data from appropriately designed control experiments. In parallel experiments we examined the frequency of stress ulceration (gross and microscopic) under these same standard conditions. There have emerged from these studies a number of observations all based upon data with the highest statistical significance. The data are consonant with the hypothesis stated above: an energy deficit severe enough to cause cellular necrosis is the event linking shock-induced gastric mucosal ischemia and stress ulceration.

Topics: Adenine Nucleotides; Adenosine Triphosphatases; Animals; Energy Metabolism; Fasting; Gastric Mucosa; Glucosephosphates; Glycogen; Ischemia; Lactates; Liver; Male; Muscles; Peptic Ulcer; Phosphocreatine; Pyruvates; Rabbits; Rats; Shock, Hemorrhagic; Taurocholic Acid

Topics: Adenosine Triphosphate; Animals; Biopsy; Glucose; Glycogen; Guinea Pigs; Ischemia; Phosphorylases; Skin; Time Factors; Wound Healing

Topics: Adenine Nucleotides; Animals; Dogs; Energy Metabolism; Female; Glycogen; Intestinal Mucosa; Intestine, Small; Ischemia; Lactates; Male; Regional Blood Flow; Time Factors; Transplantation, Homologous

Topics: Acid-Base Equilibrium; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Bicarbonates; Blood Glucose; Glycogen; Humans; Ischemia; Lactates; Muscles; Pyruvates; Time Factors; Tourniquets

Topics: Adult; Alanine Transaminase; Aspartate Aminotransferases; Creatine Kinase; Fructose-Bisphosphate Aldolase; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Humans; Ischemia; Lactates; Male; Muscles; Muscular Diseases; Phosphorylase Kinase; Physical Exertion; Pyruvates; Syndrome

Topics: Animals; Atrioventricular Node; Cattle; Glycogen; Heart Conduction System; Histological Techniques; Ischemia; Lactates

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Anaerobiosis; Animals; Energy Metabolism; Gastric Mucosa; Glucosephosphates; Glycogen; Glycolysis; Ischemia; Lactates; Liver; Male; Muscles; Necrosis; Pyruvates; Rats; Shock, Hemorrhagic; Stomach Ulcer; Stress, Physiological

Topics: Acidosis; Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Blood Pressure; Body Temperature; Brain; Creatine; Energy Metabolism; Glucosephosphates; Glycogen; Hydrogen-Ion Concentration; Hyperglycemia; Hypoglycemia; Ischemia; Lactates; Phosphocreatine; Pyruvates; Rats

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: Adenosine Triphosphate; Animals; Creatine; Epithelial Cells; Glucose; Glycogen; Guinea Pigs; Ischemia; Lactates; Mice; Microscopy, Phase-Contrast; Nerve Tissue; Organ of Corti; Phosphates; Vestibule, Labyrinth

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Animals; Blood Glucose; Blood Pressure; Creatine; Glycogen; Hindlimb; Ischemia; Lactates; Male; Muscles; Necrosis; Phosphocreatine; Rats; Time Factors; Tourniquets

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: Animals; Coronary Circulation; Disease Models, Animal; Dogs; Extracorporeal Circulation; Glycogen; Heart Arrest, Induced; Heart Diseases; Heart Ventricles; Histocytochemistry; Ischemia; Magnesium Sulfate; Microscopy, Electron; Myocardium; Perfusion; Postoperative Complications; Time Factors

Topics: Adenosine Triphosphate; Animals; Connective Tissue; Epithelium; Glycogen; Guinea Pigs; Ischemia; Regeneration; Skin; Wound Healing

Topics: Cell Count; Cell Differentiation; Chromatin; Female; Gestational Age; Glycogen; Golgi Apparatus; Histocytochemistry; Humans; Ischemia; Microscopy, Electron; Mitochondria; Necrosis; Placenta; Placenta Diseases; Pregnancy; Regeneration; Rh-Hr Blood-Group System; Staining and Labeling

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; Argon; Cochlea; Cochlear Nerve; Disease Models, Animal; Ear, Inner; Electrophysiology; Freeze Drying; Glucose; Glycogen; Guinea Pigs; Ischemia; Labyrinth Diseases; Labyrinthine Fluids; Lactates; Organ of Corti; Phosphocreatine; Time Factors; Vestibule, Labyrinth

Topics: Age Factors; Animals; Animals, Newborn; Blood Glucose; Body Temperature; Brain; Brain Chemistry; Cerebellum; Chickens; Circadian Rhythm; Diencephalon; Female; Glycogen; Hyperglycemia; Hypoglycemia; Ischemia; Male; Medulla Oblongata; Motor Activity; Temperature; Time Factors

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: Acetoacetates; Acetyl Coenzyme A; Animals; Blood Glucose; Burns; Carbon Radioisotopes; Fatty Acids, Nonesterified; Glutamates; Glycogen; Hindlimb; Hydroxybutyrates; Ischemia; Lactates; Liver; Mitochondria, Liver; Pyruvates; Rats; Wounds and Injuries

Topics: Adenine Nucleotides; Adenosine Monophosphate; Adenosine Triphosphate; Aerobiosis; Anaerobiosis; Animals; Dogs; Glucose; Glycogen; Ischemia; Kidney; Lactates; Oxygen; Phosphocreatine; Tissue Preservation

Topics: Adenosine Triphosphate; Animals; Brain; Cerebral Cortex; Chick Embryo; Creatine; Electroencephalography; Glucose; Glucosephosphates; Glycogen; Glycolysis; Ischemia; Lactates; Mice; Phosphocreatine; Pyruvates

1. Experimental cardiac arrhythmias were produced in dogs anaesthetized with pentobarbitone. Ventricular arrhythmias were induced by strophanthin-K, light petroleum plus adrenaline or coronary ligation procedures. Atrial flutter was induced by an injury-stimulation technique. The acetylcholine and glycogen concentrations of the atria and ventricles were estimated.2. Physostigmine pretreatment (0.1 mg/kg) significantly reduced the incidence of ventricular arrhythmias after myocardial ischaemia but had no effect on any of the other arrhythmias.3. Physostigmine markedly increased the acetylcholine concentrations of atria and ventricles in control dogs, to nearly the same extent. Physostigmine had no effect on ventricular acetylcholine concentrations in dogs treated with strophanthin-K and light petroleum plus adrenaline but in the coronary ligation group it caused a significant increase in the acetylcholine concentrations of both atria and ventricles, and of atrial acetylcholine only in the injury-stimulation group.4. All the arrhythmias produced marked glycogenolysis of both the atria and the ventricles, to nearly the same extent. Although physostigmine produced marked glycogenolysis in the control dogs it significantly inhibited cardiac glycogenolysis after light petroleum plus adrenaline, atrial glycogenolysis after strophanthin-K-induced arrhythmias and ventricular glycogenolysis after myocardial ischaemia.5. There appears to be a possible correlation between the increase in the acetylcholine concentration of the ventricles and anti-arrhythmic actions of physostigmine, but there is a less clear correlation between changes in the glycogen concentration of ventricles and the anti-arrhythmic action.

Topics: Acetylcholine; Animals; Arrhythmias, Cardiac; Atrial Flutter; Coronary Vessels; Dogs; Female; Glycogen; Heart Atria; Heart Ventricles; Ischemia; Ligation; Male; Petroleum; Physostigmine; Strophanthins; Wounds and Injuries

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: Adenine Nucleotides; Age Factors; Animals; Animals, Newborn; Cerebral Cortex; Cold Temperature; Glycogen; Glycolysis; Ischemia; Kidney; Medulla Oblongata; Myocardium; Rabbits; Time Factors

Topics: Animals; Cats; Female; Glucosyltransferases; Glycogen; Histocytochemistry; Ischemia; Male; Microscopy, Electron; Motor Neurons; Neuroglia; Phosphorylases; Spinal Cord; Time Factors

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

Topics: Acid Phosphatase; Animals; Coronary Vessels; Dogs; Female; Glycogen; Hydrogen-Ion Concentration; In Vitro Techniques; Ischemia; Ligation; Lysosomes; Male; Muscles; Myocardial Infarction; Papillary Muscles; Potassium; Time Factors

Topics: Aged; Arterial Occlusive Diseases; Carbon; Carbon Dioxide; Female; Glucose; Glycogen; Humans; Intermittent Claudication; Ischemia; Lactates; Leg; Lipids; Male; Middle Aged; Muscles; Succinate Dehydrogenase

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

Topics: Animals; Anterior Chamber; Aqueous Humor; Ciliary Body; Cornea; Electrocoagulation; Eye; Eye Diseases; Glucose; Glycogen; Iris; Ischemia; Lactates; Lens, Crystalline; Necrosis; Rabbits; Water

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Arteries; Blood Pressure; Body Temperature; Carbon Dioxide; Cardiac Surgical Procedures; Extracorporeal Circulation; Glycogen; Heart; Heart Arrest; Heart Arrest, Induced; Heart-Lung Machine; Hydrogen-Ion Concentration; Hypothermia, Induced; Ischemia; Lactates; Methods; Myocardium; Phosphates; Phosphocreatine; Potassium; Rabbits; Respiration, Artificial; Resuscitation; Time Factors

Topics: Animals; Coronary Vessels; Culture Techniques; Diagnosis, Differential; Diffusion; Glucosyltransferases; Glycogen; Histocytochemistry; Ischemia; Isoenzymes; Ligation; Myocardial Infarction; Myocardium; Perfusion; Phosphorylases; Rats; Time Factors

Topics: Animals; Brain; Brain Chemistry; Cerebrovascular Disorders; Female; Glucosyltransferases; Glycogen; Ischemia; Male; Phosphorylases; Rats; Time Factors

Topics: Adenosine Triphosphate; Anesthesia; Animals; Brain; Creatine; Electric Stimulation; Glucose; Glycogen; Ischemia; Lactates; Male; Mice; Neurons; Phenobarbital; Spinal Cord

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

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

Topics: Adenosine Triphosphatases; Adenosine Triphosphate; Animals; Biological Transport, Active; Cerebellar Cortex; Cerebellum; Cochlea; Fructosephosphates; Glycogen; Glycolysis; Haplorhini; In Vitro Techniques; Ischemia; Isoenzymes; L-Lactate Dehydrogenase; Mechanoreceptors; Organ of Corti; Phosphorylases; Photoreceptor Cells; Rabbits; Retina

Topics: Adenosine Triphosphate; Animals; Fluorometry; Glucose; Glycogen; Ischemia; Lactates; Male; Muscle Denervation; Muscles; Oxygen Consumption; Phosphates; Phosphocreatine; Rats

Topics: Adenosine Triphosphate; Animals; Cadmium; Capillary Permeability; Fructose; Glucose; Glycogen; Injections, Subcutaneous; Ischemia; Lactates; Male; Rats; Testis

Topics: Animals; Blood Glucose; Brain; Brain Chemistry; Cerebrovascular Circulation; Cyanides; Glucosyltransferases; Glycogen; Glycolysis; Histocytochemistry; Hypoxia, Brain; Ischemia; Male; Neuroglia; Rats

Topics: Animals; Blood Vessels; Capillaries; Collateral Circulation; Dogs; Glycogen; Humans; Iliac Vein; Ischemia; Methods; Muscle Denervation; Muscles; Pelvis; Rectum; Time Factors

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Blood Glucose; Brain; Cerebrovascular Disorders; Glucose; Glycogen; Hexosephosphates; Hypoxia, Brain; Ischemia; Lactates; Mice; Phosphocreatine

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Brain; Cerebellum; Cerebral Cortex; Creatine; Diencephalon; Glucose; Glycogen; Glycolysis; Ischemia; Medulla Oblongata; Mesencephalon; Phosphocreatine; Rabbits

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Blood Pressure; Brain; Cerebral Cortex; Diencephalon; Electroencephalography; Glucose; Glycogen; Ischemia; Lactates; Medulla Oblongata; Mesencephalon; Phosphocreatine; Rabbits; Time Factors

Topics: Adenine Nucleotides; Adrenalectomy; Animals; Barium; Brain Chemistry; Chemical Precipitation; Chromatography, Thin Layer; Cyclic AMP; Diaphragm; Dogs; Epinephrine; Fluorometry; Glucosyltransferases; Glycogen; Hexokinase; Hydrocortisone; Infusions, Parenteral; Ischemia; Kidney; Kinetics; Liver; Methods; Microchemistry; Muscles; Phosphoric Monoester Hydrolases; Phosphotransferases; Pyruvate Kinase; Rabbits; Rats; Tritium; Water-Electrolyte Balance

Topics: Adenosine Triphosphate; Animals; Butyrates; Carbutamide; Cyclic AMP; Diazoxide; Epinephrine; Glucagon; Glucose; Glycogen; Histocytochemistry; Hypoglycemic Agents; In Vitro Techniques; Insulin; Insulin Secretion; Ischemia; Islets of Langerhans; Mice; Obesity; Pancreatic Diseases; Sulfonamides; Theophylline

Topics: Animals; Cyclic AMP; Fluorometry; Glucagon; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glycogen; Hexokinase; Hyperglycemia; Ischemia; Islets of Langerhans; Mice; NADP; Obesity; Phosphoglucomutase

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

Topics: Animals; Autolysis; Dogs; Glycogen; Ischemia; Lactates; Microscopy, Electron; Mitochondria, Muscle; Myocardium; Oxygen Consumption; Pyruvates; Succinates

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

Topics: Adenosine Triphosphate; Animals; Animals, Newborn; Brain; Brain Chemistry; Glucose; Glycogen; Glycolysis; Hexosephosphates; Ischemia; Lactates; Methods; Mice; Phosphocreatine

Topics: Adenine Nucleotides; Adenosine Triphosphate; Anesthesia; Animals; Brain; Brain Chemistry; Glucose; Glycogen; Hyperbaric Oxygenation; Ischemia; Lactates; Oxygen Consumption; Phosphocreatine; Rats

Topics: Antithyroid Agents; Creatine Kinase; Fructose; Glucose; Glycogen; Humans; Hyperthyroidism; In Vitro Techniques; Ischemia; Lactates; Male; Middle Aged; Muscle Cramp; Muscles; Propylthiouracil

Topics: Adenosine Triphosphate; Animals; Chlorothiazide; Diabetes Mellitus, Experimental; Glucose; Glycogen; Hexosephosphates; Insulin; Ischemia; Kidney; Lactates; Male; Organomercury Compounds; Phlorhizin; Phosphocreatine; Rats; Starvation

Topics: Animals; Collateral Circulation; Glycogen; Hindlimb; Histocytochemistry; Ischemia; Methods; Muscles; Rabbits; Succinate Dehydrogenase; Time Factors

Topics: Adenine Nucleotides; Adenosine Triphosphate; Brain; Brain Neoplasms; Fluorometry; Frontal Lobe; Glioma; Glucose; Glycogen; Glycolysis; Hexoses; Humans; In Vitro Techniques; Ischemia; Lactates; Phosphocreatine; Spectrophotometry; Tissue Extracts

Topics: Adenosine Triphosphate; Animals; Brain Neoplasms; Glucose; Glycogen; Ischemia; Lactates; Mice; Phosphorus

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

Topics: Adenosine Triphosphate; Animals; Brain Neoplasms; Creatine Kinase; Glioblastoma; Glucose; Glucosephosphate Dehydrogenase; Glucosyltransferases; Glutamate Dehydrogenase; Glycogen; Glycolysis; Hexokinase; Histocytochemistry; Ischemia; Lactates; Mice; NAD; NADP; Neoplasms, Experimental; Phosphates; Phosphocreatine; Phosphoglucomutase; Phosphogluconate Dehydrogenase

Topics: Adult; Electric Stimulation; Electromyography; Glucosyltransferases; Glycogen; Glycogen Storage Disease; Histocytochemistry; Humans; Ischemia; Lactates; Male; Microscopy, Electron; Muscle Contraction; Muscles; Muscular Diseases; Myofibrils; Neural Conduction; Pyruvates

Topics: Adenine Nucleotides; Adenosine Triphosphate; Animals; Cats; Cholecystokinin; Glucose; Glycogen; Ischemia; Lactates; Pancreas; Pancreatic Juice; Phosphocreatine; RNA; Secretin

Topics: Animals; Calcium; Coronary Disease; Dogs; Electrons; Glycogen; Histocytochemistry; Ischemia; Microscopy; Microscopy, Electron; Mitochondria; Pathology; Research

Topics: Adenosine Triphosphate; Brain Neoplasms; Coenzymes; Glucose; Glycogen; Glycolysis; Hexosephosphates; Ischemia; Lactates; Phosphates; Phosphocreatine; Research

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: Adenosine Triphosphatases; Carbohydrate Metabolism; Coronary Disease; Glycogen; Ischemia; Metabolism; Muscle Proteins; Myocardium; Proteins; Research

Topics: Adenine Nucleotides; Animals; Cardiac Surgical Procedures; Citrates; Citric Acid; Coenzymes; Dogs; Electrocardiography; Glycogen; Heart Arrest; Heart Arrest, Induced; Ischemia; Lactates; Myocardial Infarction; Phosphates; Rabbits; Research; Thoracic Surgery

Topics: Carotid Arteries; Cerebral Cortex; Citrates; Citric Acid Cycle; Depression; Electroencephalography; Glucose; Glycogen; Ischemia; Ketoglutaric Acids; Lactates; Pharmacology; Physiology; Potassium; Pyruvates; Rats; Research; Sodium Chloride; Strychnine

Topics: Adenosine Triphosphate; Adrenocorticotropic Hormone; Catecholamines; Glucose-6-Phosphatase; Glycogen; Hematocrit; Humans; Ischemia; Lactates; Metabolism; NAD; NADP; Proteins; Pyruvates; Shock; Uric Acid

Topics: Adenosine Triphosphate; Animals; Coenzymes; Energy Metabolism; Glycogen; Ischemia; Lactates; Muscle, Skeletal; Muscles; Phosphorus; Rabbits

Topics: Glycogen; Glycogenolysis; Ischemia; Kidney; Ligation

Topics: Animals; Blood Glucose; Extremities; Glycogen; Glycogenolysis; Ischemia; Rats; Shock

Topics: Electrolytes; Glycogen; Glycogenolysis; Injections, Intra-Arterial; Ischemia; Microspheres; Muscles