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J J Spitzer

Publications and source records attributed to J J Spitzer.

At least 145 records · Page 8Linked to original sources
PubMed1984

Depressed function of isolated hearts from hyperdynamic septic rats.

The aim of this study was to determine if hearts removed from rats in sustained hypermetabolic sepsis possessed normal physiological reserves as defined by Frank-Starling curves. The resting cardiac output of these hearts is elevated in vivo and this is mediated by an increased heart rate. In this study mechanical function was assessed under in vitro conditions in which preload could be varied and controlled. Isolated perfused working hearts from septic animals showed depressed cardiac performance, both in terms of peak systolic pressure development and cardiac output, over a range of left atrial filling pressures. In spite of this depressed function, most hearts from septic animals were able to recover cardiac output and pressure development following an acute ischemic episode. Thus, a loss of myocardial reserve is demonstrable in hearts isolated from septic rats, even though mean arterial blood pressure, cardiac output, and coronary blood flow are well maintained in vivo. This dysfunction is primarily evidenced by an inability to respond appropriately to increased preloads.

Animals↗
PubMed1983

Sustained hypermetabolic sepsis in rats: characterization of the model.

This paper describes the development of a sustained sepsis model, using chronically catheterized conscious unrestrained rats, which simulates the progression of septicemia in man, including a sustained hypermetabolic phase. Following chronic arterial catheterization, sepsis was induced in rats by intraperitoneal administration of 0.5 ml of a pooled fecal inoculum. The pooled inoculum, which was used to ensure a uniform inoculation of microorganisms to all animals, produced a septicemia which was progressively lethal. The resultant peritonitis was characterized as polymicrobial, with gram-negative bacteria being continuously present in both peritoneal fluid and blood. Septic animals were normotensive but tachycardic, compared to time-matched controls, throughout the observation period. In contrast to the stable colonic temperature of control animals, septic rats showed a significant febrile response on the first 3 days following inoculation. The hypermetabolic response in septic rats was also manifested by a 25, 38, and 28% increase in oxygen consumption on Days 1, 2, and 3 postinoculation. Animals responded to sepsis with a fall in blood glucose (on Day 2) which remained 15--20% below control levels. Mild hyperlactacidemia (2 mM) and reduced alanine concentrations (14--33%) were also seen in the septic group on Days 2 through 5. Despite the increased lactate levels, septic animals were mildly alkalotic (pH 7.51) which probably reflected the increased (32%) respiratory rate. Light microscopic findings in the septic animals revealed a spectrum of morphologic lesions including an extensive fibrinopurulent exudate, bacterial colonies, and abscesses, which involved most of the abdominal viscera. This investigation characterizes an experimental model of sustained sepsis in rats which exhibits hemodynamics, metabolic and pathologic alterations similar to those seen in human peritonitis.

Animals↗
PubMed1983

Exogenous substrate utilization by isolated myocytes from chronically diabetic rats.

The effect of chronic streptozotocin-induced diabetes on the utilization of exogenous substrates by freshly isolated, Ca2+-tolerant nonbeating myocytes was investigated. The rates of glucose (5 or 25 mM) and lactate (1 mM) oxidation were significantly reduced in myocytes of diabetic rats, whereas palmitate (0.4 or 1 mM) oxidation was similar to the controls. Glucose oxidation in diabetic (but not in control) and palmitate oxidation in control (but not in diabetic) myocytes were increased by raising the respective substrate concentrations in the medium to levels found in vivo in diabetic rats. Inhibition of glucose and lactate oxidation in the presence of competing substrates were generally similar between control and diabetic myocytes. However, the inhibitory effect of glucose on lactate oxidation was greater in control cells. The rate of palmitate oxidation was diminished by glucose in the controls, but this was not observed in the diabetic myocytes. Oxygen consumption by the myocytes of diabetic rats was below that of control cells when lactate or palmitate was present in the medium. ATP and phosphocreatine contents were similar in the myocytes of diabetic and control rats. All the observed changes in myocytes prepared from diabetic rats were reversed by in vivo insulin treatment.

Adenosine Triphosphate↗
PubMed1983

Effects of hypoxia and reoxygenation on adult rat heart cell metabolism.

Isolated adult rat heart cells were used to study the effects of oxygen deprivation followed by reoxygenation upon myocardial metabolism. Calcium-tolerant nonbeating myocytes were incubated for 5, 30, or 60 min under 100% oxygen or 100% nitrogen and then rinsed with oxygenated buffer. Substrate oxidation was studied by incubating the cells with 14C-labeled glucose, pyruvate, or octanoate and determining the rates of 14CO2 production from the individual substrates. After 5 min of hypoxia, metabolism of glucose, as assessed by glucose oxidation and lactate production, was significantly depressed. Pyruvate and octanoate oxidation were unaltered. Oxygen consumption was also unchanged by short-term hypoxia and reoxygenation. With reoxygenation after 30 min of oxygen deprivation, more exaggerated changes in glucose metabolism were noted as well as a depression in pyruvate oxidation and unaltered octanoate oxidation. Oxidation of octanoate was slightly depressed after 60 min of hypoxia. Cell viability assessed after reoxygenation was not significantly altered until 60 min of oxygen deprivation. The results indicate that cytosolic changes occur after short periods of hypoxia followed by reoxygenation, whereas mitochondrial function is more resistant to damage inflicted by hypoxia and reoxygenation.

Animals↗
PubMed1983

Metabolic clearance rate of ketone bodies in dogs following Escherichia coli endotoxin administration.

The metabolic clearance rates of ketone bodies were determined in anesthetized dogs following the intravenous administration of either Escherichia coli endotoxin or saline, in order to examine the influence of endotoxin on the efficiency of peripheral ketone body removal. A nonisotopic method was employed for these studies consisting of a stepwise infusion of beta-hydroxybutyrate at three different rates. At each infusion rate, a steady-state arterial concentration was reached, at which time the rate of appearance of ketone bodies equaled their removal rates. Rates of infusion were plotted against the steady-state arterial concentrations, and the reciprocal of the slope of this linear relationship represented the metabolic clearance rate. Administration of endotoxin did not alter the metabolic clearance rate of ketone bodies. The uptake of ketone bodies by the thigh muscles was also unaffected by endotoxin administration. It is concluded, that E. coli endotoxin does not influence the efficiency of peripheral ketone body removal.

3-Hydroxybutyric Acid↗
PubMed1982

Alterations in carbohydrate and lipid metabolism following administration of endotoxin.

Endotoxin-induced alterations in blood flow, carbohydrate and lipid metabolism in various organs of the body are outlined. Peripheral utilization of carbohydrates and lipids does not appear to be adversely affected by the administration of mild to moderate doses of endotoxin (in fact, glucose turnover is even elevated). On the other hand, the supply of free fatty acids from adipose tissue is diminished, at least in part, due to severe hemodynamic changes that occur in this tissue following endotoxin. Hepatic gluconeogenesis is elevated, but does not match the increased demand for glucose by the periphery. The experimental conditions discussed in this brief review elicit changes that are reversible. However, during more severe endotoxemia, the metabolic alterations lead to irreversibility.

Adipose Tissue↗
PubMed1982

Metabolic and hormonal changes following endotoxin administration to diabetic rats.

The aim of these investigations was to study the time course and cause of the altered metabolic response of diabetic rats to endotoxin administration. Escherichia coli endotoxin was administered to streptozotocin-diabetic and control normoglycemic rats. At 1, 2, 5, 8, and 24 h following endotoxin, animals were decapitated. Plasma samples were analyzed for glucose, lactate, insulin, glucagon, and corticosteroids. In addition, tissue glycogen content of liver and skeletal muscle was determined. Endotoxin caused an elevation of plasma glucose in both diabetic and normoglycemic rats by 1 h postinjection. The elevation was prolonged in diabetic rats for 8 h but lasted only 2 h in nondiabetic rats. Both endotoxin-treated groups demonstrated hyperlactacidemia following endotoxin. Endotoxin led to liver glycogen depletion in both diabetic and normoglycemic rats, whereas muscle glycogen content was only slightly affected. Plasma glucagon and corticosteroids rose immediately and remained elevated in both endotoxin-treated groups. A significant insulin response to rising plasma glucose was observed in nondiabetic but not in diabetic rats following endotoxin. These results suggest that the exaggerated and prolonged hyperglycemia observed in diabetic endotoxin-treated rats is due to hypersecretion of glucose-mobilizing hormones and elevated gluconeogenesis, unmatched by an adequate secretion of insulin to promote glucose uptake and utilization.

Adrenal Cortex Hormones↗
PubMed1982

Glucose turnover five hours following endotoxin administration to normal and diabetic rats.

Glucose turnovers were measured in fasted anesthetized diabetic and normal rats prior to and 5 hours following Escherichia coli endotoxin (ET) administration. Plasma glucose, lactate, blood pH, and hematocrit were also measured. Blood pressure, heart rate, and urine flow were monitored throughout. ET treatment led to an equivalent fall in blood pressure in both diabetic and normal rats, accompanied by a rising heart rate. ET treatment resulted in a significant elevation of plasma glucose in diabetic, but not in normal rats. Plasma lactates rose in both ET-treated groups endotoxin increased glucose turnover both in diabetic and normal rats. ET did not alter glycosuria of diabetic rats, and urine flow was not affected. A significant increased urine flow was measured in normal ET rats. The results reported here indicate that hepatic glucose output was increased by ET treatment in both normal and diabetic rats, and that this elevation was maintained for at least 5 hours. Metabolic clearance rate of glucose was not altered in the diabetic rats following ET, although it was markedly elevated in the normal animals. This, the insulin-like effect of ET as indicated by changes in metabolic clearance rate was absent in the diabetic rats.

Animals↗
PubMed1981

Exogenous substrate utilization in Ca2+-tolerant myocytes from adult rat hearts.

A preparation of isolated noncontracting adult rat heart myocytes can be obtained in which viability is high, yield is adequate, and the cells are not sensitive to the deleterious effects of Ca2+ at physiological levels. Myocytes are enzymatically dispersed and maintained in a medium containing amino acids and 1% bovine serum albumin at 37 degrees C. The initial viability of 77% fell to 70% after a 60-min incubation in the presence of 1.5 mM Ca2+. The initial cellular ATP content of the myocytes was 27 nmol/mg protein. Cellular ATP content fell to 21 and 17 nmol/mg protein when cells were incubated for 60 min with and without 1.5 mM Ca2+, respectively. The oxidation of glucose and lactate was increased by 50 and 30%, respectively, by the addition of Ca2+. A decrease in the oxidation rate of these two substrates was noted when the myocytes were incubated with medium containing ethyleneglycol-bis(beta-aminoethylether)-N,N'-tetraacetic acid. No changes in the rate of palmitate oxidation were observed. The significant increase in glucose and lactate oxidation due to ca2+ provides further evidence that ca2+ influences myocardial substrate utilization independent of its effects on mechanical performance of the myocardium.

Adenosine Triphosphate↗
PubMed1981

Influence of Escherichia coli endotoxin on palmitate, glucose, and lactate utilization by isolated dog heart myocytes.

The in vitro effects of E. coli 0127:B8 endotoxin on the oxidation of palmitate, glucose, and lactate by isolated, beating, adult dog heart myocytes were studied. The result were correlated with the in vitro effect of endotoxin on the transport of palmitate and glucose by using their respective analog, hexadecanol and 3-O-methyl-D-glucose. Endotoxin decreased palmitate but increased glucose and lactate oxidation in a dose-dependent manner. The changes in palmitate and lactate oxidation induced by endotoxin could not be corrected by addition of L-carnitine to the reaction mixture. The transport of hexadecanol or of 3-O-methyl-D-glucose was not affected by endotoxin. These results suggest that the endotoxin-induced alteration in palmitate and glucose oxidation by the heart is not the result of an impairment in metabolite transport, but rather a defect in the subsequent intracellular oxidative processes.

Animals↗
PubMed1981

Increased tissue lipoprotein lipase activity in guinea pigs following burn trauma.

Accelerated clearance of circulating triglycerides has been observed in thermally injured patients, which suggests that lipoprotein lipase (LPL) activity may be increased. The present study was initiated to ascertain if heart, skeletal muscle, or adipose tissue LPL activities are affected by burn trauma in guinea pigs. Anesthetized guinea pigs were immersed into room temperature water (nonburned) or boiling water (burned) to the iliac crest for three seconds and sacrificed seven or 24 hours later. Myocardial and adipose tissue LPL activities were 60% and 125% greater, respectively, in burned guinea pigs 24 hours after injury than in nonburned animals. LPL activity in skeletal muscle from the burned region, red vastus, was significantly increased seven hours after injury, but the change after 24 hours was not significant. Muscle LPL activities examined in the nonburned region, diaphragm and red triceps, were increased 24 hours after thermal injury. Increased tissue LPL activities after thermal injury may enhance the clearance of circulating triglycerides.

Adipose Tissue↗
PubMed1981

Increased muscle oxygen consumption during electrical stimulation following endotoxin administration.

In this study, skeletal muscle oxygen demand was increased by electrical stimulation to determine if restricted oxygen supply to skeletal muscle in endotoxin-treated dogs was limiting oxygen consumption. Skeletal muscle blood flow was measured directly and arterio-venous differences of oxygen were determined in hindlimb muscles by obtaining blood samples simultaneously from the carotid artery and profunda femoris veins. Hindlimb muscle stimulation did not influence the systemic hemodynamic parameters monitored in either saline or endotoxin treated animals, although endotoxin treated animals demonstrated the well-characterized hemodynamic changes. During stimulation, skeletal muscle oxygen consumption was elevated due to increased oxygen extraction and blood flow in both treatment groups. No significant difference in oxygen consumption by nonstimulated muscle was observed between treatment groups. However, muscle oxygen extraction following endotoxin was greater than either pre-treatment or saline extraction values. This study demonstrates that following endotoxin administration, oxygen extraction by skeletal muscle is not maximal, and the muscle can further increase oxygen extraction with greater oxygen demand. Thus, skeletal muscle oxygen supply is not limiting the oxygen consumption following endotoxin treatment.

Animals↗
PubMed1980

The effect of endotoxin on plasma alpha-aminoisobutyric acid.

The i.v. injection of bacterial endotoxin into dogs was found to cause a rapid increase in plasma levels of infused alpha-aminoisobutyric acid. The findings suggest that nonmetabolic factors (tissue uptake, fluid shifts) influence amino acid distribution during endotoxemia.

Aminoisobutyric Acids↗
PubMed1980

Glucose metabolism following endotoxin administration in diabetic rats.

The altered glucose metabolism characteristic of endotoxin-induced shock was studied in diabetic and non-diabetic rats. Endotoxin administration led to an exaggerated hyperglycemia in the diabetic rats. The exaggerated hyperglycemia appeared to be a consequence of an increased hepatic output of glucose, presumably via gluconeogenesis, as evidenced by an exaggerated glucose turnover following endotoxin. Diabetic and non-diabetic rats responded to endotoxin similarly with respect to blood pressure, heart rate, hematocrit, blood pH and plasma lactate. Endotoxin administration did not affect urine flow rate or urinary glucose excretion in either diabetic or non-diabetic rats.

Animals↗
PubMed1980

Increased muscle glucose uptake and lactate release after endotoxin administration.

Changes in glucose uptake and lactate and alanine release by skeletal muscle were studied in anesthetized dogs before and over a 4-h period after endotoxin administration and in time-matched controls. Blood flow was measured directly, and arteriovenous differences of glucose, lactate, alanine, and O2 were determined in hindlimb muscles by obtaining blood samples simultaneously from the carotid artery and profunda femoris veins. Skeletal muscle blood flow decreased by 29% after endotoxin, reflecting a similar average decrease in cardiac output. Mean arterial glucose decreased 31% and arterial lactate and alanine increased 201 and 123%, respectively, after endotoxin administration. Skeletal muscle glucose uptake increased 57% after endotoxin despite the progressively developing hypoglycemia. Postendotoxin lactate and alanine release were also elevated by 217 and 82%, respectively. Average O2 consumption by skeletal muscle did not change. The metabolic pattern observed after endotoxin administration suggests that the increased lactate and alanine release are likely to be related to the elevated glucose uptake and that skeletal muscle greatly influences the metabolic pattern observed during shock.

Alanine↗