glycogen and Shock--Septic

Despite the remarkable progress in intensive care medicine, sepsis and shock continue to be major clinical problems in intensive care units. Septic shock may be associated with a toxic state initiated by the stimulation of monocytes by bacterial toxins such as endotoxin, which is released into the bloodstream. This study describes the role of oxidative stress in endotoxin-induced metabolic disorders. We demonstrate that endotoxin injection results in lipid peroxide formation and membrane injury in experimental animals, causing decreased levels of free radical scavengers or quenchers. Interestingly, it was also suggested that tumor necrosis factor (TNF)-induced oxidative stress occurs as a result of bacterial or endotoxin translocation under conditions of reduced reticuloendothelial system function in various disease states. In addition, we suggest that intracellular Ca2+, Zn2+, or selenium levels may participate, at least in part, in the oxidative stress during endotoxemia. On the other hand, it is also suggested that the extent of endotoxin-induced nitric oxide (NO) formation may be due, at least in part, to a change in heme metabolic regulation during endotoxemia. However, in our experimental model, NO is not crucial for lipid peroxide formation during endotoxemia. Sho-saiko-to is one of the most frequently prescribed Kampo medicines and has primarily been used to treat chronic hepatitis. We report that Sho-saiko-to decreases the rh TNF-induced lethality in galactosamine-hypersensitized mice and protects mice against oxygen toxicity and Ca2+ overload in the cytoplasm or mitochondria during endotoxemia. We further suggest that Sho-saiko-to shows a suppressive effect on NO generation in macrophages stimulated with endotoxin and that it may be useful in improving endotoxin shock symptoms.

Topics: Animals; Calcium; Cytokines; Drugs, Chinese Herbal; Endotoxemia; Endotoxins; Free Radicals; Glycogen; Humans; Lipoproteins; Mice; Mononuclear Phagocyte System; Nitric Oxide; Oxidative Stress; Phytotherapy; Shock, Septic; Trace Elements

Topics: Glycogen; Humans; Kidney Diseases; Myocardium; Shock, Septic; Streptococcal Infections

Myocardial hibernation is an adaptive response to ischemia and hypoxia. Hibernating cardiomyocytes are reversibly hypocontractile and demonstrate characteristic metabolic and ultrastructural changes. These include a switch in primary substrate utilization from fatty acids to glucose, up-regulation of the myocardial specific glucose transporters (GLUT1 and GLUT4), and glycogen deposition within and between cardiomyocytes. We hypothesized that myocardial hibernation may underlie sepsis-associated myocardial depression.. Prospective observational study aimed at identifying the characteristic changes of hibernation in the septic heart.. University hospital-based laboratory.. Forty-three C57Bl6 male mice.. Mice underwent cecal ligation and double puncture, sham operation, or no operation and were evaluated 48 hrs after the procedure.. Using novel, clinically relevant technology such as magnetic resonance imaging, positron emission tomography, and single photon emission computed tomography imaging, we found septic mice to have diminished cardiac performance, increased myocardial glucose uptake, increased steady-state levels of myocardial GLUT4, and increased deposits of glycogen, recapitulating the changes during hibernation. Importantly, these changes occurred in the setting of preserved arterial oxygen tension and myocardial perfusion.. Sepsis-associated cardiac dysfunction may reflect hibernation. Furthermore, such down-regulation of cellular function may underlie sepsis-induced dysfunction in other organ systems.

Topics: Animals; Blood Glucose; Energy Metabolism; Fatty Acids; Glucose Transporter Type 1; Glucose Transporter Type 4; Glycogen; Hemodynamics; Male; Mice; Mice, Inbred C57BL; Myocardial Contraction; Myocardial Stunning; Myocytes, Cardiac; Shock, Septic; Up-Regulation

The quantitative histochemical changes of glycogen SDH in the adrenal gland of endotoxic-shocked rat induced by electro-acupuncture were observed in this paper. The result indicates that electro-acupuncture at "Ren Zhong" or "Zusali" of endotoxic shocked animal might improve the function of adrenal cortex and achieve recovery in certain extent.

Topics: Adrenal Glands; Animals; Electroacupuncture; Glycogen; Male; Rats; Shock, Septic; Succinate Dehydrogenase

The importance of the adrenal gland in the 10 day old (10 d) rats' glucoregulatory response to endotoxin (ETX) was investigated. Plasma glucose, lactate, and liver glycogen were measured at 0, 2, 3, and 4 h after ETX to 10 d adrenalectomized (ADRNX), adrenal demedullated (MEDX), and sham-operated (SHAM) rats. At 24 h after ETX, mortality in the ADRNX group was a striking 86% compared with 34% and 36% in intact and SHAM groups, respectively. Mortality in MEDX rats (47%) did not differ from control groups. Although MEDX exacerbated hypoglycemia at 3 and 4 h after ETX (p < or = .05), ADRNX produced severe hypoglycemia by 2 h after ETX. Lactacidemia occurred earlier and was greater in ADRNX rats than in MEDX and SHAM rats. Unlike MEDX, ADRNX significantly decreased liver glycogen and ETX rapidly depleted the remaining glycogen by 2 h after injection. These results demonstrate the greater importance of the adrenal cortex relative to the adrenal medulla in the 10 d rats' defense against ETX-induced hypoglycemia, hyperlactacidemia, and lethality.

Topics: Adrenal Cortex; Adrenal Medulla; Adrenalectomy; Animals; Animals, Newborn; Blood Glucose; Endotoxins; Glucose; Glycogen; Lactates; Lactic Acid; Liver; Rats; Rats, Sprague-Dawley; Shock, Septic; Survival Analysis

Gram-negative sepsis/septic shock in the newborn continues to be a major medical problem, causing high mortality. Hyperglycemia followed by hypoglycemia is a common symptom in endotoxic shock. However, the mechanism of newborn glucoregulatory response to endotoxin has not been well understood. Paradoxically, monocyte-phagocytes can contribute to shock by overwhelming secretion of cytokines and also host defense by detoxifying endotoxin. Since monocyte-phagocyte function is immature in the newborn, this study was performed to evaluate Kupffer cell's role in liver glycogenolysis during endotoxic shock. Endotoxin (LPS) induced hyperglycemia in 10-day-old rats, and increased net glucose output in the isolated perfused liver. 1) Cytarabine decreased Kupffer cell function (decreased hepatic colloid carbon uptake) and blunted LPS-increased liver net glucose output in the Cytarabine + LPS-treated group (104 +/- 4 vs. 146 +/- 3 micrograms/min/g wet liver in the LPS-treated group: P < .001). 2) Indomethacin (IND) suppressed LPS-induced liver net glucose output in the LPS + IND-treated group (133 +/- 5 vs. 146 +/- 3 micrograms/min/g wet liver, P < .05). Thus, prostaglandins were suggested to contribute to glycogenolysis in the 10-day-old rat liver. 3) Phorbol 12-myristate 13-acetate (PMA) increased liver net glucose output (166 +/- 4 micrograms/min/g wet liver), and H-7, a protein kinase C inhibitor, blunted PMA-induced liver glucose output (140 +/- 2 micrograms/min/g wet liver, P < .05). H-7 enhanced LPS-induced liver net glucose output (196 +/- 9 micrograms/min/g wet liver, P < .01). Therefore, protein kinase C may not be the dominant cell signaling system for LPS stimulation in suckling rat Kupffer cells.

Topics: 1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; Animals; Animals, Newborn; Cytarabine; Disease Models, Animal; Glycogen; Indomethacin; Isoquinolines; Kupffer Cells; Lipopolysaccharides; Liver; Piperazines; Rats; Rats, Sprague-Dawley; Shock, Septic; Tetradecanoylphorbol Acetate

Diaphragmatic function was investigated in mechanically ventilated rats during endotoxic shock (group E, n = 18) and after saline solution injection (group C, n = 8). Endotoxic shock was produced by a 1-min injection of Escherichia coli endotoxin (10 mg/kg iv) suspended in saline. Diaphragmatic strength was assessed before (T0) and 15 (T15) and 60 (T60) min after injection by measuring transdiaphragmatic pressure (Pdi) generated during bilateral phrenic stimulation at 0.5, 10, 20, 30, 50, and 100 Hz. Diaphragmatic neuromuscular transmission was assessed by measuring the integrated electrical activity of the diaphragm. Diaphragmatic endurance was assessed 75 min after injection from the rate of Pdi decline after a 30-s continuous 10-Hz phrenic stimulation. In 16 additional animals, diaphragmatic glycogen content was determined 60 min after inoculation with endotoxin (n = 8) or 0.9% sodium chloride solution (n = 8). Diaphragmatic resting membrane potential (Em) was measured in 16 additional animals 60 min after endotoxin (n = 8) or saline injection (n = 8). Mean blood pressure decreased from 74 +/- 3 to 53 +/- 6 mmHg at T60 in group E, whereas it was maintained in group C. At T60 Pdi was decreased in group E for frequencies of 50 and 100 Hz and was associated with a decreased diaphragmatic electromyographic activity of 25.3 +/- 2.5 and 26.5 +/- 5.2% for 50- and 100-Hz stimulations, respectively, in comparison with T0 values.(ABSTRACT TRUNCATED AT 250 WORDS)

Topics: Animals; Diaphragm; Electric Stimulation; Glycogen; Membrane Potentials; Muscle Contraction; Neuromuscular Junction; Physical Endurance; Rats; Rats, Inbred Strains; Respiration, Artificial; Shock, Septic; Synaptic Transmission

Neonatal sepsis is a significant health problem. However, to our knowledge, the temporal substrates and insulin response to endotoxin have not been characterized in the young animal to guide the investigations of glucoregulation in septic shock in the newborn. We characterized the temporal response to endotoxin in the developing rat. Sprague-Dawley rats were given intraperitoneal Salmonella enteritidis endotoxin in high and low lethal doses to zero, ten and 28 day old rats. Mortality, temporal glucose, lactate, hepatic glycogen and insulin were monitored. Mortality experiments show the ten day old rat is 300 times as sensitive to endotoxin as the 28 day old rat. Plasma glucose concentration increased in the high mortality groups by 120 minutes in the zero and ten day old rats (102 +/- 4 milligrams per deciliter, 119 +/- 6 milligrams per deciliter, respectively, and by 60 minutes in the 28 day old rats (223 +/- 12 milligrams per deciliter). The plasma glucose level decreased to 52 +/- 3 milligrams per deciliter by 240 minutes in the ten day old and by 180 minutes to 99 +/- 8 milligrams per deciliter in the 28 day high mortality groups. Peak lactic acid levels in the high lethality groups were zero day 2.8 +/- 0.2 millimoles per liter in zero day old rats, 3.3 +/- 0.2 millimoles per liter in 28 day old rats. Glycogen in the liver decreased rapidly by 120 minutes in all age groups. Plasma insulin concentration did not elevate significantly in zero and ten day old rats. In the 28 day old rat, insulin concentration increased by 120 minutes to 52 +/- 17 microunits per milliliter. Insulin glucose ratios were also elevated in the 28 day old endotoxin treated rat, indicating hyperinsulinemia. Thus, temporal substrates and insulin responses to endotoxin differ with animal age.

Topics: Age Factors; Animals; Blood Glucose; Disease Models, Animal; Female; Glycogen; Insulin; Lactates; Liver; Monitoring, Physiologic; Polysaccharides, Bacterial; Pregnancy; Rats; Rats, Inbred Strains; Salmonella enteritidis; Shock, Septic; Time Factors

A rat model was used to study the effects of endotoxemic shock in vivo on diaphragmatic tension generation and diaphragmatic metabolism in vitro. Animals were injected with E. coli lipopolysaccharide (30 mg/kg) and killed at fixed times after injection. The hemidiaphragms were isolated in an organ bath, and tension generation was measured during electrical stimulation of the phrenic nerve or diaphragmatic muscle. Diaphragmatic oxygen consumption was measured in vitro during rest and during in vivo stimulation. Adenosine triphosphate and glycogen concentrations were measured in vivo before the animals were killed and in vitro. Tension generation was reduced in a time-dependent fashion after endotoxin at all stimulation frequencies. Both contractile fatigue and transmission fatigue were present. Glycogen stores were reduced but not depleted. ATP concentration was reduced in vivo but recovered in vitro. Diaphragmatic oxygen consumption was reduced in vitro at rest and during stimulation. The results suggest that endotoxemic shock results in diaphragmatic fatigue in a time-dependent fashion, that impaired neural or neuromuscular transmission is present in vitro, and that impaired oxygen consumption in the shocked diaphragm is associated with reduced high-energy-phosphate stores.

Topics: Adenosine Triphosphate; Animals; Diaphragm; Electric Stimulation; Glycogen; In Vitro Techniques; Male; Muscle Contraction; Osmolar Concentration; Oxygen Consumption; Rats; Rats, Inbred Strains; Shock, Septic

Considering the ubiquitous nature of glucocorticoid actions and the fact that endotoxin inhibits glucocorticoid action in the liver, we proposed to examine whether endotoxin affected extrahepatic actions of glucocorticoids. Fasted C57BL/6J mice were injected intraperitoneally with endotoxin (LD50) at 0800 and were killed 6 h later. Control mice were injected with an equal volume of saline. 3H-dexamethasone binding, measured by a new cytosol exchange assay utilizing molybdate plus dithiothreitol, in liver, kidney, skeletal muscle, spleen, lung, and heart tissue was significantly lower in treated than in control mice. The equilibrium dissociation constants were not significantly different, but the number of available binding sites in each tissue was reduced by endotoxin treatment. Phosphoenolpyruvate carboxykinase activity was significantly reduced in liver but not in kidney. Endotoxin treatment lowered glycogen content in liver but not in skeletal muscle. The reduction observed in the "a" form of liver glycogen synthase due to endotoxin was not seen in skeletal muscle glycogen synthase "a." These data support the proposal that endotoxin or a mediator of its action inhibits systemic glucocorticoid action. The results also emphasize the central role of the liver in the metabolic disturbances of the endotoxin-treated mouse.

Topics: Animals; Binding Sites; Dexamethasone; Endotoxins; Glucocorticoids; Glycogen; Glycogen Synthase; Liver; Liver Glycogen; Male; Mice; Mice, Inbred C57BL; Muscles; Phosphoenolpyruvate Carboxykinase (GTP); Receptors, Glucocorticoid; Salmonella typhimurium; Shock, Septic; Tritium

Respiratory muscle O2 consumption, lactate production, and endogenous substrate utilization during endotoxic shock were assessed in two groups of anesthetized spontaneously breathing dogs. In the endotoxin group (Escherichia coli endotoxin 10 mg/kg iv) and the sham group (saline iv), we sampled diaphragm, external intercostal, and gastrocnemius muscle tissue for glycogen and lactate concentrations before and after 3 h of the experimental period. Only in the endotoxin group did blood pressure and cardiac output decline significantly. Arterial O2 content did not change significantly during shock, whereas mixed venous, phrenic venous, and femoral venous O2 contents dropped to 8.0 +/- 1.1, 5.8 +/- 0.8, and 3.6 +/- 0.6 ml/dl at 60 min of shock, respectively, with little change thereafter. At 30 min of shock, femoral venous lactate rose higher than arterial values, whereas at 90 min of shock, onward, phrenic venous lactate was significantly higher than arterial concentrations. All muscle tissues showed significant lactate production and glycogen depletion after shock. In a second set of experiments we measured respiratory muscle blood flow during shock with radioactive microspheres. At 60 min of shock, diaphragmatic and intercostal blood flow rose by six- and twofold, respectively, whereas gastrocnemius blood flow declined significantly. We conclude that during endotoxin shock 1) the increased demands of the respiratory muscles are met by increasing blood flow and O2 extraction; 2) anaerobic metabolism and respiratory muscle substrate depletion, or both, may contribute to the observed fatigue.

Topics: Animals; Diaphragm; Dogs; Energy Metabolism; Glycogen; Lactates; Lactic Acid; Muscle Contraction; Muscle, Smooth; Oxygen Consumption; Regional Blood Flow; Respiratory System; Shock, Septic

Administration of endotoxin, a lipopolysaccharide extracted from cell walls of gram negative bacteria, elicited alterations in various metabolic parameters and in the electrocardiogram of rats. Cardiac glycogen and serum glucose were decreased, while serum pyruvate and acid phosphatase levels were increased. There was initial tachycardia followed by significant bradycardia and elevation of the ST segment in the animals with shock. Erythrocyte count, haemoglobin and haematocrit were not changed after shock. Treatment with naloxone caused significant decreases in the metabolic and electrocardiographic changes induced by endotoxin.

Topics: Acid Phosphatase; Alanine Transaminase; Animals; Blood Cell Count; Blood Coagulation; Blood Glucose; Electrocardiography; Female; Glycogen; Hemoglobins; Male; Myocardium; Naloxone; Rats; Rats, Inbred Strains; Shock, Septic

Leukocyte glycogen in rats was investigated by electron microscopy during the development of endotoxin shock. Although all white blood cells were examined, only mature neutrophils exhibited an increase in cytoplasmic glycogen. Such neutrophils were observed in the vascular spaces of liver, spleen, lung, and bone marrow including the hematopoietic compartment. The increase in glycogen occurred as early as 30 minutes after endotoxin treatment and continued steadily for 16 hours. The increased glycogen content in neutrophils may be due to increased glycogen synthesis. The increase in glucose uptake by neutrophils may contribute to the causes of hypoglycemia in the late phase of endotoxic shock.

Topics: Animals; Cytoplasmic Granules; Glycogen; Hypoglycemia; Male; Microscopy, Electron; Neutrophils; Rats; Rats, Inbred Strains; Shock, Septic; Time Factors

Topics: Adenosine Triphosphate; Animals; Assisted Circulation; Body Temperature; Carbon Dioxide; Dogs; Female; Glycogen; Hemodynamics; Intestine, Small; Intra-Aortic Balloon Pumping; Kidney; Klebsiella Infections; Liver; Male; Myocardial Contraction; Myocardium; Oxygen; Phosphocreatine; Respiration; Shock, Septic

Initial ultrastructural changes were studied in dog myocardium in endotoxin shock. Lesions of fine structure of myocardial cells, intravascular coagulation, and increased permeability of the histo-haematic barrier were found.

Topics: Animals; Capillaries; Disseminated Intravascular Coagulation; Dogs; Endothelium; Glycogen; Histocytochemistry; Mitochondria, Heart; Myocardium; Sarcoplasmic Reticulum; Shock, Septic

Topics: Animals; Carbohydrate Metabolism; Carbon Dioxide; Dogs; Fatty Acids; Glucose; Glycogen; Muscles; Oxygen Consumption; Proteins; Shock, Septic; Urea

Topics: Animals; Blood Glucose; Dexamethasone; Escherichia coli; Fructosephosphates; Gluconeogenesis; Glucosephosphates; Glycogen; Lactates; Liver; Phosphoenolpyruvate; Rats; Shock, Septic

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

Topics: Adenosine Diphosphate; Adenosine Monophosphate; Adenosine Triphosphate; Analysis of Variance; Animals; Blood Glucose; Blood Pressure; Carbon Dioxide; Escherichia coli; Glycogen; Glycolysis; Hydrogen-Ion Concentration; Lactates; Liver; Muscles; Myocardium; Oxygen; Phosphofructokinase-1; Phosphoglucomutase; Rabbits; Shock, Septic

Topics: Adaptation, Physiological; Animals; Choline; Depression, Chemical; Diethylstilbestrol; Endotoxins; Glycogen; Immunization; Iron; Mononuclear Phagocyte System; Oxides; Phagocytosis; Rats; Serum Albumin; Shock, Septic; Shock, Traumatic; Spleen; Stimulation, Chemical; Thorium Dioxide; Time Factors; Tissue Extracts; Wounds and Injuries; Zymosan

Topics: Adrenalectomy; Animals; Arteries; Blood Pressure; Carbohydrate Metabolism; Drug Tolerance; Endotoxins; Glucocorticoids; Glycogen; Heart Rate; Heart Ventricles; Hemodynamics; Injections, Intravenous; Lactates; Pressure; Pulse; Rats; Shock, Septic; Time Factors; Vagotomy