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Biomedical subjects

J J Spitzer

Publications and source records attributed to J J Spitzer.

At least 163 records · Page 9Linked to original sources
PubMed1980

Free fatty acid utilization by skeletal muscle after endotoxin administration.

The effect of endotoxin administration on free fatty acid (FFA) utilization by skeletal muscle was investigated. Albumin bound [1-14C]palmitate was continuously infused into anesthetized dogs. Blood samples from the carotid artery and profunda femoris veins were obtained and blood flow through the thigh muscles was determined. After endotoxin, skeletal muscle blood flow decreased by 29%, reflecting the average decrease in cardiac output. Arterial FFA concentration in endotoxin-treated animals was significantly reduced relative to saline-treated animals. Whole-animal FFA turnover decreased up to 37% after endotoxin. FFA uptake was linearly correlated with arterial FFA concentration both preceding and following endotoxin and the slopes of the regression lines were identical. FFA uptake by skeletal muscle was significantly reduced during the early postendotoxin time period. Skeletal muscle FFA oxidation after endotoxin also tended to decrease. It is concluded that the changes in skeletal muscle FFA metabolism are most likely due to decreased arterial FFA levels after endotoxin rather than a direct effect of endotoxin on skeletal muscle.

Animals↗
PubMed1980

Contribution of viable and nonviable heart myocytes to substrate oxidation.

An approach is described that allows metabolic data obtained from a mixture of vital dye-excluding (T-) and nonexcluding (T+) myocytes to be extrapolated to a homogeneous cell population. Myocytes from adult dog hearts were dispersed by enzymatic treatment and separated into two fractions: one containing predominantly T-, and the other containing predominately T+ cells. Measuring the oxidation rate and viability of each fraction allows the determination of the rate of oxidation of a homogeneous cell population when palmitate, glucose, or lactate is the oxidizable substrate. The calculated rate of oxidation of these substrates by 100% T- cells was: 0.15, 0.46, and 2.99 nmol . mg protein-1 . min-1, respectively. Oxidation of palmitate and lactate by T+ cells was one-fifth of the T-cell rate. Glucose oxidation of T+ cells was not significantly different from zero. Use of this procedure will permit study of myocardial metabolism when experimental procedures may cause altered cell viability.

Animals↗
PubMed1980

Effects of E coli endotoxin on pancreatic hormones and blood flow.

Studies were performed on anesthetized dogs to determine the relationship between endotoxin-induced alterations in pancreatic blood flow (PBF) and hormones that originate partially or completely from the pancreas. PBF was estimated in six dogs by radioactive microspheres (praeendoxin, 25 and 240 minutes postendotoxin). Insulin, glucagon, pancreatic polypeptide (PP), and somatostatin-like immunoreactivity (SLI) were assayed in arterial and portal venous blood. Cardiac output and mean arterial blood pressure (MABP) decreased 25 minutes after endotoxin administration (50% and 40%, respectively) and returned toward normal levels by four hours. However, there was 74% decrease in PBF at 25 minutes and a further drop four hours after endotoxin. Hormonal responses were characterized by a short-lived increase in arterial insulin, corresponding to a transient increase in blood glucose. Insulin release increased shortly after endotoxin. Arterial glucagon and PP increased two to five hours after endotoxin. There was a suggestion that the increase in PP was of nonpancreatic origin. Little change in plasma SLI was noted following endotoxin. Thus, it appears that endotoxin altered the release of different pancreatic hormones with a variable time courses.

Animals↗
PubMed1980

Total and regional cerebral blood flow during perfusion from the lateral ventricle to the cisterna magna in the conscious dog: effect of hemorrhagic hypotension and retransfusion on cerebral blood flow.

This study was performed to determine if autoregulation of regional cerebral blood flow (rCBF) occurs in conscious dogs with ventriculocisternal perfusion (VCP) during moderate hypotension. Six dogs were perfused for 360 minutes using mock cerebrospinal fluid (CSF). A 120-minute control period was followed by 180 minutes of moderate hemorrhagic hypotension (mean arterial pressure (SAP) 60-80 mm Hg). The lost blood (approximately 40% of the calculated blood volume) was retransfused after 300 minutes of perfusion, and an additional 60 minutes of observation concluded the study. The rCBF was measured at 120, 240, and 360 minutes of perfusion using labeled microspheres of 15 mu diameter. Cardiac output (CO) was 2.8 +/- 0.41 liters/min at 120 minutes, decreased to 1.4 +/- 0.10 liters/min after hemorrhage, and rose after retransfusion to 2.2 +/- 0.13 liters/min. The percentage of cardiac output (%CO) received by the brain was 1.8 +/- 0.37% at 120 minutes, 3.8 +/- 0.44% at 240 minutes, and 2.2 +/- 0.22% after retransfusion (P < 0.05). There was no significant change in rCBF during hypotension. The regional cerebral blood flow was, however, significantly elevated in the thalamus, mesencephalon, pons, and medulla after retransfusion indicated a local alteration of set point in the plateau of the autoregulatory curve. Cerebral venous pH (measured in internal maxillary venous blood) decreased significantly during hemorrhage to 7.25, while cerebral arteriovenous difference of oxygen and A-VpH increased significantly during hemorrhage. Thus, autoregulation of total cerebral blood flow (CBF) during acute moderate hypotension remains intact during VCP at a rate of 0.2 ml/min using a perfusate of a constant pH and, hence, CSF-pH appears not to be of major significance for the autoregulation of CBF in moderate hypotension.

Animals↗
PubMed1979

Increased free fatty acid turnover in CSF during hypotension in dogs.

Cerebrospinal fluid turnover rates of FFA were investigated using ventriculocisternal perfusion techniques. Seven conscious dogs were perfused over a 6-h period from the lateral ventricle to the cisterna magna with mock cerebrospinal fluid (CSF) containing [14C]palmitate and 100 mumol/l of FFA. One hundred and twenty minutes of perfusion were allowed to establish equilibrium of the FFA concentration in the ventricular space. Moderate hemorrhage hypotension was then induced (MABP greater than 60 mmHg) for 3 h, followed by rapid retransfusion and a final hour of perfusion. Cerebral blood flow did not change significantly (45 +/- 6 before, 53 +/- 6 after hemorrhage, and 47 +/- 5 ml.min-1. 100 g-1 after retransfusion). Cerebral arteriovenous difference of O2, glucose, and pH increased significantly during hemorrhage. Hypotension was accompanied by an increased turnover of FFA from 60 to 120 nmol/min (P less than 0.01) in the CSF. FFA turnover was directly correlated with the fatty acid concentration of the CSF (r = 0.77). It is speculated that the increased fatty acid turnover during hypotension may indicate increased phospholipid turnover and/or increased oxidation by tissues lining the ventricular space.

Animals↗
PubMed1979

Lipid metabolism in endotoxic shock.

A brief overview of the alterations in the control of free fatty acid (FFA) and triglyceride (TG) turnover following the administration of Escherichia coli endotoxin is presented. Hormone-sensitive lipase activity was increased following either in vivo or in vitro administration of endotoxin. In conscious dogs, the rate of appearance of glycerol was also increased while that of FFA was not changed, indicating that in addition to increased lipolysis, increased reesterification in the adipose tissue may also be present. Myocardial utilization of FFA was decreased and that of lactate increased following endotoxin both in vivo and in vitro using isolated myocytes. Both myocardial and adipose tissue lipoprotein lipase activity were decreased following endotoxin, indicating a possible decrease in TG removal by these tissues. Additional studies are warranted to further elucidate the interrelation between the changes of lipid and carbohydrate metabolism and those of hemodynamics in shock.

Adipose Tissue↗
PubMed1978

Fatty acid and lactate metabolism by heart homogenates from alloxan-diabetic dogs.

Myocardial homogenates from control of alloxan-diabetic dogs were incubated in the presence of lactate or palmitate as the sole substrate. The rate of lactate oxidation of the homogenates from diabetic dogs was less than half of the oxidation rate of homogenates from control animals. The incorporation of labelled palmitate into triglyceride was greatly enhanced in the heart taken from diabetic animals. The tissue concentration of l-carnitine was twice and that of triglyceride was three times as high in the diabetic animals as in their control counterparts. Thus the myocardium of diabetic animals exhibited both altered substrate utilization and increased rate of triglyceride synthesis.

Adenosine Triphosphate↗
PubMed1978

Effect of moderate hemorrhagic hypotension on cerebral metabolism during ventriculocisternal perfusion in the conscious dog.

Early changes in cerebral metabolism during hemorrhagic hypotension in conscious dogs have been studied with a chronic ventriculocisternal perfusion system. The mean arterial blood pressure was held above the lower limit of the cerebral autoregulatory curve. There was a rise of free fatty acids (FFA) in cerebrospinal fluid at 30 minutes after the onset of hemorrhage. The cerebral arteriovenous difference of oxygen (AVDO2), AVD-glucose, and AVD-pH increased significantly after 60 minutes of hemorrhage, while AVD-TCO2 (tissue culture oxygen) rose only slightly. These changes may reflect some of the metabolic alterations that occur in moderate hypotension.

Animals↗
PubMed1978

Glucose and lactate kinetics in guinea pigs following Escherichia coli endotoxin administration.

Glucose and lactate turnovers were evaluated during the early stages (first three hours) of endotoxin-induced shock in unanesthetized male guinea pigs following the intravenous (IV) administration of 0.1 mg of Escherichia coli endotoxin. Rate of appearance (Ra), rate of disappearance (Rd), and metabolic clearance rate (MCR) of glucose and lactate were determined by the primed-constant infusion of [6-(3)H]-glucose and NA L(+)[U-14C]-lactate. Arterial glucose concentration was moderately elevated, and the Ra and Rd of glucose were increased significantly following endotoxin administration, while the slight increase in MCR was not statistically significant. Arterial lactate concentration was markedly increased and the Ra and Rd of lactate were significantly elevated. The percentage of [14C]-glucose derived from [14C]-lactate increased from 19% (control) to above 50% following endotoxin. From these data we found no evidence of impaired peripheral extraction of glucose. The increased glucose Ra and the higher percentage of [14C]-glucose being derived from [14C]-lactate suggest increased gluconeogenesis during the early stages following endotoxin administration.

Animals↗
PubMed1977

Glucose kinetics in dogs following a lethal dose of endotoxin.

The effects of a lethal dose of Escherichia coli endotoxin on the glucose kinetics and cardiovascular responses of conscious dogs were studied. The plasma glucose level fell steadily after endotoxin administration to severely hypoglycemic levels preterminally. The fall in plasma glucose appeared to be due primarily to an increased tissue uptake in the early phase, whereas decreased hepatic glucose output also contributed in the later, preterminal phases.

Animals↗
PubMed1977

Glucose and lactate kinetics after endotoxin administration in dogs.

We studied the effects of E. coli endotoxin on the glucose and lactate kinetics in dogs by means of the primed constant infusion of [6(-3)H] glucose and Na-L-(+)-[U-14C] lactate. The infusion of endotoxin induced a transient hyperglycemic level, followed by a steady fall in plasma glucose to hypoglycemic levels. The rate of appearance (Ra) and the rate of disappearance (Rd) of glucose were both significantly elevated (P less than .05) for 150 min after endotoxin, after which neither differed from the preinfusion value. The metabolic clearance rate of glucose was significantly elevated at all times 30 min postendotoxin. By 30 min postendotoxin, Ra and Rd of lactate, plasma lactate concentration, and the percent of glucose turnover originating from lactate were significantly elevated and remained so for the duration of the experiment. We concluded that after endotoxin hypoglycemia developed because of an enhanced peripheral uptake of glucose and a failure of the liver to maintain an increased Ra of glucose. We also concluded that lactate became an important precursor for gluconeogenesis and an important metabolic substrate.

Animals↗
PubMed1977

Glucose and lactate kinetics in burn shock.

We studied the glucose and lactate kinetics during burn shock by means of the primed constant infusion of [6-3H]glucose and Na-L-(+)-[U-14C]lactate. We found an early postburn hyperglycemia that was due to an increased rate of appearance (Ra) of glucose. Later, the ability of the tissues to extract glucose became impaired, and the plasma glucose concentration increased even more in spite of the return of Ra of glucose to the control level. The Ra of lactate rose rapidly postburn, whereas the rate of disappearance (Rd) of lactate stayed at the control level for 30 min. Consequently, plasma lactate rose approximately 350%. After 30 min, Rd of lactate increased to the same level as Ra; and Ra, Rd, plasma lactate concentration, and the percent of glucose derived from lactate remained elevated for the duration of the experiment. These results indicate an important role of lactate in burn shock metabolism and substrate kinetics.

Animals↗
PubMed1977

In vitro effects of E. coli endotoxin on fatty acid and lactate oxidation in canine myocardium.

We studied the in vitro effect of E. coli endotoxin on the oxidation of palmitate, palmitoyl CoA, and lactate by canine heart homogenate. Heart homogenates were incubated in calcium-free Krebs-Ringer-phosphate buffer in the presence of a 14C-labeled substrate. Oxidation of the individual substrate was calculated from the rate of 14CO2 production. The rate of oxidation of palmitate, palmitoyl CoA, and lactate was proportionally inhibited by increasing amounts (80-800 microgram) of endotoxin. The decrease in substrate oxidation could be mimicked by adding calcium chloride to the tissue preparation, and could be effectively prevented by the chelating agent, EDTA. Ionic calcium was released from tissue stores during incubation of the tissue preparation with endotoxin. These findings demonstrate that E. coli endotoxin inhibits substrate oxidation by heart homogenates when incubated under in vitro conditions. The data also suggest that the inhibition may be mediated by ionic calcium released from the tissue in response to the action of endotoxin.

Animals↗