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)

Ischemia (4-hour) followed by reperfusion (4-hour) of rat hind limbs results in local injury as well as remote (lung) injury. It has recently been shown that injury in this model is neutrophil- and cytokine-dependent and requires the beta 2 integrin adhesion molecules CD11a/CD18 and CD11b/CD18. The role of selectins in events leading to injury (as determined by leakage of albumin and by hemorrhage) was assessed either through the use of blocking antibodies to L-, E- or P-selectins or by the use of oligosaccharides that are reactive with selectins. Lung injury was found to be L- and E-selectin-dependent. When the ischemia and reperfusion times were reduced, lung injury was also found to be P-selectin dependent. In the case of hind limb injury involving the crural muscle mass, injury was L-selectin-dependent but independent of requirements for P- and E-selectin. Injury in both organs was blocked by the infusion of sialylated Lewis pentasaccharide, whereas sialyl-N-acetyllactosamine pentasaccharide failed to protect against injury. In general, when selectin-blocking approaches were protective, there were parallel reductions in tissue content of myeloperoxidase. These data underscore the role of selectins in ischemia-reperfusion injury and suggest that selectin requirements may vary with the vascular bed under study.
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PMID:Role of selectins in local and remote tissue injury following ischemia and reperfusion. 751 Apr 57

The cardioprotective effects of L-659,989, a specific platelet-activating factor (PAF) receptor antagonist, were investigated in an ischemia/reperfusion model in rats. Pentobarbital-anesthetized rats were subjected to left main coronary artery occlusion (1 h) followed by reperfusion (1 h) (MI/R); Sham-operated rats were used as controls (Sham MI/R). Rats receiving vehicle showed reduced survival rate (60%), marked myocardial injury (necrotic area/total area = 54.5 +/- 6%; necrotic area/area at risk 76.6 +/- 6.7%), high serum creatine phosphokinase (CPK) activity (150 +/- 10 U/ml), and increased myocardial myeloperoxidase (MPO) activity in the area at risk (AR, 6.2 +/- 0.5 U x 10(-3)/g protein) and in the necrotic area (6.6 +/- 0.7 U x 10(-3)/g protein). PAF plasma levels increased significantly during reperfusion and peaked at 15 min of reperfusion. Administration of L-659,989 enhanced survival rate (80%), reduced myocardial damage (necrotic area/total area 25.6 +/- 3.5%; necrotic area/AR 34.6 +/- 5.4%), attenuated the increase in serum CPK (50 +/- 6 U/ml) and decreased MPO activity both in the AR (2.8 +/- 0.3 U x 10(-3)/g tissue) and in the necrotic area (2.3 +/- 0.5 U x 10(-3)/g tissue). Our results suggest that PAF-inducing adhesion and activation of polymorphonuclear leukocytes (PMN) plays a significant role in the injury associated with ischemia/reperfusion.
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PMID:Protective effects of L-659,989, a platelet-activating factor receptor antagonist, in myocardial ischemia and reperfusion in rats. 751 38

The role of P-selectin in leukocyte-endothelial interaction after splanchnic arterial occlusion and reperfusion (SAO/R) in pentobarbital-anesthetized rats was investigated employing a P-selectin-neutralizing monoclonal antibody (i.e., MAb PB1.3). MAb PB1.3 (1 mg/kg) given intravenously to SAO/R rats just before reperfusion significantly attenuated leukocyte rolling and adherence in mesenteric postcapillary venules as observed via intravital microscopy. Likewise, ileal myeloperoxidase (MPO) activity was decreased from 4.6 +/- 0.6 in nontreated ischemic rats to 2.0 +/- 0.2 U/100 mg (P < 0.01), indicating a lesser degree of polymorphonuclear leukocyte (PMN) accumulation. A significantly lower plasma free amino-nitrogen concentration was observed in MAb PB1.3-treated rats vs. untreated (P < 0.01), suggesting decreased tissue injury after reperfusion. Immunohistochemical localization demonstrated significant expression of P-selectin in endothelial cells lining ileal postcapillary venules 30 min after reperfusion of the ischemic splanchnic circulation. Thus P-selectin appears to plays an important role in leukocyte accumulation after splanchnic ischemia-reperfusion, and the MAb PB1.3 attenuates the accumulation of PMNs in the ischemic-reperfused small bowel, resulting in reduced tissue injury.
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PMID:Role of P-selectin in microvascular leukocyte-endothelial interaction in splanchnic ischemia-reperfusion. 752 Jun 70

Nitric oxide (NO), originally identified as the mediator of endothelial-dependent relaxation of vascular smooth muscle, is now known to also have cytotoxic effects under certain conditions. Thus, we have investigated the effects of inhibition of NO synthesis on ischemia/reperfusion injury in the rabbit rectus femoris muscle. Three and a half hours of ischemia and 24 hours of reperfusion resulted in a 56% loss of viability. In muscles receiving an infusion of the nitric oxide synthase inhibitor, L-NIO (30 microM), the loss of viability was reduced to 15%. Post-ischemic blood flow was increased in muscles receiving a saline infusion, whereas there was a marked decrease in blood flow for at least the first 60 minutes of reperfusion in muscles treated with L-NIO (30 microM). The increase in myeloperoxidase levels (indicative of neutrophil accumulation) following 24 hours of reperfusion was attenuated with L-NIO infusion by approximately 50% and the reperfusion-induced edema was also attenuated in L-NIO treated muscle. These findings suggest that endogenous NO production during ischemia/reperfusion injury may be deleterious to muscle survival.
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PMID:Nitric oxide synthase inhibitor, nitro-iminoethyl-L-ornithine, reduces ischemia-reperfusion injury in rabbit skeletal muscle. 753 77

Rebamipide (2-(4-chlorobenzoylamino)-3-[2-(1H)-quinolinon-4-yl] propionic acid), a novel antiulcer agent, has been reported to prevent various acute experimental gastric mucosal lesions and to accelerate the healing of chronic gastric ulcers. We investigated the effect of rebamipide on rat gastric mucosa damaged by exposure to 30 min of ischemia and 60 min of reperfusion (I/R) with continuous intragastric instillation of 0.1 N HCl (1 ml/100 g body weight) into the stomach. Rebamipide, at 30 and 100 mg/kg, i.p., reduced the mucosal damage score from 2.28 (I/R vehicle group) to 1.54 and 1.07, respectively. Pretreatment with rebamipide significantly reduced the activity of myeloperoxidase (an index of neutrophil infiltration) and preserved the activities of superoxide dismutase and nitric oxide synthase in the gastric mucosa with inhibition of malondialdehyde production. Thus, a negative correlation between the activities of nitric oxide synthase and myeloperoxidase (y = 4.35-9.45x, r = .67, P < .01) was observed. In an in vitro study, rebamipide inhibited N-formyl-met-leu-phe-induced chemotaxis of neutrophils and production of superoxide anion from opsonized zymosan-stimulated neutrophils. However, it did not affect the production of superoxide anion either by the xanthine-xanthine oxidase reaction or phorbol 12-myristate 13-acetate-stimulated neutrophils. Based on these results, it is suggested that rebamipide exerts a protective effect on the I/R-induced gastric mucosal damage through inhibition of mobilization and activation of neutrophils in association with an attenuation of the decreases in both superoxide dismutase and nitric oxide synthase activities, thereby preventing the gastric microcirculation from deterioration.
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PMID:Preventive effect of rebamipide on gastric lesions induced by ischemia-reperfusion in the rat. 756 69

In the present study a novel nitric oxide (NO) donor, CAS-1609, was utilized as a means of coronary NO replenishment in a canine model of myocardial ischemia-reperfusion. Administration of CAS-1609 (1.25 mg iv) 10 min before reperfusion, followed by a 1 mg/h intracoronary infusion throughout the 4.5-h reperfusion period, resulted in significant improvement in postischemic transmural myocardial blood flow (0.66 +/- 0.09 vs. 0.37 +/- 0.08 ml.min-1.g-1 for saline vehicle, P < 0.05). Dogs receiving NO supplementation also exhibited a significant recovery of myocardial contractility after 4.5 h of reperfusion (30 +/- 2% area ejection fraction vs. 22 +/- 2% for saline vehicle, P < 0.05). Moreover, myocardial necrosis as a percentage of the area at risk was reduced from 28.9 +/- 4.3% in the saline group to 8.5 +/- 2.6% in the CAS-1609 group (P < 0.01), while ischemic zone myeloperoxidase activity, indicative of neutrophil infiltration, was also attenuated by 70% with NO therapy. Injection of acetylcholine and nitroglycerin into the left circumflex coronary artery revealed a significant impairment of vasodilator responses in the saline vehicle dogs at 2 h of reperfusion. However, dogs treated with the NO donor demonstrated postischemic vasodilator responses which were similar to baseline (P = not significant vs. baseline). These studies demonstrate that intracoronary administration of NO significantly augments postischemic coronary blood flow and contractile function following ischemia and reperfusion. In addition, NO therapy reduces coronary vascular injury, attenuates myocardial necrosis, and reduces neutrophil infiltration. The cardioprotective actions of intracoronary NO administration may be related to the potent antineutrophil actions of NO.
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PMID:Intracoronary nitric oxide improves postischemic coronary blood flow and myocardial contractile function. 757 9

Hearts exposed to global myocardial ischemia associated with cardiac surgery often suffer postischemic endothelial and contractile dysfunction related to antecedent regional or global ischemia. Our studies tested the hypothesis that supplementing blood cardioplegia and reperfusion with the nitric oxide (NO) precursor L-arginine or the NO donor SPM-5185 would preserve endothelial function, reduce infarct size, and reverse postcardioplegia regional contractile dysfunction or global dysfunction. In the first study involving 23 anesthetized dogs undergoing regional ischemia, supplementation of blood cardioplegia with L-arginine: (1) reduced infarct size; (2) improved postischemic regional segmental work and diastolic stiffness; (3) attenuated neutrophil accumulation in the area at risk; and (4) improved postischemic depressed coronary artery endothelial function. The NO synthase inhibitor N-nitro-L-arginine (L-NA) reversed these protective effects. In another experiment involving 18 anesthetized dogs undergoing normothermic global ischemia, hearts treated with blood cardioplegia supplemented with the NO donor SPM-5185 demonstrated better postischemic coronary artery endothelial function, lowered myeloperoxidase activity in the ischemic-reperfused myocardium, and significantly improved global ventricular function in the group receiving high-dose SPM-5185. We conclude that the inclusion of L-arginine or high-dose NO donor SPM-5185 in blood cardioplegia improves postischemic ventricular performance and endothelial function in ischemically injured hearts, possibly by inhibition of neutrophil-mediated damage via the L-arginine-NO pathway.
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PMID:Augmentation of microvascular nitric oxide improves myocardial performance following global ischemia. 757 37

A study was designed to investigate the possibility of reducing peritoneal adhesion formation in mice by pretreatment with allopurinol. Allopurinol, at a dose of 35 mg/kg of body weight/d significantly reduced the severity of peritoneal adhesions (P < .001), and also the neutrophil response to ischemia (P < .05). Tissue myeloperoxidase activity at the site of ischemic injury was significantly lower in the allopurinol-treated mice at the end of 2 weeks (P < .001). However, xanthine oxidase was undetectable in both control and allopurinol-treated mice. These observations suggest that allopurinol reduces the severity of peritoneal adhesion formation in mice, possibly by reducing the neutrophil response to ischemia.
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PMID:Allopurinol reduces the severity of peritoneal adhesions in mice. 759 27

Changes in mucosal permeability may be important in the etiology of necrotizing enterocolitis. The authors have previously shown that subclinical ischemia-reperfusion injury results in increased permeability in the rat intestine, and have partially characterized this phenomenon. In the present study the authors attempt to determine the mechanism by which these changes occur. Six-week-old rats underwent 10-minute superior mesenteric artery occlusion (SMAO) or sham, and mucosal permeability to 51CrEDTA was measured after 30 minutes. Rats were pretreated with saline, inhibitors of oxygen free radicals (superoxide dismutase+catalase, vitamin E, allopurinol, alpha-phenyl-N-tert butyl-nitrone), inhibitors of eicosanoids (indomethacin, quinacrine, diethylcarbamazine, 13-azaprostanoic acid), the putative cytoprotective agent prostaglandin E2, or the inhibitor of neutrophil free radical production fructose 1-6 diphosphate. None of the agents significantly attenuated the increase in mucosal permeability caused by SMAO, although indomethacin and prostaglandin E2 significantly exacerbated the permeability changes. To further explore the role of neutrophils, tissue myeloperoxidase was measured 30 minutes after SMAO. There was no significant difference in myeloperoxidase levels between sham and SMAO animals. These data suggest that the early increase in mucosal permeability after subclinical ischemia-reperfusion injury is not mediated by oxygen free radicals, eicosanoids, or neutrophils. The deleterious effect of indomethacin and prostaglandin E2 suggests a possible protective role for the cyclooxygenase system, but further studies are necessary to elucidate this possibility.
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PMID:Mucosal permeability after subclinical intestinal ischemia-reperfusion injury: an exploration of possible mechanisms. 759 36

Gut ischemia/reperfusion (I/R) provokes lung injury via a mechanism that involves neutrophils [polymorphonuclear neutrophils (PMNs)]. CD11b/CD18 (alpha mB2) is the integrin receptor on PMNs critical for adhesion-dependent oxidative burst. The purpose of this study was to investigate the mechanistic role of CD11b in the process of gut I/R-induced lung injury. Sprague-Dawley rats underwent 45 minutes of superior mesenteric artery (SMA) occlusion with and without CD11b monoclonal antibody treatment (IB6) (1 mg/kg, i.v.), before SMA clamping. At 2-hour reperfusion, PMN presence in tissue was quantitated by myeloperoxidase activity and circulating PMN priming determined by the difference in superoxide production with and without N-formyl-methionyl-leucyl-phenylalanine, whereas lung leak was assessed by 125I-albumin lung/blood ratio. In sum, CD11b blockade prevented gut I/R-induced lung leak, but did not attenuate gut I/R-induced PMN priming or tissue PMN accumulation. In conclusion, gut I/R promotes PMN priming and PMN adhesion in both local and distant beds via receptors other than CD11b, but this B2 integrin receptor is critical for PMN-mediated endothelial injury.
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PMID:CD11b blockade prevents lung injury despite neutrophil priming after gut ischemia/reperfusion. 763 6


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