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

A 15-year experience with 92 subcutaneous arterial bypass grafts for lower extremity revascularization has been reviewed. Fifty-nine AF and 33 FF bypass operations were performed on 89 patients whose average age was 66 years. The overall five-year survival was 33% compared to an expected survival of 80%. 88% of the AF, and 76% of the FF operations were performed for limb salvage, bypass of an aortic aneurysm, or replacement of an infected aortic graft. The remainder were performed for intermittent claudication on patients who were too ill to withstand an intra-abdominal operation. 75% of the patients with AF grafts and 64% of those with FF grafts experienced complete relief of lower extremity ischemia, including all of the patients with claudication. Graft patency was analyzed by the life table method. In the FF series, 74% of the grafts remained patent for one year; 73% for two years; 66% for three years; and 53% for four years. A 50% incidence of thrombosis occurred at the end of two years in the AF group. The patency rate of the AF grafts was also studied with regard to the type of graft material employed: a 50% incidence of thrombosis was reached at 36 months with knitted Dacron; at 18 months with weave-knit Dacron; and at 9 months with woven Dacron. THESE DATA INDICATE THAT: (1) contrary to our previous report, weave-grafts provide adequate blood flow to the lower extremities but do not remain patent as long as more conventional types of reconstruction; (2) subcutaneous grafts should be performed only when an intra-abdominal procedure is contraindicated or life expectancy is limited.
 ...
PMID:Fifteen year experience with subcutaneous bypass grafts for lower extremity ischemia. 88 58

Dietary sulfur amino acid content is a major determinant of glutathione concentration in some tissues. We examined whether brain glutathione (GSH), a key component of antioxidant defense important for minimizing ischemic injury, was also responsive to short-term sulfur amino acid deficiency. Female Long-Evans adult rats were fed a sulfur-deficient L-amino acid defined diet for five days; the control diet was supplemented with L-cystine and L-methionine (n = 6). Sulfur amino acid deficiency was confirmed by a reduction in liver cysteine and GSH concentrations, marked decreases in food intake, and weight loss. GSH concentration analyzed by reverse-phase high performance liquid chromatography was significantly depressed in the neocortex and thalamus of deficient rats. Brain cysteine was not decreased in a parallel manner. Classical glutathione peroxidase activity was increased in the liver and brain of sulfur amino acid deficient rats. This suggests an upregulation of antioxidant defense but these findings may be complicated by alterations in tissue composition. The depletion of brain GSH by a reduced supply of dietary precursors may be important during brain ischemia when the rate of GSH utilization and the need for synthesis are increased.
 ...
PMID:Sulfur amino acid deficiency depresses brain glutathione concentration. 1184 90

Hydrogen sulfide (H2S) is a gaseous mediator, produced by the metabolic pathways that regulate tissue concentrations of sulfur-containing amino acids. Recent studies indicate that endogenous or exogenous H2S exerts physiological effects in the cardiovascular system of vertebrates, possibly through modulation of K ATP channel opening. The present study was undertaken to examine the hypothesis that H2S is cytoprotective against myocardial ischemia-reperfusion injury and that this protective action is mediated by K ATP opening. Rat isolated hearts were Langendorff-perfused and underwent 30 min left main coronary artery occlusion and 120 min reperfusion. The resulting injury was assessed as infarct size, determined by tetrazolium staining. Treatment of hearts with the H2S-donor, NaHS, commencing 10 min prior to the onset of coronary occlusion and maintained until 10 min reperfusion, resulted in a concentration-dependent limitation of infarct size (control, 41.0 +/- 2.6% of risk zone; NaHS 0.1 microM, 33.9 +/- 2.1%, [0.05 > P < 0.1]; NaHS 1 microM, 20.2 +/- 2.1% [P < 0.01]). Pretreatment with the K ATP channel blockers glibenclamide 10 microM or sodium 5-hydroxydecanoate (5HD) 100 microM led to abrogation of the infarct-limiting effect of NaHS 1 microM (glibenclamide + NaHS 42.5 +/- 3.6%; 5HD + NaHS 44.7 +/- 2.2%). No statistically significant effects of NaHS treatment on coronary flow, heart rate or left ventricular developed pressure were observed in this experimental preparation. These data provide the first evidence that exogenous H2S protects against irreversible ischemia-reperfusion injury in myocardium and support the involvement of K ATP opening in the mechanism of action. Further work is required to elucidate the potential role of endogenous H2S as a cytoprotective mediator against myocardial ischemia-reperfusion injury, the mechanisms regulating its generation, and the nature of its interaction with protein targets such as the K ATP channel.
 ...
PMID:Exogenous hydrogen sulfide (H2S) protects against regional myocardial ischemia-reperfusion injury--Evidence for a role of K ATP channels. 1632 6

Cysteine is known to cause neuronal cell death and has been reported to be elevated in brain ischemia, but it has not been studied in clinical stroke. In this study, we correlated plasma levels of cyst(e)ine with long-term clinical outcome at 3 months in acute stroke. Patients were classified into 3 groups at 3 months as follows: good outcome (Rankin 0-1, n = 11), poor outcome (Rankin 2-5, n = 20), and dead (n = 5). Their plasma cyst(e)ine levels within 24 hours of stroke onset were 61 +/- 12, 67 +/- 9, and 82 +/- 14 micromol/L (standard deviation), respectively. The correlation between early plasma cyst(e)ine levels and long-term clinical outcome assessed at 3 months is significant with p < 0.001. None of the other 4 amino acids studied showed any significant correlation. Cyst(e)ine was also significantly elevated in patients who had early stroke deterioration (p < 0.02). Dose-dependent administration of cysteine increased the infarct volume by approximately 30% in a rat stroke model. This effect of cysteine was abolished by aminooxyacetic acid, an inhibitor of the enzyme cystathionine beta-synthase that converts cysteine to hydrogen sulfide (H2S), indicating that this novel neuromodulator may be acting as a mediator of ischemic brain damage. Raised plasma cyst(e)ine in patients with stroke may reflect increased production of H2S in the brain and thus predispose to poor outcome in clinical stroke. Inhibition of H2S formation may therefore be a novel approach in acute stroke therapy.
 ...
PMID:High plasma cyst(e)ine level may indicate poor clinical outcome in patients with acute stroke: possible involvement of hydrogen sulfide. 1646 2

During cardiac ischemia/reperfusion, proteins are targets of reactive oxygen species produced by the mitochondrial respiratory chain resulting in the accumulation of oxidatively modified protein. Sulfur-containing amino acids are among the most sensitive to oxidation. Certain cysteine and methionine oxidation products can be reversed back to their reduced form within proteins by specific repair enzymes. Oxidation of methionine in protein produces methionine-S-sulfoxide and methionine-R-sulfoxide that can be catalytically reduced by two stereospecific enzymes, methionine sulfoxide reductases A and B, respectively. Due to the importance of the methionine sulfoxide reductase system in the maintenance of protein structure and function during conditions of oxidative stress, the fate of this system during ischemia/reperfusion was investigated. Mitochondrial and cytosolic methionine sulfoxide reductase activities are decreased during ischemia and at early times of reperfusion, respectively. Partial recovery of enzyme activity was observed upon extended periods of reperfusion. Evidence indicates that loss in activity is not due to a decrease in the level of MsrA but may involve structural modification of the enzyme.
 ...
PMID:Alterations in mitochondrial and cytosolic methionine sulfoxide reductase activity during cardiac ischemia and reperfusion. 1667 89

The present study was undertaken to investigate the protective effect of H2S against myocardial ischemia-reperfusion (I/R) injury and its possible mechanism by using isolated heart perfusion and patch clamp recordings. Rat isolated hearts were Langendorff-perfused and subjected to a 30-minute ischemia insult followed by a 30-minute reperfusion. The heart function was assessed by measuring the LVDP, +/-dP/dt max, and the arrhythmia score. The results showed that the treatment of hearts with a H2S donor (40 micromol/L NaHS) during reperfusion resulted in significant improvement in heart function compared with the I/R group (LVDP recovered to 85.0% +/- 6.4% vs. 35.0% +/- 6.1%, +dP/dt max recovered to 80.9% +/- 4.2% vs. 43.0% +/- 6.4%, and -dP/dt max recovered to 87.4% +/- 7.3% vs. 53.8% +/- 4.9%; p < 0.01). The arrhythmia scores also improved in the NaHS group compared with the I/R group (1.5 +/- 0.2 vs. 4.0 +/- 0.4, respectively; p < 0.001). The cardioprotective effect of NaHS during reperfusion could be blocked by an ATP-sensitive potassium channel (K ATP) blocker (10 micromol/L glibenclamide). In single cardiac myocytes, NaHS increased the open probability of K ATP channels from 0.07 +/- 0.03 to 0.15 +/- 0.08 after application of 40 mumol/L NaHS and from 0.07 +/- 0.03 to 0.36 +/- 0.15 after application of 100 mumol/L NaHS. These findings provide the first evidence that H2S increases the open probability of K ATP in cardiac myocytes, which may be responsible for cardioprotection against I/R injury during reperfusion.
 ...
PMID:Hydrogen sulfide contributes to cardioprotection during ischemia-reperfusion injury by opening K ATP channels. 1806 26

Beta-adrenoceptor is over-stimulated during myocardial ischemia, in which hydrogen sulphide (H2S) concentration was found to be lowered. The present study attempted to investigate if H2S modulates beta-adrenoceptor function and the underlying mechanism. We examined the effect of NaHS (a H2S donor) on myocyte contraction and electrically-induced (EI) intracellular calcium ([Ca2+](i)) transients upon beta-adrenergic stimulation in rat ventricular myocytes with a video edge tracker method and a spectrofluorometric method using fura-2/AM as a calcium indicator, respectively. We found that isoproterenol (ISO, 10(-9)-10(-6) M), a beta-adrenoceptor agonist, concentration-dependently increased the twitch amplitude of ventricular myocytes, which was attenuated by NaHS (10(-5)-10(-3) M) in a dose-dependent manner. The amplitudes and maximal velocities (+/-dl/dt) of myocyte twitch and EI-[Ca2+](i) transient amplitudes were enhanced by ISO, forskolin (an adenylyl cyclase activator), 8-bromoadenosine-3',5'-cyclic monophosphate (an activator of protein kinase A) and Bay K-8644 (a selective L-type Ca2+ channel agonist). Administration of NaHS (100 microM) only significantly attenuated the effects of ISO and forskolin. Moreover, NaHS reversed ISO-induced cAMP elevation and forskolin-stimulated adenylyl cyclase activity. In addition, stimulation of beta-adrenoceptor by ISO significantly decreased endogenous H2S production in rat ventricular myocytes. In conclusion, H2S may negatively modulate beta-adrenoceptor function via inhibiting adenylyl cyclase activity. Impairment of this negative modulation during ischemia may induce cardiac arrhythmias. Our study may provide a novel mechanism for ischemia-induced cardiac injury.
 ...
PMID:Negative regulation of beta-adrenergic function by hydrogen sulphide in the rat hearts. 1832 40

Hydrogen sul fi de (H2S) is an endogenous gaseous mediator, produced by cystanthionine-gamma-lysase (CSE) in the cardiovascular system. Hydrogen sulfide given before ischemia can decrease myocardial ischemia and reperfusion injury. The present study investigated: (1) if hydrogen sulfide given at early reperfusion could decrease myocardial ischemia and reperfusion injury; (2) if the protective effects of hydrogen sulfide were related to mitochondrial ATP-sensitive K+ (KATP) channels opening. In isolated rat heart model, treatment of heart with NaHS (H2S donor) at the onset of reperfusion resulted in a concentration-dependent limitation of infarct size and creatine kinase release. The optimal NaHS concentration for cardioprotection is 1 microM. The cardioprotective effects of NaHS (1, 10 microM) were comparable to those of ischemic postconditioning. The KATP channels blocker, Glibenclamide or 5-hydroxydecanoate, reversed the cardioprotective effects of NaHS. The datum provided further evidence that exogenous H2S postconditioning protected rat heart against ischemia and reperfusion injury. Mitochondrial KATP channel opening is implicated in the postconditioning of H2S.
 ...
PMID:Exogenous hydrogen sulfide postconditioning protects isolated rat hearts against ischemia-reperfusion injury. 1846 95

Hydrogen sulfide (H2S) is a novel gaseous mediator produced by cystathionine-beta-synthase and cystathionine-gamma-lyase in the cardiovascular system, including the heart. Using a rat model of regional myocardial ischemia/reperfusion, we investigated the effects of an H2S donor (sodium hydrogen sulfide [NaHS]) on the infarct size and apoptosis caused by ischemia (25 min) and reperfusion (2 h). Furthermore, we investigated the potential mechanism(s) of the cardioprotective effect(s) afforded by NaHS. Specifically, we demonstrate that NaHS (1) attenuates the increase in caspase 9 activity observed in cardiac myocytes isolated from the area at risk (AAR) of hearts subjected in vivo to regional myocardial I/R and (2) ameliorates the decrease in expression of Bcl-2 within the AAR obtained from rat hearts subjected to regional myocardial I/R. The cardioprotective effects of NaHS were abolished by 5-hydroxydeconoate, a putative mitochondrial adenosine triphosphate-sensitive potassium channel blocker. Furthermore, NaHS attenuated the increase in the I/R-induced (1) phosphorylation of p38 mitogen-activated protein kinase and Jun N-terminal kinase, (2) translocation from the cytosol to the nucleus of the p65 subunit of nuclear factor-kappaB, (3) intercellular adhesion molecule 1 expression, (4) polymorphonuclear leukocyte accumulation, (5) myeloperoxidase activity, (6) malondialdehyde levels, and (7) nitrotyrosine staining determined in the AAR obtained from rat hearts subjected to regional myocardial I/R. In conclusion, we demonstrate that the cardioprotective effect of NaHS is secondary to a combination of antiapoptotic and anti-inflammatory effects. The antiapoptotic effect of NaHS may be in part due to the opening of the putative mitochondrial adenosine triphosphate-sensitive potassium channels.
 ...
PMID:Anti-apoptotic and anti-inflammatory effects of hydrogen sulfide in a rat model of regional myocardial I/R. 1863 44

The present study aimed to investigate the role of hydrogen sulphide (H2S) in the cardioprotection induced by ischemic postconditioning and to examine the underlying mechanisms. Cardiodynamics and myocardial infarction were measured in isolated rat hearts. Postconditioning with six episodes of 10-s ischemia (IPostC) significantly improved cardiodynamic function, which was attenuated by the blockade of endogenous H2S production with d-l-propargylglycine. Moreover, IPostC significantly stimulated H2S synthesis enzyme activity during the early period of reperfusion. However, d-l-propargylglycine only attenuated the IPostC-induced activation of PKC-alpha and PKC-epsilon but not that of PKC-delta, Akt, and endothelial nitric oxide synthase (eNOS). These data suggest that endogenous H2S contributes partially to the cardioprotection of IPostC via stimulating PKC-alpha and PKC-epsilon. Postconditioning with six episodes of a 10-s infusion of NaHS (SPostC) or 2 min continuous NaHS infusion (SPostC2) stimulated activities of Akt and PKC, improved the cardiodynamic performances, and reduced myocardial infarct size. The blockade of Akt with LY-294002 (15 microM) or PKC with chelerythrine (10 microM) abolished the cardioprotection induced by H2S postconditioning. SPostC2, but not SPostC, also additionally stimulated eNOS. We conclude that endogenous H2S contributes to IPostC-induced cardioprotection. H2S postconditioning confers the protective effects against ischemia-reperfusion injury through the activation of Akt, PKC, and eNOS pathways.
 ...
PMID:Endogenous hydrogen sulphide mediates the cardioprotection induced by ischemic postconditioning. 1866 Apr 50


1 2 3 4 5 6 7 8 9 Next >>