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Query: UMLS:C0036690 (sepsis)
 59,461 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The acute metabolic response following experimentally induced sepsis can generally be classified as either hypodynamic ("low flow") or hyperdynamic ("high flow"). We have found that in conscious guinea pigs the bolus infusion of 10(10) live Escherichia coli bacteria can elicit either response, depending on the route of administration of the bacteria. Intravenous infusion results in the hypodynamic condition of septic shock in which oxygen consumption (VO2) is reduced to approximately 60% of the control level, plasma glucose is elevated 4 hr after infusion with a reversal to extreme hypoglycemia 12 hr after infusion, and body temperature is reduced by approximately 5 degrees C in 12 hr. In contrast, subcutaneous injection results in increased VO2, body temperature, and plasma glucose. In both models the concentration of cortisol, catecholamines and glucagon were elevated, but the responses were more pronounced in the hypodynamic model. In both cases, insulin concentration was decreased. These models of sepsis are useful because many aspects of response are comparable to man, they are simple to create, and they are consistent and reproducible.
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PMID:Hyper and hypodynamic models of sepsis in guinea pigs. 249 5

The effect of administered human growth hormone (hGH) on protein metabolism in septic rats was investigated. Fifty-three male Wistar rates with SVC cannulation were divided into four groups. Group I (n = 10) underwent sham-operation. Sepsis was induced by cecal ligation in group II (n = 19), group III (n = 10), and group IV (n = 14). Isocaloric, isonitrogenous glucose/amino acids were infused for 4 days. hGH was administered in group III (100 mU/day) and group IV (200 mU/day) every day. Cumulative nitrogen balance (mg/kg) in group IV was significantly higher than in group II (p less than 0.01): group I, 1264 +/- 355; group II, 117 +/- 693; group III, 92 +/- 735; group IV, 1001 +/- 279. Cumulative urinary excretion of 3-methylhistidine (3-MH, mg/kg) did not differ between group II and group IV: group I, 6.2 +/- 0.9; group II, 12.0 +/- 2.2; group III, 13.4 +/- 2.9; group IV, 10.5 +/- 2.3. Serum albumin level in group IV (1.8 +/- 0.2 g/dl) was significantly higher than in group II (1.5 +/- 0.2 g/dl) (p less than 0.01). Blood urea nitrogen level in group IV (12.6 +/- 2.3 mg/dl) was significantly lower than in group II (18.8 +/- 7.4 mg/dl) (p less than 0.05). Although serum levels of glucose, insulin, triglyceride, and phospholipid were higher in sepsis groups than in sham-operated group, those levels did not differ among sepsis groups. Administration of hGH, 200 mU/day, resulted in marked nitrogen retention and had little effect on 3-MH excretion.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Effect of administered human growth hormone on protein metabolism in septic rats. 251 84

The insulin stimulatory effect of 7 mM glucose on isolated perifused rat islets is dramatically potentiated by the monokine interleukin 1 (IL-1). At levels (10(-10) -10(-8) M) noted in vivo during sepsis, it reversibly amplifies peak second phase insulin release to the hexose. At 2.75 mM glucose, however, IL-1 has no effect on insulin secretion. IL-1 also potentiates glyceraldehyde (2 mM)- and alpha-ketoisocaproate (5 mM)-induced insulin secretion. In islets whose phosphoinositides were prelabeled with myo-[2-3H]inositol, 2.0-5.0 nM IL-1 increases the efflux of [3H]inositol from subsequently perifused islets, the parallel accumulation of labeled inositol phosphates, and insulin secretion in the simultaneous presence of 7 mM glucose but not 2.75 mM glucose. In support of these in vitro observations, the in vivo infusion of IL-1 (40 micrograms/kg body wt) elevated circulating plasma insulin levels two-to fourfold. These results establish IL-1 as a potent, readily reversible, glucose-dependent modulator of stimulated insulin secretion and further suggest that its positive impact on insulin release is mediated, at least in part, by phosphoinositide-derived second messenger molecules. IL-1-induced insulin secretion may participate in the multiple metabolic and immunologic adaptations occurring during sepsis.
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PMID:Interleukin 1 is a potent stimulator of islet insulin secretion and phosphoinositide hydrolysis. 253 31

Although adequate volume resuscitation has decreased mortality from hemorrhagic shock, recovery in many patients is complicated by sepsis. To determine whether a subject debilitated by hemorrhagic shock would exhibit greater cardiocirculatory dysfunction when challenged with sepsis, ten dogs (Group I) were hemorrhaged to a mean arterial blood pressure of 30 mm Hg. After 2 hours of hypotension, shed blood and lactated Ringer's solution (50 ml/kg) were given, and the dogs were observed for 3 to 6 days. Ten dogs were sham hemorrhage and served as controls (Group II). On the experimental day, all cardiovascular and hemodynamic parameters were measured in both groups of animals before endotoxin challenge. There was no significant difference in cardiac output, stroke volume, stroke work, +dP/dt max, myocardial blood flow, myocardial oxygen metabolism, or acid-base balance in the two groups. Compared to sham-hemorrhaged dogs, resuscitated shock dogs had a significantly lower mean arterial blood pressure (127 +/- 7 vs. 110 +/- 6 mm Hg; p less than 0.05), and heart rate was significantly higher (86 +/- 6 vs. 109 +/- 7 beats/minute; p less than 0.05). Furthermore, maximal rate of left ventricular pressure fall (-dP/dT max) was significantly lower in the animals previously hemorrhaged, suggesting a persistent defect in left ventricular relaxation. Blood glucose and insulin levels were significantly elevated in the resuscitated shocked dogs, likely due to increased circulating catecholamine concentrations and enhanced glycogenolysis. Endotoxin shock caused significant hypotension, acidosis, and impaired regional perfusion in all dogs. In addition, cardiac output, stroke volume, dP/dT, and left ventricular end-diastolic pressure fell and hyperglycemia and hyperinsulinemia occurred in all dogs after endotoxin injection.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:The cardiocirculatory and metabolic effects of endotoxin challenge after canine resuscitated hemorrhagic shock. 256 78

The plasma concentration of various catabolic hormones, including glucagon and catecholamines, is elevated in sepsis. Furthermore, the infusion of these hormones into control animals increases the rate of glucose production. Previous studies by our laboratory have demonstrated that adrenergic blockade alone is not able to reverse or prevent the sepsis-induced increase in glucose metabolism. Therefore, the purpose of the present study was to determine whether the sepsis-induced hyperglucagonemia was important to maintain the elevation in glucose metabolism. Hypermetabolic sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of Escherichia coli. Glucose kinetics, assessed by the constant i.v. infusion of [6-3H]- and [U-14C]-glucose, were determined in septic and nonseptic rats prior to and for 3-4 hr after the infusion of somatostatin with or without insulin replacement. Sepsis increased the rate of glucose appearance (80%), recycling (276%), and metabolic clearance (88%), as well as the plasma lactate concentration (140%), compared to nonseptic rats. Lowering both the insulin and glucagon concentration with somatostatin did not attenuate the sepsis-induced increases in glucose metabolism. However, when the hyperglucagonemia was selectively reduced by replacing insulin, and euglycemia was maintained by a glucose infusion, the elevated rate of endogenous glucose production returned to levels not different from nonseptic animals. In contrast, the sepsis-induced elevation of glucose clearance was unaltered under these conditions. These results indicate that during hypermetabolic sepsis the elevated glucagon level is an important mediator of the enhanced rate of gluconeogenesis.
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PMID:Importance of hyperglucagonemia in eliciting the sepsis-induced increase in glucose production. 257 79

To assess the effect of sepsis on ketone body (KB) kinetics in humans, we measured in normal and septic subjects KB appearance rate (Ra) before (initial state) and during a rise of free fatty acids (FFA) level (intravenous infusion of a triglycerides emulsion). We studied normal subjects in postabsorptive state and septic patients when receiving an hypocaloric intravenous infusion of glucose and amino acids or 12 h after its interruption. When receiving glucose and amino acids infusion, septic patients had higher glucose and insulin levels than normal subjects, and despite lower FFA concentrations (255 +/- 44 vs. 480 +/- 51 mumol/l, P less than 0.05) comparable initial KB Ra (2.50 +/- 0.10 vs. 2.48 +/- 0.30 mumol.kg-1.min-1). Triglyceride infusion increased FFA to comparable values (septic 780 +/- 130, normal 730 +/- 45 mumol/l), but KB Ra rose in septic patients only to 3.7 +/- 1.1 instead of 7.7 +/- 1.1 mumol.kg-1.min-1 as in normal subjects (P less than 0.05). Somatostatin infusion decreased the hyperinsulinemia of septic patients but did not restore a normal ketogenesis. After interruption of nutriment infusion, septic patients had normal FFA levels and only mild hyperglycemia and hyperinsulinemia. Their initial KB Ra was not modified. However, their response of KB Ra (increase to 6.27 +/- 2.0 mumol.kg-1.min-1) to raised FFA levels (842 +/- 170 mumol/l) was comparable to the response of normal subjects. In conclusion, although septic patients receiving an hypocaloric parenteral nutrition had a depressed ketogenesis they were able to restore a normal ketogenic capacity after a short-time caloric deprivation. Glucose and/or insulin appears to have a major role in this modulation of hepatic ketogenesis.
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PMID:Regulation of ketone body flux in septic patients. 259 97

Hypoglycemia associated with renal failure is more common than generally thought. Its occurrence is often a marker of multisystem failure and has an ominous prognostic implication. Its pathogenesis is frequently complex and involves one or several mechanisms. In the evaluation of uremic hypoglycemia, the first step should be the exclusion of obvious causes such as insulin, oral hypoglycemic agent therapy, and the use of drugs known to cause hypoglycemia. Propranolol, salicylates, and disopyramide are among the most commonly implicated agents. Additional triggering events are alcohol consumption, sepsis, chronic malnutrition, acute caloric deprivation, concomitant liver disease, congestive heart failure, and an associated endocrine deficiency. When no obvious cause can be demonstrated, the hypoglycemia is referred to as spontaneous. Spontaneous uremic hypoglycemia has been attributed to deficiency of precursors of gluconeogenesis, that is, alanine, deficient gluconeogenesis, impaired glycogenolysis, diminished renal gluconeogenesis and impaired renal insulin degradation and clearance, poor nutrition, and, in a few cases, deficiency in an immediate counterregulatory hormone such as catecholamine and glucagon. However, the mechanism(s) seems to differ from one patient to the other. Dialysis also predisposes to hypoglycemia in uremia, possibly because of the chronic state of malnutrition. Postdialysis hypoglycemia is secondary to glucose-induced hyperinsulinemia, which is caused by the high glucose content in the dialysate. In uremic hypoglycemia, neuroglycopenic manifestations predominate because of frequent autonomic nervous system dysfunction and lack of catecholamine release in response to hypoglycemia. Its severity and duration are variable. Hypoglycemia should be suspected in any patient with renal failure who exhibits any change in mental or neurologic status. Detection of hypoglycemia should rely on frequent and careful glucose determinations in any patient with uremia.
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PMID:Hypoglycemia associated with renal failure. 264 22

1. Sepsis induced by caecal ligation and puncture increased the rates of hepatic cholesterogenesis and fatty acid synthesis in vivo compared with sham-operated rats. These changes were accompanied by higher concentrations of lactate and pyruvate in blood and liver and an increase in plasma insulin. 2. The total activity of hydroxymethylglutaryl-coenzyme A (HMG-CoA) reductase (EC 1.1.1.88) in liver was increased by sepsis, but there was no significant change in the expressed activity. Short-term insulin deficiency (induced by mannoheptulose or streptozotocin) decreased the rates of cholesterogenesis and fatty acid synthesis in livers of septic rats but did not alter the expressed/total activity of HMG-CoA reductase. 3. It is concluded that the increased rate of hepatic cholesterogenesis in septic rats is in part a result of the higher plasma insulin, the hormone acting to maintain the total activity of HMG-CoA reductase and to stimulate a step before the formation of HMG-CoA. 4. These changes may contribute to the hypertriacylglycerolaemia associated with sepsis.
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PMID:Increased rates of hepatic cholesterogenesis and fatty acid synthesis in septic rats in vivo: evidence for the possible involvement of insulin. 264 66

The present study was performed to determine whether hypermetabolic sepsis alters peripheral and hepatic insulin sensitivity and/or responsiveness. Nonlethal sepsis was produced in chronically catheterized conscious rats by repeated subcutaneous injections of live Escherichia coli. Basal glucose metabolism was determined using a primed-constant infusion of [3-3H]glucose initiated 20 hr after the first injection of bacteria. Thereafter, in vivo insulin action was assessed using the euglycemic hyperinsulinemic clamp technique. Insulin was infused at various rates in separate groups of animals for 3 hr to produce steady-state insulin levels of approximately 60, 120, 400, 2,500, and 25,000 microU/ml, and euglycemia was maintained by varying the glucose infusion rate. The sepsis-induced hyperglucagonemia was not significantly altered by the infusion of insulin and glucose. In septic rats, the dose-response curve for the insulin-induced increment in glucose utilization was shifted downward and to the right. As a result, septic rats showed a twofold increase in the ED50 value (380 vs. 190 microU/ml) and a 50% reduction in the maximal responsiveness compared with control animals, indicating peripheral insulin resistance. Septic and nonseptic animals, however, had a similar reduction in the endogenous glucose production rate as the plasma insulin concentration was increased, suggesting that there was no hepatic insulin resistance. The plasma lactate concentration increased in a dose-dependent manner in both septic and nonseptic rats as the plasma insulin concentration was raised. However, the increment in steady-state lactate concentration was consistently higher (75-220%) in septic animals at each insulin infusion rate. These results indicate that nonlethal hypermetabolic sepsis in the rat is associated with peripheral insulin resistance.
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PMID:In vivo insulin resistance during nonlethal hypermetabolic sepsis. 266 Oct 48

Proteolysis is increased in sepsis, but it is not known whether myofibrillar and non-myofibrillar proteins are broken down in the same fashion, or respond to the same regulatory forces as in non-septic muscle. In this study, therefore, the effect of sepsis on total and myofibrillar protein breakdown in incubated rat extensor digitorum longus (EDL) and soleus (SOL) muscles was determined, and the response in vitro to different concentrations of insulin (10 to 10(5) microU/mL) of protein degradation was studied in incubated EDL muscles from control and septic rats. Sepsis was induced in rats weighing 40 to 60 g by cecal ligation and puncture (CLP). Control animals were sham operated. Sixteen hours after CLP or sham operation, intact EDL and SOL muscles were incubated for two hours in oxygenated Krebs-Henseleit bicarbonate buffer containing glucose (10 mmol/L) and cycloheximide (0.5 mmol/L), and total and myofibrillar protein breakdown was assessed from release into incubation medium of tyrosine and 3-methylhistidine (3-MH), respectively. Tyrosine and 3-MH were determined fluorometrically by high performance liquid chromatography (HPLC). Tissue levels of tyrosine and 3-MH remained stable both in control and septic muscles during incubation for two hours. The rate of tyrosine release was increased during sepsis by 58% (P less than .001) and 15% (NS) in EDL and SOL muscle, respectively. The corresponding figures for 3-MH were 103% (P less than .001) and 21% (NS). Tyrosine release was reduced by insulin at a concentration of 10(3) microU/mL in control muscle and at a concentration of 10(4) microU/mL in septic muscle.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Total and myofibrillar protein breakdown in different types of rat skeletal muscle: effects of sepsis and regulation by insulin. 266 65


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