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

Reconstituted high-density lipoproteins (rHDL) have been shown bind bacterial LPS and reduce its toxic effects. Since the effect of rHDL on LPS in vitro cannot be directly extrapolated to the in-vivo picture of Gram-negative septic shock, we have investigated the effects of rHDL in a rabbit model of Gram-negative bacteremia. Rabbits were anesthetized, ventilated, and invasively monitored for 6 hours. Escherichia coli (4 x 10(9) CFU/kg) were infused over 2 hours in rabbits given rHDL (75 mg/kg) before the bacterial challenge. Antibiotics were not used in this model. The bacterial infusion resulted in a bacteremia that persisted until the end of the study. The sepsis-induced TNF peak was significantly lowered by rHDL treatment (10 +/- 3 ng/mL in rHDL treated versus 33 +/- 5 in controls, P = 0.001). Blood pressure, although not statistically significant, tended to be higher in the rHDL group. Acidosis was significantly attenuated up to 3 hours after the beginning of the bacterial challenge (7.39 +/- 0.05 versus 7.27 +/- 0.05 in controls, P = 0.041). rHDL treatment produced some transient beneficial effects in this model of persistent Gram-negative bacteremia. Additional studies, investigating the effects of rHDL in combination with antibiotics, are warranted.
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PMID:Effects of reconstituted high-density lipoprotein in persistent gram-negative bacteremia. 861 60

Brain dysfunction is observed clinically in patients suffering from prolonged endotoxic shock. However, the etiology of brain dysfunction during sepsis is not clear. Certain researchers have reported that the decrease in brain catecholamines concentration during septic shock might be etiologically important in brain dysfunction. Therefore, we hypothesized that the beta-adrenergic receptor system undergoes a change during septic shock, and plays a role in the pathogenesis of septic encephalopathy. In this study, we examined two models of septic shock in rats, each of which has a different time course for the shock state. Male Wistar rats were divided into four groups: (1) Control--0.9% saline vehicle, (2) Lipopolysaccharide (LPS) i.v.-- Escherichia coli endotoxin 1.0 mg/ml i.v. bolus, (3) Sham-operated, and (4) Cecal ligation and puncture (CLP) model. The rats were killed by decapitation at 3, 12, or 24 hr after the treatments, and the brains were removed and subdivided into three areas: the forebrain, cerebellum, and brain stem. In the LPS i.v. group, the brain tissue norepinephrine (NE) concentration had decreased in the forebrain and brain stem and the tissue epinephrine (E) concentration had decreased in the brain stem by 3 hr after treatment. In the CLP group, the brain tissue NE concentration had decreased in the forebrain, cerebellum, and brain stem (P < 0.05), and the tissue E concentration had decreased in the forebrain and brain stem by 24 hr after treatment (P < 0.05). An alteration in beta-adrenergic receptor density in the forebrain was observed at 24 hr in the CLP group (control, 237.0 +/- 14.0 fmole/mg protein; LPS i.v., 233.2 +/- 3.0 fmole/mg protein; sham-operated, 236.0 +/- 3.0 fmole/mg protein; CLP, 177.0 +/- 4.2 fmole/mg protein). These alterations in transmitter concentrations and beta-adrenergic density in the forebrain may be an important factor in septic encephalopathy.
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PMID:Impairment of the brain beta-adrenergic system during experimental endotoxemia. 865 32

Nitric oxide can react with superoxide anion to form peroxynitrite. The resultant free radical can be rapidly protonated to yield even more toxic substances such as hydroxyl radical and nitric dioxide. The generation of either of these free radical species can promote lipid peroxidation and subsequent tissue injury if they are formed in excessive amounts. During sepsis, both nitric oxide synthesis and peroxynitrite production are substantially enhanced in a variety of tissues, effects which favor the development of lipid peroxidation. Consequently, this study was undertaken in conscious rats, to ascertain what effect lipopolysaccharide (LPS) has on inducible nitric oxide synthase expression in the small intestine and to determine whether this is associated with lipid peroxidation or morphologic injury. When examined by Western immunoblot analysis, significantly more inducible nitric oxide synthase immunoreactivity was detected in the ileum than in the jejunum 5 hr after treatment with intraperitoneal LPS (1 and 20 mg/kg). Further, using the thiobarbituric acid assay as an index of lipid peroxidation, it was demonstrated that significantly more thiobarbituric acid reactive substances were present in the ileal mucosa than in the jejunal mucosa after LPS (20 mg/kg) administration. However, LPS (20 mg/kg) resulted in morphologic damage to both segments of the intestinal epithelium. These data indicate that the gut is a target during sepsis and that regional differences exist within the small bowel with respect to induction of nitric oxide synthase and lipid peroxidation following LPS treatment. Thus, while induction of nitric oxide synthase during endotoxic shock may still represent a mechanism of local intestinal damage, it is not necessarily associated with enhanced lipid peroxidation.
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PMID:Effects of lipopolysaccharide on intestinal injury; potential role of nitric oxide and lipid peroxidation. 866 Nov 95

1. The cardiovascular failure in sepsis may result from increased nitric oxide biosynthesis, through the diffuse expression of an inducible nitric oxide synthase. In such conditions, nitric oxide synthase inhibitors might be of therapeutic value, but detrimental side effects have been reported with their use, possibly related to the blockade of constitutive nitric oxide synthase. Therefore, the use of selective inhibitors of inducible nitric oxide synthase might be more suitable. The aim of this study was to evaluate the effects of L-canavanine, a potentially selective inhibitor of inducible nitric oxide synthase, in an animal model of septic shock. 2. Anaesthetized rats were challenged with 10 mg/kg lipopolysaccharide intravenously. One hour later, they randomly received a 5 h infusion of either L-canavanine (20 mg h-1 kg-1, n = 15), nitro-L-arginine methyl ester (5 mg h-1 kg-1, n = 13) or 0.9% NaCl (2 ml h-1 kg-1, n = 21). Lipopolysaccharide induced a progressive fall in blood pressure and cardiac index, accompanied by a significant lactic acidosis and a marked rise in plasma nitrate. All these changes were significantly attenuated by L-canavanine, which also improved the tolerance of endotoxaemic animals to acute episodes of hypovolaemia. In addition, L-canavanine significantly increased survival of mice challenged with a lethal dose of lipopolysaccharide. In contrast to L-canavanine, nitro-L-arginine methyl ester increased blood pressure at the expense of a severe fall in cardiac index, while largely enhancing lactic acidosis. This agent did not improve survival of endotoxaemic mice. In additional experiments, we found that the pressor effect of L-canavanine in advanced endotoxaemia (4 h) was reversed by L-arginine, confirming that it was related to nitric oxide synthase inhibition. In contrast, L-canavanine did not exert any influence on blood pressure in the very early stage (first hour) of endotoxaemia or in the absence of lipopolysaccharide exposure, indicating a lack of constitutive nitric oxide synthase inhibition by this agent. 3. In conclusion, L-canavanine produced beneficial haemodynamic and metabolic effects and improved survival in rodent endotoxic shock. The actions of L-canavanine were associated with a selective inhibition of inducible nitric oxide synthase and were in marked contrast to the deleterious consequences of nitro-L-arginine methyl ester, a non-selective nitric oxide synthase inhibitor, in similar conditions.
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PMID:Beneficial effects of L-canavanine, a selective inhibitor of inducible nitric oxide synthase, during rodent endotoxaemia. 866 74

Small-volume resuscitation by means of bolus infusion of hypertonic saline solutions was first applied for the primary treatment of severe hemorrhagic and traumatic shock and promptly restored central hemodynamics and regional organ blood flow. Mechanisms of action are diverse--i. maintenance of high cardiac output (direct myocardial stimulation; increase in intravascular volume); ii. maintenance of peripheral arterial vasodilation (effect of hyperosmolality; plasma volume effect) and iii. reduction of tissue edema (shifting of tissue water along the osmotic gradient). These mechanisms promote the restoration of the severely impaired microcirculation frequently seen also in sepsis. Hypertonic volume therapy has been the object of several experimental studies of acute hyperdynamic endotoxemia, however, a greater number of clinical studies have to be developed for the better understanding of the positive, and perhaps hazardous, effects of small-volume resuscitation in sepsis and multiple organ failure. The aim of this paper is to review the concepts involving such solutions, and their potential use in treatment of profound hypovolemia and microcirculatory deterioration associated with sepsis and endotoxic shock.
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PMID:Hypertonic volume therapy: feasibility in the prevention and treatment of multiple organ failure and sepsis. 873 Dec 91

The effect of acute endotoxin-induced septic shock on myocardium oxidative stress after low or high vitamin C and/or E dietary supplementation was studied in guinea pigs, laboratory animals which, like human, do not have capacity for ascorbate synthesis. Neither the antioxidant enzymes or GSH were modified by endotoxin and vitamin treatments. Vitamin E showed a strong capacity to protect the myocardium against both enzymatic and non-enzymatic lipid peroxidation even in the presence of endotoxin. Vitamin C supplementation increased heart ascorbate whereas endotoxic shock totally depleted the heart ascorbate of vitamin C supplemented animals without changing vitamin E. Endotoxin significantly increased myocardium uric acid, a marker of ischemia induced oxidative stress, in animals fed with low vitamin C levels. This increase was totally prevented in vitamin C supplemented, but not in vitamin E supplemented animals. Strongly depressed levels of plasma vitamin C have been recently described in sepsis in human patients. The results suggest that ascorbate is a primary antioxidant target in the heart of endotoxin treated mammals lacking the capacity to synthesize ascorbate and that ascorbate can have a protective value against endotoxin-induced free radical damage in the myocardium. Implications of these results for the possible preventive role of vitamin C in humans during sepsis are discussed.
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PMID:Endotoxin depletes ascorbate in the guinea pig heart. Protective effects of vitamins C and E against oxidative stress. 876 Oct 15

Platelet activating factor (PAF) is a phospholipid mediator released upon stimulation of cells, such as mast cells, basophils, neutrophils, and macrophages, by opsonized agents. This mediator produces a variety of biological effects and acts via specific binding sites present on various cell types. This article briefly reviews the nature of PAF, as well as what is understood about its role in the inflammatory response associated with trauma, shock, and sepsis. Much of what is known of PAF biology and experimental pathophysiology has come from the discovery and subsequent use of selective PAF antagonists. In this respect, several of the PAF antagonists have been examined experimentally and some have been tested clinically in patients with sepsis and septic shock. Experimental and clinical studies suggest that PAF antagonists appear to be effective in cases of severe Gram-negative septic shock. Nonetheless, this mediator may not be a major component involved in the systemic inflammatory response syndrome.
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PMID:Platelet activating factor and its role in trauma, shock, and sepsis. 877 1

Sepsis is intricately associated with mesenteric ischemia. The remote complications of mesenteric ischemia are essentially those of sepsis, whether as a cause or as a consequence. Experimental endotoxic shock induces bowel hypoperfusion, erythrocyte extravasation and intestinal necrosis. The effects of pentoxifylline, rolipram and denbufylline, three phosphodiesterase inhibitors, were studied on endotoxin-induced bowel erythrocyte extravasation and intestinal and renal hypoperfusion, in conscious rats and anaesthetized dogs, respectively. Two hours after lipopolysaccharide i.v. injection in rats, erythrocyte extravasation was evident throughout the intestinal musculature and mucosa, apparently without affecting lungs, heart, kidneys, liver or pancreas. Pretreatment with the non-selective phosphodiesterase inhibitor, pentoxifylline, or selective phosphodiesterase IV inhibitors such as denbufylline or rolipram reduced intestinal haemoconcentration. In the anaesthetized dog, pentoxifylline and denbufylline both inhibited the E. coli lipopolysaccharide-induced mesenteric blood flow fall, without affecting renal blood flow or cardiac index. In conclusion, phosphodiesterase inhibitors protected from intestinal damage and bowel hypoperfusion after lipopolysaccharide challenge. This action may thus play a role in the protective effects against endotoxin-induced lethal toxicity previously described for phosphodiesterase inhibitors.
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PMID:Inhibition of lipopolysaccharide-induced bowel erythrocyte extravasation in rats, and of mesenteric hypoperfusion in dogs, by phosphodiesterase inhibitors. 890 Oct 18

Sepsis and septic shock continue to have a high mortality and morbidity in the newborn. Eicosanoids are important mediators in Gram negative septic shock. Omega-3 polyunsaturated fatty acids (omega-3) decrease production of biologically active 2-series eicosanoids. Therefore, we hypothesized that omega-3-enriched diet could decrease 2-series eicosanoids and attenuate endotoxic shock in newborn rats. Sprague-Dawley rat dams were fed with either omega-3 polyunsaturated fatty acid-enriched diet (omega-3 PURA) or omega-6 polyunsaturated fatty acid enriched diet (omega-6PUFA; controls) from the 16th day of gestation until 10 days after parturition. In 10 day old rats, shock was induced by an intraperitoneal injection of Salmonella enteritidis lipopolysaccharide. The omega-3PUFA decreased the mortality of endotoxic shock. In omega-6PUFA, lipopolysaccharide induced hyperglycemia at 2 h and hypoglycemia thereafter without an elevation in plasma insulin concentration, omega-3PUFA attenuated the hyperglycemia and hypoglycemia. omega-3PUFA attenuated the decrease of liver phosphoenolpyruvate ca-boxykinase mRNA abundance, suggesting preserved gluconeogenesis. Therefore, perinatal feeding with omega-3PUFA was beneficial in attenuating glucose dyshomeostasis in newborn rats with endotoxic shock and may be a novel approach to the prevention of endotoxic shock in the newborn.
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PMID:Perinatal nutrition enriched with omega-3 polyunsaturated fatty acids attenuates endotoxic shock in newborn rats. 890 43

beta-2-Adrenergic agents can increase mesenteric blood flow under normal conditions. However, the effects of dobutamine on regional blood flow in sepsis are less well defined since diverging results had been obtained in some studies due to the differences in animal models. In this fluid-resuscitated hyperdynamic endotoxic dog model, we studied the effects of dobutamine on mesenteric, renal, and femoral perfusion. Twenty-one dogs were anesthetized with pentobarbital and paralyzed. Cardiac output was determined by thermodilution, whole body oxygen consumption (VO2) by indirect calorimetry, and regional blood flow by electromagnetic flow probes. Gut tonometry was also assessed. After 2 mg/kg endotoxin administration, the dogs were randomized to receive fluids (to achieve a pulmonary artery balloon-occluded pressure around 10 mm Hg) either alone (n = 7) or combined with a dobutamine infusion at a rate of 5 microgram/kg x min (n = 7) or 10 microgram/kg x min (n = 7). After fluid resuscitation, cardiac index increased (from 57 +/- 28 to 258 +/- 112 ml/kg x min, P < 0.001) but then slightly decreased with time in the control group, but further increased (to 436 +/- 85 ml/kg x min, P < 0.001) and remained elevated in the dobutamine-treated animals. Whole body oxygen delivery (DO2) followed a similar course. Whole body VO2 increased after endotoxin and fluid resuscitation (from 4.9 +/- 1.3 to 6.3 +/- 1.1 ml/kg x min, P < 0.01), especially in the dobutamine-treated animals (to 6.7 +/- 2.1 ml/kg x min, P < 0.01). Mesenteric DO2 increased after fluid administration (from 11.6 +/- 6.7 to 56.3 +/- 31.9 ml/min, P < 0.01) and further increased with dobutamine (to 91.7 +/- 42.5 ml/min, P < 0.01). It decreased with time in all groups. Mesenteric VO2 remained unchanged but gastric intramucosal pH (pHi) continuously decreased with time in the control group (from 7.41 +/- 0.24 to 6.80 +/- 0.17, P < 0.01) while dobutamine prevented the decrease in pHi (7.08 +/- 0.29). Renal DO2 and renal VO2 decreased with time slightly and similarly in the three groups (from 34.8 +/- 13.8 to 22.9 +/- 10 ml/min and 4.0 +/- 1.6 to 2.8 +/- 1.0 ml/min, respectively) but urine output increased only in the dobutamine-treated animals (from 2.0 +/- 1.5 to 6.9 +/- 7.0 ml/min, P < 0.01). Femoral DO2 decreased with time in the control groups but increased in the dobutamine-treated animals. Femoral VO2 remained stable. No statistical differences were found between 5 and 10 microgram/kg x min dobutamine. In this hyperdynamic endotoxic shock model, administration of a limited dose of dobutamine could be useful to increase mesenteric blood flow and urine output.
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PMID:Regional effects of dobutamine in endotoxic shock. 890 53


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