Biomedical subjects

C H Lang

Publications and source records attributed to C H Lang.

At least 181 records · Page 10Linked to original sources

PubMed1986

Plasma glucose concentration determines direct versus indirect liver glycogen synthesis.

In the present study hepatic glycogenesis by the direct versus indirect pathway was determined as a function of the glucose infusion rate. Glycogen synthesis was examined in catheterized conscious rats that had been fasted 48 h before receiving a 3-h infusion (iv) of glucose. Glucose, containing tracer quantities of [U-14C]- and [6-3H]glucose, was infused at rates ranging from 0 to 230 mumol X min-1 X kg-1. Plasma concentrations of glucose, lactate, and insulin were positively correlated with the glucose infusion rate. Despite large changes in plasma glucose, lactate, and insulin concentrations, the rate of hepatic glycogen deposition (0.46 +/- 0.03 mumol X min-1 X g-1) did not vary significantly between glucose infusion rates of 20 and 230 mumol X min-1 X kg-1. However, the percent contribution of the direct pathway to glycogen repletion gradually increased from 13 +/- 2 to 74 +/- 4% in the lowest to the highest glucose infusion rates, with prevailing plasma glucose concentrations from 9.4 +/- 0.5 to 21.5 +/- 2.1 mM. Endogenous glucose production was depressed (by up to 40%), but not abolished by the glucose infusions. Only a small fraction (7-14%) of the infused glucose load was incorporated into liver glycogen via the direct pathway irrespective of the glucose infusion rate. Our data indicate that the relative contribution of the direct and indirect pathways of hepatic glycogen synthesis are dependent on the glucose load or plasma glucose concentration and emphasize the predominance of the indirect pathway of glycogenesis at plasma glucose concentrations normally observed after feeding.

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PubMed1986

Effects of glucose-insulin-potassium on intestinal hemodynamics and substrate utilization during endotoxemia.

This study examined the effects of endotoxin on small intestinal hemodynamics and metabolism with and without an infusion of glucose-insulin-potassium (GIK). Glucose uptake and lactate release were determined by arteriovenous differences across a segment of canine ileum, which was vascularly isolated in vivo, and by the direct measurement of intestinal blood flow. Free fatty acid (FFA) utilization by intestinal tissue was assessed by the constant infusion of albumin-bound [14C]palmitate and [3H]oleate. Endotoxemic dogs showed a sustained reduction of mean arterial blood pressure (MABP) and intestinal blood flow. In contrast, endotoxemic dogs infused with GIK demonstrated a decreased intestinal vascular resistance and an increased blood flow (two-fold), whereas MABP was transiently improved. Intestinal glucose uptake was not different from control values in endotoxemic animals; however, a sixfold increase was seen in shocked dogs treated with GIK. The endotoxin-induced increase in the plasma lactate concentration and intestinal lactate release was similar between dogs infused with saline or GIK. After endotoxin, the arterial FFA concentration remained unchanged and whole-body FFA turnover was decreased. FFA uptake by the gut was reduced, but FFA oxidation was not altered. Similar changes in FFA metabolism were seen in endotoxemic animals infused with GIK. The metabolic pattern after endotoxin suggests an elevated rate of aerobic glycolysis by the gut that increases the availability of lactate to the liver. Compared with saline-infused endotoxemic animals, GIK produced an elevation in glucose uptake without a further increase in lactate output, suggesting an increased storage of glucose by this tissue.

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PubMed1986

In vitro myocardial performance after lethal and nonlethal doses of endotoxin.

The present study was initiated to determine whether the myocardial effects of an in vivo injection of endotoxin into rats were correlated with the dose and thus the lethality of the endotoxin administered. All animals in this study were used 4 h after a bolus injection of 1,000, 100, 10, or 1 microgram/100 g body wt of Escherichia coli endotoxin. At this time, mean arterial blood pressure had returned to control levels but cardiac output was still depressed at the three higher doses as previously reported [Am. J. Physiol. 248 (Regulatory Integrative Comp. Physiol. 17): R471-R478, 1985]. Intrinsic function of the myocardium was assessed using the isolated perfused working heart preparation. Cardiac output and pressure development were measured at varying preloads and at two levels of aortic outflow resistance. In vitro approaches were chosen for this study to eliminate peripheral vascular changes and humoral or neural alterations that might influence myocardial performance in vivo. Results indicate that coronary vascular resistance was increased in all hearts from endotoxin-treated animals compared with controls. In addition, myocardial performance was impaired at several doses of endotoxin, and the degree of dysfunction was dependent on the dose of endotoxin administered. Dysfunction, i.e., a depression in cardiac output times peak systolic pressure, was evident at the two higher doses in which there was 50 and 10% lethality by 24 h and also in the lower dose of 10 micrograms/100 g, which was nonlethal. Cardiac output appeared to be very sensitive to the consequences of endotoxin administration. Defects in myocardial performance could be revealed by increasing preload or afterload stress on the hearts.(ABSTRACT TRUNCATED AT 250 WORDS)

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PubMed1986

Glycogen synthase and phosphorylase activities during glycogen repletion in endotoxemic rats.

The activities of glycogen synthase and glycogen phosphorylase were quantitated in liver and skeletal muscle removed following glucose infusion in hemodynamically stable endotoxin-treated rats. Four hours after the IV injection of endotoxin or saline, rats were infused with 235 mumole/min/kg of glucose or saline for up to 4 additional hr. Saline-infused endotoxemic rats had lower basal glycogen content in muscle and liver, which was associated with an increased phosphorylase a activity in both tissues compared to controls. During the glucose infusion, the rate of glycogen repletion in muscle was similar in the two groups. Skeletal muscle phosphorylase a and glycogen synthase I & D activities were elevated above control values in endotoxemia, while glycogen synthase I activity remain unchanged. These changes in the activity of muscle phosphorylase and synthase are consistent with an increased flux of carbon into and out of glycogen and a normal rate of net glycogen synthesis during glucose infusion in endotoxin-treated rats. In contrast to muscle, hepatic glycogen synthesis by endotoxemic animals was reduced compared to glucose-infused controls. Hepatic glycogen repletion in control animals appeared to be mediated primarily by a glucose-induced suppression of phosphorylase a activity rather than an increased glycogen synthase activity. Glucose infusion failed to decrease phosphorylase a activity in endotoxin-treated rats, which may be causally related to the impaired ability of these animals to replete liver glycogen.

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PubMed1986

Regional blood flow during continuous low-dose endotoxin infusion.

Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Cardiac output and regional blood flow were determined by the radiolabeled microsphere method after 6 and 30 hr of ET or saline infusion. Cardiac output (CO) of ET rats was not different from time-matched controls, whereas arterial pressure was 13% lower after 30 hr of infusion. After both 6 and 30 hr of ET, pancreatic blood flow and percentage of cardiac output were lower than in controls. Estimated portal venous flow was decreased at each time point, and an increased hepatic arterial flow (significant after 30 hr) resulted in an unchanged total hepatic blood flow. Blood flow to most other tissues, including epididymal fat, muscle, kidneys, adrenals, and gastrointestinal tract, was similar between treatments. Maintenance of blood flow to metabolically important tissues indicates that the previously reported alterations in in vitro cellular metabolism are not due to tissue hypoperfusion. Earlier observations of in vitro myocardial dysfunction, coexistent with the significant impairment in pancreatic flow, raise the possibility that release of a myocardial depressant factor occurs not only in profound shock but also under less severe conditions of sepsis and endotoxemia.

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PubMed1986

Endotoxin tolerance diminishes endotoxin-induced alterations in carbohydrate kinetics.

This study was designed to determine if attenuated mortality to a challenge dose of endotoxin was accompanied by or separated from alterations in glucose metabolism in endotoxin-tolerant rats. The in vivo effects of endotoxin were studied in catheterized endotoxin-tolerant rats and nontolerant control animals. Tolerance was induced by iv injections of 100 micrograms endotoxin/100 g BW (tolerance dose) for either 2 or 4 consecutive days; control rats received daily saline injections. On the day after the final tolerance dose, glucose kinetics were assessed by the constant infusion of [6-3H]-glucose prior to and after a challenge dose of endotoxin (1,000 micrograms/100 g) in tolerant and nontolerant rats. Following the challenge dose, 2-day tolerant animals exhibited an improved survival at 72 hr (LD 14 vs LD 92), a significantly smaller reduction in mean arterial blood pressure (20 vs 34%), and smaller increases in plasma glucose (9.4 +/- 0.6 vs 11.4 +/- 0.6 mM) and lactate (3.2 +/- 0.3 vs 8.5 +/- 1.4 mM) concentrations, compared to those in nontolerant control rats. However, increases in the rates of glucose appearance (Ra) and metabolic clearance (MCR) were not diminished. In 4-day tolerant rats, lethality to endotoxin was abolished, and no alterations in blood pressure or glucose kinetics were seen during the 4-hr period after endotoxin. However, the basal glucose Ra and MCR determined prior to endotoxin challenge were elevated in these rats compared to controls. Hyperglucagonemia was evident following the endotoxin challenge in control and 2-day tolerant rats, but not in 4-day tolerant animals. The hypothermia seen in nontolerant rats 4 hr after endotoxin was not present in either group of tolerant animals. The results show that after 2 days, tolerant animals have improved survival rates when challenged with endotoxin but still demonstrate acute changes in glucose kinetics. A complete protection against a normally lethal dose of endotoxin exists after 4 days. At this stage, rats showed no transient hemodynamic or metabolic alterations following endotoxin challenge.

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PubMed1986

Increased glucose metabolism by epitrochlearis muscle removed from endotoxin-treated rats.

In this study glucose metabolism was assessed in epitrochlearis muscle taken from control and endotoxin-treated rats. Endotoxin (1 mg/100 g) or saline was administered i.v. to rats and the epitrochlearis muscle was removed 3 hr later for in vitro incubation. Glycolysis, determined as 3H2O production from [2-3H]-glucose, was increased 45% in muscle taken from endotoxin-treated rats compared to control animals. Glycogen synthesis, assessed by the incorporation of [U-14C]-glucose into glycogen, was similarly elevated. Glycolysis and glycogen synthesis were stimulated by insulin in a dose-dependent manner. Muscles removed from endotoxin-treated rats were slightly more sensitive to insulin, but at the highest dose of insulin used, differences between muscles from control and endotoxemic rats remained similar to differences seen without insulin. Endotoxin-induced changes in glucose metabolism were not reversed by the presence of indomethacin, indicating that prostaglandin production is not responsible for these changes. Thus, endotoxemia results in changes in glucose metabolism in skeletal muscle that are retained in vitro in the absence or presence of insulin.

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PubMed1986

Substrate utilization and high energy phosphate levels of hearts from hyperdynamic septic rats.

Experiments were conducted to test the hypothesis that the previously demonstrated depression in ventricular function of rats with hyperdynamic sepsis was a result of depressed high energy phosphate levels or altered myocardial substrate utilization. Rats were inoculated with a pooled fecal homogenate, and 48 hr later their hearts were removed and studied using the Langendorff preparation. The coronaries were perfused with a hydrostatic pressure of 90 mmHg, and hearts were paced at 310-320 beats/min. Substrate oxidation was determined by supplying 14C-labeled glucose, lactate, or palmitate in physiologic concentrations, ie, 5.5, 1, and 0.6 mM, respectively. Hearts were frozen either in situ or after 40-50 min of perfusion for the determination of tissue metabolite levels. Myocardial content of high energy phosphates, total adenine nucleotides, and creatine were similar in septic animals and time-matched controls both in situ and after perfusion. Oxidation of exogenous substrates accounted for the total myocardial O2 consumption in both groups of perfused hearts. Palmitate oxidation was responsible for approximately 50% of the total O2 consumption of the heart, with glucose accounting for approximately 20% and lactate for the remainder. The percentage contribution of the three substrates to oxidative metabolism was similar in hearts from septic and time-matched controls; therefore, myocardial substrate preference was not altered by sustained sepsis. These studies also indicate that ischemia and the concomitant fall in high energy phosphates do not contribute to the myocardial dysfunction of hyperdynamic sepsis.

Adenine Nucleotides↗

PubMed1985

Glucose kinetics and body temperature after lethal and nonlethal doses of endotoxin.

Rats were injected with doses of endotoxin ranging from 1,000 [lethal dose approximately 50% (LD50)] to 0.01 microgram/100 g, and alterations in hemodynamics, glucose kinetics, and body temperature were studied over the subsequent 4 h. Doses of 10 micrograms/100 g or less were consistently nonlethal over 72 h. Decreases in arterial blood pressure and cardiac output were evident in rats receiving 1,000-10 micrograms/100 g endotoxin. Doses of endotoxin between 1,000 and 10 micrograms produced an early hyperlactacidemia evident by 1 h, whereas the lower doses (1 and 0.1 microgram) induced elevations that exhibited a delayed temporal response. The rates of glucose appearance (Ra) and disappearance (Rd) were increased early and transiently by the higher doses of endotoxin. Lower doses increased glucose Ra and Rd between 2 and 4 h after endotoxin. A febrile response was elicited by 10, 1, and 0.1 microgram/100 g endotoxin, while hypothermia was seen in animals receiving higher doses. Thus high doses of endotoxin induced metabolic and hemodynamic alterations that were temporally associated. Very low nonlethal doses of endotoxin (up to 4 orders of magnitude less than LD50) induced metabolic changes that appeared to be independent of hemodynamic disturbances but were temporally associated with the observed hyperthermia.

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PubMed1985

Myocardial dysfunction in a nonlethal, nonshock model of chronic endotoxemia.

Escherichia coli endotoxin (ET) was administered to adult rats by continuous IV infusion from a subcutaneously implanted osmotic pump (Alzet). Myocardial function was assessed after 6 and 30 hr of ET infusion and compared with control rats which received a saline infusion and were fasted to match the anorexia of ET rats. Cardiac output (CO) and coronary blood flow, measured by the radiolabeled microsphere method, and mean arterial blood pressure, heart rate, total peripheral resistance, and stroke volume, were determined in vivo. Treatment differences were limited to a 13% lower arterial pressure in ET rats after 30 hr of infusion. Myocardial function was evaluated in vitro in similarly treated rats with the isolated perfused working heart preparation; preload was altered by raising the left atrial filling pressure (LAFP) from 10 to 30 cm water. After both 6 and 30 hr of infusion, hearts from ET rats exhibited a significantly lower peak systolic pressure (PSP), CO, and coronary flow in response to increasing LAFP, and a greater oxygen consumption per unit of myocardial work (CO X PSP). Reduced in vitro work performance of hearts from endotoxemic rats was demonstrated early in the course of chronic endotoxemia and in the absence of in vivo evidence of cardiac dysfunction. Myocardial dysfunction, masked in vivo by compensatory mechanisms used to maintain adequate cardiovascular function, may be an important feature in the pathogenesis of both experimental endotoxemia and clinical gram-negative sepsis.

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PubMed1985

The effect of hyperdynamic sepsis on myocardial performance.

The reviewed studies support the contention that during the high flow or hyperdynamic phase of gram-negative septicemia, cardiac reserve is compromised because of intrinsic myocardial dysfunction. The latter is not referable to coronary hypoperfusion or peripheral pooling or decreased venous return. Although, under resting, nonstressed conditions, indices of myocardial function may appear normal or even elevated, a decreased reserve is evident when additional stress is imposed on the myocardium. Hearts removed from septic rats during the hyperdynamic stage and perfused in vitro (using the isolated perfused working heart preparation) showed a rightward and downward shift in work function curves, indicating a severe depression in cardiac function. Possible mechanisms for the observed dysfunction are discussed. No significant alterations in high energy phosphate production or substrate utilization were observed, indicating that altered myocardial metabolism is not likely to be a significant contributor to the dysfunction. Our results suggest that cardiac dysfunction is partially due to an elevation in the cytosolic calcium concentration which may slow the rate of ventricular relaxation. These studies emphasize that intrinsic cardiac function is depressed early during the course of the septic episode at a time that precedes the onset of circulatory shock.

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PubMed1985

Effect of cardiotropic agents on the myocardial dysfunction of hyperdynamic sepsis.

We have previously shown that in vitro myocardial performance is impaired in rats during the hyperdynamic, hypermetabolic phase of sepsis. Although the heart in the resting animal generated an elevated cardiac output, the isolated, perfused heart showed a depressed ventricular function curve. In the present studies, interventions to improve contractile function (increased perfusate calcium concentration or perfusion with ouabain) or to decrease calcium availability to the myofibrils (verapamil and tetracaine) were investigated using the isolated perfused working heart. These studies showed that increasing or decreasing calcium concentration in the perfusion medium had little effect on ventricular performance in the septic group, whereas ouabain enhanced performance by approximately 25%. Addition of verapamil at a dose that caused a minimal decrease in myocardial work (cardiac output X peak systolic pressure) in control hearts showed a 20-25% increase in work in the experimental hearts. Increased levels of verapamil caused a greater depression in myocardial performance in the control hearts than in the hearts from septic rats. Thus, it appears that a multifaceted defect may be present in these hearts with a derangement that can be slightly improved with either ouabain or verapamil. Since neither intervention could completely reverse the myocardial dysfunction in hyperdynamic sepsis, it appears that the defect may be due to other factors in addition to calcium availability for contraction.

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PubMed1985

Effects of toxic and nontoxic endotoxin derivatives on glucose kinetics.

Although the polysaccharide portion of bacterial endotoxins (ET) and other components of the bacterial cell wall are known to possess biological activity, the toxic effects produced by ET have been attributed mostly to the lipid-A component. The present study examined the influence of selected gram-negative cell wall components on in vivo carbohydrate homeostasis. Chronically catheterized conscious rats were injected with either ET, lipid A, the White polysaccharide supernatant (WPS-S; polysaccharide-rich and lipid-A-free) or the WPS-precipitate (WPS-P; rich in cell wall components and lipid-A-free) at sublethal doses of 100, 10, and 1 microgram/100 g. The acute hypotensive response to ET and lipid A were similar, while the WPS-P induced a smaller reduction in pressure. Endotoxin, lipid A, or the WPS-P (100 and 10 micrograms) all produced hyperglycemia. Hyperlactacidemia was evident in rats receiving ET, lipid A, and WPS-P; ET-treated animals exhibited the highest lactate concentrations. At the highest doses used, these three fractions increased the rate of glucose appearance. The polysaccharide-rich WPS-supernatant elicited no significant alterations in any of the variables studied. These results indicate that cell wall components of gram-negative bacteria, other than the lipid A of endotoxin, induce changes in carbohydrate metabolism that are similar to those produced by the toxic, lipid-A component of endotoxin.

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PubMed1984

Hypertriglyceridemia and its relation to tissue lipoprotein lipase activity in endotoxemic, Escherichia coli bacteremic, and polymicrobial septic rats.

Hypertriglyceridemia, commonly observed in septic patients, may result from a decreased ability of tissues to remove plasma triacylglycerol due to depressed lipoprotein lipase activity. While endotoxin administration results in substantial decreases in muscle lipoprotein lipase activity, enzyme activity is increased in animals subjected to other forms of stress and trauma. The present study was initiated to compare changes in plasma triacylglycerol concentrations and tissue lipoprotein lipase activities in rats challenged with endotoxin or live Escherichia coli (iv or ip) or rats subjected to polymicrobial peritoneal sepsis. Sixteen hours post-treatment plasma triacylglycerol levels were increased 200 to 300% in endotoxin- and E. coli-treated rats but did not differ from control animals subjected to peritoneal sepsis. At the same time, endotoxin administration resulted in significant decreases in heart (71-80%), soleus muscle (52-74%), and adipose tissue (21-32%) lipoprotein lipase activity regardless of the route injected. Intravenous E. coli also lead to a decrease in the three tissues examined while ip administration of E. coli reduced muscle and adipose tissue but not heart lipoprotein lipase activity. In contrast to endotoxemic and E. coli bacteremic rats, polymicrobial peritonitis resulted in significant increases in heart (46-89%) and skeletal muscle (18-39%) lipoprotein lipase activity. Thus, hypertriglyceridemia is not necessarily a consequence of sepsis but occurred in endotoxemic and bacteremic states when muscle and adipose tissue lipoprotein lipase activities were reduced. These findings support the postulate that sepsis-induced hypertriglyceridemia is likely to be associated with a decreased ability of lipoprotein lipase-containing tissues to clear circulating triacylglycerol.

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PubMed1984

Carbohydrate dynamics in the hypermetabolic septic rat.

Glucose turnover is increased during shock and in acute sepsis, but relatively little information is available concerning the regulation of carbohydrate metabolism during the hypermetabolic phase of sepsis. In these studies peritoneal sepsis was induced in rats, following chronic vascular catheterization, by intraperitoneal administration of a pooled fecal inoculum. The resultant peritonitis has been shown to produce a sustained hypermetabolic state during the first three days of infection. Glucose and lactate kinetics were studied using a constant infusion of radiolabeled tracers during the peak of the hypermetabolic phase (day 2). The septic animals exhibited a 42% increase in glucose turnover and a 63% increase in the metabolic clearance rate of glucose, as compared to time-matched control rats. Hepatic glycogenolysis could only contribute 1% to 2% to the increased rate of glucose appearance. A major portion of the elevated glucose turnover was accounted for by a 93% increase in glucose recycling, indicating an enhancement of gluconeogenesis from glucose-derived gluconeogenic precursors. The increased importance of lactate as a precursor for gluconeogenesis in sepsis was indicated by the elevated lactate turnover (34%) and the increased percentage of 14C-glucose derived from 14C-lactate. The insulin to glucagon ratio was decreased in the septic animals as a result of a reduction in the plasma insulin concentration (56%) and an increased glucagon concentration (67%). We conclude that during the hypermetabolic phase of sepsis, the increased peripheral glucose uptake generated more gluconeogenic precursors but did not appear to have a major direct contribution to the increased aerobic metabolism.

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PubMed1984

Cardiac output and redistribution of organ blood flow in hypermetabolic sepsis.

Cardiac output (CO) and the distribution of blood flow were studied in chronically catheterized conscious rats during sustained (4 days) sepsis. Septicemia was induced by intraperitoneal administration of a pooled fecal inoculum, and tissue blood flow and CO were determined daily with 15-micron radioactive microspheres. Mean arterial blood pressure (MABP, 113 +/- 2 mmHg), CO (244.5 +/- 11.4 ml X min-1 X kg-1), and total peripheral resistance (TPR, 1.36 +/- 0.07 mmHg X ml-1 X min) were stable in control rats over the 4 days postinoculation. Septic animals showed a consistent tachycardia with MABP significantly reduced only on days 3 and 4 (86 +/- 4 mmHg). A hyperdynamic response to sepsis was indicated by an elevated CO (27%) and similarly reduced TPR on day 2. The calculated stroke volume averaged 0.22 +/- 0.01 ml/beat and did not vary over time or between the two groups. There was a 40-70% increase in blood flow to the heart, spleen, adrenal glands, and small intestine, and a greater than sixfold increase in hepatic arterial blood flow. The sustained elevation of coronary blood flow, observed in septic animals, was independent of myocardial work and is consistent with impaired myocardial function. Pancreas, stomach, and skeletal muscle blood flow was consistently compromised (24, 39, and 52%, respectively) during sepsis. Blood flow in other organs remained unchanged over time. Sepsis-induced changes in the fractional distribution of blood flow to various organs were similar to those described for absolute flow. (ABSTRACT TRUNCATED AT 250 WORDS)

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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.

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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.

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