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

Surgical management of extrahepatic cholestasis is frequently complicated by sepsis, which can be explained in part by diminished function of the reticuloendothelial system. We have explored the possibility that the metabolic response to infection may also be abnormal. Fischer 344 rats underwent either bile duct ligation (BDL) or sham operation and were studied 3 days after operation. Hepatic amino acid uptake measured in vivo by the accumulation of 14C-alpha-aminoisobutyric acid or in vitro by the rate of transport of 14C-alanine by isolated hepatocytes was unaltered in the BDL animals, while gluconeogenesis from alanine by viable hepatocytes from BDL rats was actually enhanced. However, the expected increase in hepatic amino acid uptake in response to endotoxin was diminished in the BDL animals. In addition, we observed impaired responses of the jaundiced animals to glucagon and interleukin-1, two mediators of the hepatic acute phase response to endotoxin. These data suggest that while hepatic amino acid transport is normal in the basal state, the rat with extrahepatic biliary obstruction does not respond appropriately to stress and that this defect cannot be explained solely on the basis of altered handling of endotoxin by the reticuloendothelial system.
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PMID:Impaired metabolic response to endotoxin in obstructive jaundice. 352 8

Rats were treated with Escherichia coli endotoxin (ET) either acutely or chronically or rendered septic by cecal ligation and puncture. At 6 h after ET injection, at various intervals of continuous ET infusion, and at 17-18 h after the onset of peritonitis, animals were killed and hepatocytes were isolated. Cytosolic [Ca2+] ([Ca2+]c) was measured by quin 2 during the resting state and after stimulation with epinephrine and vasopressin. Basal and epinephrine-, vasopressin- and glucagon-stimulated glycogen phosphorylase activity were also determined. In hepatocytes from acutely ET-treated rats, resting levels of [Ca2+]c were decreased 46% from 245.8 +/- 11.0 to 131.0 +/- 8.5 nM (n = 4-6, P less than 0.05). In septic rats a 39.5% decrease was noted [i.e., from 154.0 +/- 17.7 (n = 4, sham) to 93.3 +/- 91 nM (n = 5, septic, P less than 0.05)]. These decreased [Ca2+]c levels were associated with changes of glycogen phosphorylase activity in a manner suggesting a cause and effect relationship; e.g., acute ET treatment resulted in greater than 80% depression of phosphorylase a activity, whereas sepsis induced a 58% decrease in the activity of this enzyme. In ET-infused rats the resting level of [Ca2+]c and its response to hormonal stimulation were not different from hepatocytes of saline-infused rats, although glycogen phosphorylase activity was less responsive to these hormones. The effect on the enzyme's response to Ca2+-mobilizing hormones was more marked than to glucagon. This is consistent with the concept that information flow in the Ca2+-messenger system is a site of metabolic lesions produced by endotoxicosis and sepsis.
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PMID:Rat liver free cytosolic Ca2+ and glycogen phosphorylase in endotoxicosis and sepsis. 353 41

Elevated plasma levels of the so-called catabolic hormones (glucocorticoid, epinephrine, glucagon) have been observed in severely injured patients, and infusion of these hormones to normal subjects has reportedly simulated several metabolic aberrations characteristic of severe trauma and sepsis. We recently reported that amino acid uptake was reduced in soleus muscle, heart, and diaphragm, and increased in the liver, of septic rats. The purpose of the present study was to investigate organ amino acid uptake in nonseptic rats infused with catabolic hormones. Central venous catheters were placed in male Sprague-Dawley rats (100-150 g) and after 24 hr hormones (glucagon 5 micrograms/kg/hr, epinephrine 6 micrograms/kg/hr, corticosterone 4.2 mg/kg/hr) or vehicle (saline, ascorbic acid 1 mg/ml, albumin 3 mg/ml) was infused for 72 hr. Animals were housed in metabolic cages and allowed food and water ad lib. One hour prior to sacrifice, alpha-[3H]aminoisobutyric acid (AIB) (2.5 microCi), a nonmetabolized amino acid analog mainly transported by system-A, was injected intravenously. Animals were killed and organs were removed, weighed, and dissolved in tissue solubilizer for measurement of radioactivity. AIB uptake was significantly elevated in all organs of catabolic hormone-infused animals studied. The results suggest that catabolic hormones may be involved in the pathogenesis of increased amino acid uptake in the liver during sepsis. Inhibited amino acid uptake in skeletal muscle during sepsis, however, is probably not primarily mediated by catabolic hormones.
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PMID:Effect of catabolic hormone infusion on organ amino acid uptake. 357 67

To determine whether alterations in hepatocyte membrane electrical responses might play a role in glucose dyshomeostasis during sepsis, hepatocyte membrane potentials were measured in vivo in rats made septic by cecal ligation and puncture (CLP). In both early-septic (8-10 hr after CLP) and late-septic (18-20 hr after CLP) rats, resting hepatocyte membrane potentials were significantly depressed compared to those in sham-operated rats. In addition, the hyperpolarization response to glucagon administration in vivo which was observed in the sham-operated rats was significantly attenuated in both early- and late-sepsis rats. To determine whether this blunted hyperpolarization response was related to defects in stimulation of gluconeogenesis, livers from sham-operated and early-sepsis rats were isolated and perfused. The livers from sham-operated rats responded to 1 nM glucagon by increasing glucose release by 53%, while those from septic rats increased by only 20%. These results suggest that a defect associated with the plasma membrane may be an early event in the development of glucose dyshomeostasis during sepsis.
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PMID:Alterations in hepatic membrane potentials in vivo during early and late sepsis. 360 2

We have assessed the role of glucagon and sympathetic nervous system (SNS) activity on glucose and palmitate kinetics and oxidation in the conscious dog infused with live Escherichia coli bacteria by means of the simultaneous primed constant infusion of [1,2-13C]palmitate and [U-14C]-glucose. The basal rate of glucose production in septic dogs and controls was similar. However, when the glucagon concentration was selectively decreased in the septic animals by the appropriate infusion of somatostatin (S), insulin (I), and glucagon (G), the rate of glucose production decreased significantly, whereas in control animals S + I + G infusion had no effect on glucose kinetics. When alpha- and beta-adrenergic blockade was added to the infusion, the rate of glucose production decreased further and hypoglycemia developed in the septic dogs, whereas in the controls both glucose production and concentration increased. The basal rate of appearance of palmitate was increased in the septic dogs (P less than 0.01). S + I + G had no effect on palmitate appearance in either group, and sympathetic blockade caused a significant decrease in palmitate appearance in both groups of dogs. The rates of oxidation of both glucose and palmitate was related directly to their availability in plasma. Thus, in sepsis, glucagon and SNS activity play important roles in the mobilization of glucose and palmitate into the plasma and therefore in the overall state of energy metabolism.
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PMID:Glucose and FFA kinetics in sepsis: role of glucagon and sympathetic nervous system activity. 388 89

The effect of gram-negative sepsis on the kinetics and oxidation of very low-density lipoprotein (VLDL) fatty acids was assessed in conscious dogs in the normal state and 24 h after infusion of live Escherichia coli. VLDL, labeled with [2-3H]glycerol and [1-14C]palmitic acid, was used to trace VLDL kinetics and oxidation, and [1-13C]palmitic acid bound to albumin was infused simultaneously to quantify kinetics and oxidation of free fatty acid (FFA) in plasma. Sepsis caused a fivefold increase in the rate of VLDL production (RaVLDL). In the control dogs, the direct oxidation of VLDL-fatty acids was not an important contributor to their overall energy metabolism, but in dogs with sepsis, 17% of the total rate of CO2 production could be accounted for by VLDL-fatty acid oxidation. When glucose was infused into dogs with insulin and glucagon levels clamped at basal levels (by means of infusion of somatostatin and replacement of the hormones), RaVLDL increased significantly in the control dogs, but it did not increase further in dogs with sepsis. We conclude that the increase in triglyceride concentration in fasting dogs with gram-negative sepsis is the result of an increase in VLDL production and that the fatty acids in VLDL can serve as an important source of energy in sepsis.
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PMID:Effect of sepsis on VLDL kinetics: responses in basal state and during glucose infusion. 389 May 59

Controversy exists in the literature concerning the effects of insulin and glucagon on cardiac muscle contractility, in particular during anoxia, ischemia or sepsis. The purpose of the present study was to determine the effects of insulin and glucagon on the systolic function of the normal and the dysfunctioning septic rat myocardium in the Langendorff preparation. In the normal isolated rat heart, neither insulin nor glucagon exhibited any lasting inotropic effect on systolic function or coronary flow. Sepsis (cecal ligation and puncture) resulted in a dramatic reduction of systolic function to 44% of control animals. All insulin-containing formulations tested improved systolic function in septic hearts by a mean of 85% compared to Krebs and glucose only. However, this improvement did not reach statistical significance compared to the use of Krebs and glucose only. Glucagon at 100 micrograms/l was doing as well as Krebs and glucose alone while at 1 mg/l glucagon was only able to maintain pre-perfusion contractility. Our results suggest that neither insulin nor glucagon seem to possess special inotropic properties for the isolated perfused normal or septic rat heart.
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PMID:The effect of insulin and glucagon on systolic properties of the normal and septic isolated rat heart. 390 99

We postulate that high plasma concentrations of gastrointestinal-derived glucagon may be used to identify severe sepsis and correlate with the effect of therapy. Eighteen adult dogs were separated into three groups: Group I-LD100 E. coli alone, group II-LD100 E. coli + tobramycin (TOB) and group III-LD100 E. coli + TOB + methylprednisolone sodium succinate (MPSS). E. coli was infused intravenously for one hour. Each animal was monitored for six hours and observed for a 7-day recovery period. Percent survival (greater than 7 days): I = 0%, II = 17% and III = 83%. Concentrations of gastrointestinal glucagon were 3417 pg/ml in group I, 5167 pg/ml in group II and 1081 pg/ml in group III at six hours after E. coli infusion. In group III these concentration returned to control values by 7 days after E. coli infusion. Increases in gastrointestinal glucagon were more readily induced by E. coli infusion than those of pancreatic glucagon. Gastrointestinal glucagon concentrations were related to the severity of E. coli induced shock and the beneficial effects of MPSS/TOB therapy. Therefore, plasma gastrointestinal glucagon concentrations may be useful in recognizing the presence of severe sepsis and directly related to the beneficial effects of therapy.
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PMID:[Studies of plasma gastrointestinal glucagon after LD100 E. coli infusion]. 391 Oct 50

Recent reports from our laboratory and others have documented changes in insulin unresponsiveness and electrolyte and hormonal changes characteristic of hypodynamic shock states in anesthetized animals. Since most acute shock protocols do not adequately mimic the clinical profile of sepsis, the present study was undertaken to document the hemodynamic and metabolic changes associated with chronic hyperdynamic peritonitis in dogs. Mongrel dogs of either sex weighing 20 +/- 2 kg were surgically instrumented with an electromagnetic aortic flow probe for monitoring cardiac output determinations, and aortic and central venous catheters for withdrawing blood for blood pressure and chemical analyses. Following a recovery period (7-10 days) control hemodynamic and metabolic measurements were made. Sepsis was induced (peritoneal abscess) by implanting a 4" X 4" gauze sponge, previously inoculated with human fecal bacteria, amid the intestines. Experimental (N = 18) and pair-fed control (N = 6) animals were monitored daily for 21 days or until death. During the septic protocol, cardiac index increased from a control value of 3.4 L/min/m2 to 5.5 L/min/m2 by the end of the experimental period. Mean arterial blood pressure, total peripheral resistance index, body weight, and plasma Ca++ fell below control values during the experimental period. Body temperature, plasma glucose, insulin, glucagon, and Mg++ were all elevated with sepsis. At the end of the chronic experimental period, skeletal muscle insulin responsiveness was assessed in the isolated, innervated, constantly perfused gracilis muscle preparation. Pair-fed control animals responded to various concentrations of local insulin infusion by increasing glucose uptake by the gracilis muscle. However, septic animals had a blunted response to local insulin infusion resulting in a decrease in the maximum dose response effect. These data demonstrate that: chronic, hyperdynamic peritonitis in the dog more closely mimics the human clinical profile of sepsis; and hyperdynamic sepsis is associated with a state of skeletal muscle insulin unresponsiveness which results from a post-receptor defect.
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PMID:Skeletal muscle insulin unresponsiveness during chronic hyperdynamic sepsis in the dog. 403 10

We have investigated the response of glucose and free fatty acid (FFA) kinetics and oxidation to betahydroxybutyrate (BOHB) infusion (30 mumol/kg X min) in both normal and Escherichia coli septicemic conscious dogs. In both the septic and control groups, experiments were performed in which hormone levels were allowed to change in response to the BOHB infusion, and in which the infusion of somatostatin, insulin, and glucagon were used to hold those hormone levels constant and sympathetic activity was blocked by the infusion of propranolol and phentolamine. In the nonseptic groups, the infusion of BOHB decreased both glucose production and FFA appearance (RaFFA) independent of the hormonal status. Glucose oxidation decreased in proportion to the decrease in production and uptake. FFA oxidation decreased only when hormones were controlled. In contrast, the infusion of BOHB in septic dogs did not suppress either glucose production or RaFFa, irrespective of the hormonal status. Substrate oxidation again corresponded to the rate of appearance of the substrate. We conclude that in normal dogs, ketones act directly as metabolic regulators to decrease the appearance of both glucose and FFA in the plasma, but do not directly affect the ability of the animal to oxidize these substrates. In sepsis, the normal regulatory actions of ketones appear to be lost.
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PMID:Energy and substrate kinetics and oxidation during ketone infusion in septic dogs: role of changes in insulin and glucagon. 614 25


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