Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Extremity tourniquets are widely used to achieve bloodless dissection in the surgical field. Excision of venous stasis ulcers (VSU) is aided by tourniquet use because of large dilated veins associated with venous stasis disease. We present 3 patients with hypotensive shock occurring 10 to 15 minutes after tourniquet release after excision of venous stasis ulcers. All patients had long histories of venous stasis changes and two-thirds had prior histories of deep vein thromboses and pulmonary embolism. Mean tourniquet inflation time was 34 minutes and there were electrocardiographic changes in two-third of the patients. All patients responded rapidly to standard resuscitation measures and in all 3 postoperative testing for pulmonary embolus and myocardial infarction was negative. Wound cultures revealed no organisms in 1 patient, mixed Gram-positive cocci in another, and greater than 10(5) Serratia marcescens in the third patient. Although small decreases in blood pressure and blood pH, and increases in blood lactate, PcO2, and creatinine phosphokinase, are normally associated with the use of extremity tourniquets, hypotensive shock has not been reported. The combined effect of tourniquet ischemia and venous stasis changes may cause hypotensive shock by (1) an endotoxic bolus upon tourniquet release, (2) pulmonary microembolization of platelet, fibrin, and leukocyte aggregates causing vasoactive substance release, and (3) synergistic effects of platelet-activating factor, a known mediator of endotoxic shock. The untoward events noted in these patients may be prevented by (1) proximal to distal dissection of the ulcer with initial ligation of large veins, (2) pretreatment with steroids and/or platelet-activating factor antagonists, and/or (3) slow release of the tourniquet.
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PMID:Tourniquet-related hypotension in venous stasis ulcer excision. 836 87

We investigated the mechanisms by which endotoxic shock induces intrinsic myocardial depression by studying cardiac myocytes isolated from 10 anesthetized instrumented rabbits given 172 +/- 42 (mean +/- SD) micrograms/kg IV endotoxin. Left ventricular (LV) depression developed 4 +/- 1 hours after endotoxin administration, with a 15 +/- 4% increase in LV internal end-systolic diameter, measured with sonomicrometers at a matched LV end-systolic pressure of 65 +/- 10 mm Hg. Normal LV pressure, arterial PO2, and pH were maintained to minimize confounding effects of ischemia, hypoxia, and acidosis. Cardiac myocytes from endotoxin-exposed rabbits had less unloaded cell shortening and lower peak rates of cell shortening (-dL/dt) and lengthening (+dL/dt) at [Ca2+] levels ranging from 0.5 to 16 mM when compared with myocytes isolated from normal rabbits or rabbits undergoing an identical protocol but without exposure to endotoxin. At 2 mM [Ca2+], cell shortening was depressed by approximately 25% because of a decrease in action potential duration (207 +/- 70 versus 375 +/- 64 milliseconds). In contrast, there was only mild impairment of sarcoplasmic reticulum (SR) function. When myocytes were restimulated after rest periods of 4 to 480 seconds, the decrement in cell shortening (rest decay), peak -dL/dt and peak +dL/dt, and the recovery from rest decay were similar in myocytes from endotoxin-treated and normal rabbits. There was a greater decrement in cell shortening in the second beat of postrest recovery in myocytes from endotoxin-treated rabbits than in normal myocytes. This was partly due to a 12% decrement in action potential duration with rest decay, which did not occur in normal myocytes. The SR Ca2+ content assessed by contractures in 10 mM caffeine was similar in the two groups. We conclude that endotoxic shock produces a LV depression in vivo that persists in isolated myocytes studied in vitro. This intrinsic myocardial depression is largely related to endotoxin-mediated sarcolemmal alterations, which shorten action potential duration, and is not due to alterations in SR function.
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PMID:Cellular mechanisms of endotoxin-induced myocardial depression in rabbits. 850 24

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

Peroxynitrite is a reactive oxidant produced from nitric oxide (NO) and superoxide, which reacts with proteins, lipids, and DNA under conditions of inflammation and shock. Here we overview the role of peroxynitrite in circulatory shock and inflammation. Immunohistochemical and biochemical evidence demonstrate production of peroxynitrite in endotoxic and hemorrhagic shock, chronic bowel inflammation, and in various forms of ischemia-reperfusion injury. The reactivity and decomposition of peroxynitrite is determined by the chemical environment, and the ratio of superoxide versus NO. Peroxynitrite can initiate toxic oxidative reactions in vitro and in vivo. Initiation of lipid peroxidation, direct inhibition of mitochondrial respiratory chain enzymes, inactivation of glyceraldehyde-3-phosphate dehydrogenase, inhibition of membrane Na+/K+ ATP-ase activity, inactivation of membrane sodium channels, and other oxidative protein modifications contribute to the cytotoxic effect of peroxynitrite. In addition, peroxynitrite is a potent trigger of DNA strand breakage, with subsequent activation of the nuclear enzyme poly-ADP ribosyl synthetase, with eventual severe energy depletion of the cells. Pharmacological evidence suggests that the peroxynitrite-poly-ADP ribosyl synthetase pathway importantly contributes to the cellular injury in endotoxic shock, inflammatory pancreatic islet cell destruction, and central nervous system ischemia. The proposal that peroxynitrite is a major cytotoxic mediator would change the interpretation of previous data on the effects of NO donors, NO synthase inhibitors, and superoxide neutralizing strategies in shock and inflammation.
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PMID:The pathophysiological role of peroxynitrite in shock, inflammation, and ischemia-reperfusion injury. 885 40

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

We examined whether tumor necrosis factor-alpha (TNF) affects the cytotoxic capacity of reactive oxygen species on rat hepatocytes in culture. Both TNF and reactive oxygen species are involved in many inflammatory events including hepatic ischemia/reperfusion injury and endotoxic shock. Synchronous treatment of hepatocytes with both TNF and H2O2 demonstrated that TNF (2000 ng/ml) enhanced the cytotoxic effect of H2O2 (500 microM). By contrast, pretreatment with TNF (2000 ng/ml) for 24 h followed by exposure to H2O2 (1000 microM) reduced the reactive oxygen-induced cytotoxicity. We conclude that TNF increases the effects of reactive oxygen-induced cytotoxicity when exposed synchronously, whereas TNF pretreatment induces a cytoprotective effect to reactive oxygen species, presumably by up-regulation of the reduced form of glutathione levels in hepatocytes.
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PMID:Tumor necrosis factor alpha alters the cytotoxic effect of hydrogen peroxide in cultured hepatocytes. 902 25

Heme oxygenase the rate-limiting step in the degradation of heme to bilirubin, generates carbon monoxide. This gaseous molecule plays important roles in neuronal signaling and modulation of vascular tone. Additionally, carbon monoxide is involved in some pathological conditions (e.g., ischemia, endotoxic shock, excitotoxicity) as a protective or toxic factor. Bilirubin, another heme metabolite, exhibits intriguing biological activities as an antioxidant, an antimutagen, and an anti-complement agent. Vital functions and the dual nature displayed by these two heme metabolites are discussed.
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PMID:New physiological importance of two classic residual products: carbon monoxide and bilirubin. 925 78

The intestine plays a major role in the pathophysiology of multiorgan failure. Although the systemic inflammatory response might be induced by endotoxin released through bacterial translocation, other factors such as intestinal ischemia might be implicated. We investigated the relationship between intestinal ischemia-reperfusion and cytokine release in rat models of hemorrhagic or endotoxic shock. Plasma levels of tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), lactate, and endotoxin, as well as macrophage TNF-alpha and IL-6 mRNA expression, were assessed at the end of shock and resuscitation. Hemodynamic changes and lactate levels suggested the presence of intestinal ischemia in both models. Mesenteric levels of TNF-alpha and IL-6 were increased by hemorrhage and further increased after saline resuscitation. Similar results were obtained with mRNA cytokine gene expression in macrophages. Endotoxin was not detectable in the hemorrhagic group. Endotoxic shock also increased production of cytokines, which, in contrast to hemorrhage, was not further increased by resuscitation. These results suggest that intestinal ischemia-reperfusion upon hemorrhage and resuscitation may be a major trigger for cytokine gene expression in the absence of endotoxin.
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PMID:Gut ischemia and mesenteric synthesis of inflammatory cytokines after hemorrhagic or endotoxic shock. 927 9

Dexanabinol, HU-211, a synthetic cannabinoid devoid of psychotropic effects, improves neurological outcome in models of brain trauma, ischemia and meningitis. Recently, HU-211 was found to inhibit brain tumor necrosis factor (TNFalpha) production after head injury. In the present study, we demonstrate the ability of HU-211 to suppress TNFalpha production and to rescue mice and rats from endotoxic shock after LPS (Escherichia coli 055:B5) inoculation. In BALB/c mice, a dose of 10 mg/kg LPS, injected i.p., caused 57% and 100% mortality, at 24 and 48 hr, respectively. HU-211, administered i.p. 30 min before lipopolysaccharide (LPS), reduced lethality to 9 and 67% at these time points (P < .05). When coinjected with D-galactoseamine (i.p.), LPS was 100% lethal within 24 hr, whereas eight hourly injections of HU-211 caused mortality of C57BL/6 mice to drop to 10% (P < .001). Administration of LPS to Sprague-Dawley rats resulted in a 30% reduction in the mean arterial blood pressure within 30 min, which persisted for 3 hr. HU-211, given 2 to 3 min before LPS, completely abolished the typical hypotensive response. Furthermore, the drug also markedly suppressed in vitro TNFalpha production and nitric oxide generation (by >90%) by both murine peritoneal macrophages and rat alveolar macrophage cell line exposed to LPS. HU-211 may, therefore, have therapeutic implications in the treatment of TNFalpha-mediated pathologies.
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PMID:Protection against septic shock and suppression of tumor necrosis factor alpha and nitric oxide production by dexanabinol (HU-211), a nonpsychotropic cannabinoid. 935 14

Oxygen metabolites formed during reperfusion of ischemic kidneys prevent recovery of renal function after short periods of renal ischemia. The administration of ATP-MgCl2 is beneficial to the survival of animals after hemorrhagic shock, severe burns, septicemia-peritonitis, post-ischemic hepatic failure, bowel ischemia, and endotoxic shock. In this study, the effect of ATP-MgCl2 on lipid peroxidation and its curative effect were evaluated by measuring the decomposition products of lipid peroxidation, detected as thiobarbituric-acid reactive substances in homogenized kidney tissues in ischemic and reperfused rabbit kidneys. Ischemia was performed by clamping the right renal artery for 60 minutes followed by 30 minutes of reperfusion. Thirty-six rabbits were classified into 6 groups containing 6 rabbits in each. In the first group, no renal ischemia-reperfusion (I-R) was designed (Sham group), the right kidney was removed 90 minutes later. In the second group, I-R was established but nothing given. Saline 0.25 cc/kg was given into the right renal artery in group 3 two minutes before ischemia, and in group 4 two minutes before reperfusion. ATP-MgCl2 17.5 mumol/kg (0.25 cc/kg) was given two minutes before ischemia in group 5, and before reperfusion in group 6. The right kidneys of the rabbits were removed and thiobarbituric-acid reactive substances in the homogenates were measured. In addition, histopathological evaluation was performed. High lipid peroxidation products were recorded in groups 2-5, whereas in group 6, these levels were low similar to those obtained in Sham group (76.72 +/- 1.01 nmol/g tissue). On histopathological evaluation, a considerable cell damage resulting from I-R trauma especially in proximal tubules was observed. In groups which were under saline effect, no histopathological damage was found. Histophatological preservation was better in group 6 rather than in group 5. The results of this study indicate that ATP-MgCl2 is remarkably effective for preventing the lipid peroxidation if given before reperfusion but not before ischemia in experimental I-R injury in rabbit kidneys.
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PMID:The effect of ATP-MgCl2 on lipid peroxidation in ischemic and reperfused rabbit kidney. 1020 3


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