Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0151744 (myocardial ischemia)
 31,282 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this work was to investigate the influence of endothelin on myocardial ischemia and reperfusion in anaesthetized dogs. Animals were submitted to left thoracotomy and 120 min of left anterior descending coronary occlusion, followed by 180 min of reperfusion. Arterial blood pressure and electrocardiogram (ECG) were recorded in order to analyze heart rate (HR)-pressure product and production of ectopic beats. Infarcted areas were identified by a macroscopic staining method and infarct size was expressed as percentage of risk zone. To inhibit the effects of endothelin in a group of animals, we administered intravenously an endothelin synthesis inhibitor (phosphoramidon) and in another group, an endothelin-1 A receptor blocker (BQ-123). Phosphoramidon decreased the HR-pressure product during reperfusion period, and both, phosphoramidon and BQ-123 decreased infarct size by 40% and the number of ventricular ectopic beats by 88% and 68%, respectively, as compared to the saline treated dogs. In conclusion, endothelin seems to play a deleterious role on the myocardium submitted to ischemia and reperfusion.
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PMID:Intravenous BQ-123 and phosphoramidon reduce ventricular ectopic beats and myocardial infarct size in dogs submitted to coronary occlusion and reperfusion. 1174 36

Endothelin-1 and norepinephrine are involved in myocardial ischemia/reperfusion injury. The aim of this study was to investigate the role of endogenously generated endothelin-1 in ischemia/reperfusion-induced norepinephrine overflow and cardiac dysfunction using a nonselective prototype of endothelin-converting enzyme (ECE) inhibitor, phosphoramidon, and a selective ECE inhibitor, SM-19712 (4-chloro-N-[[(4-cyano-3-methyl-1-phenyl-1H-pyrazol-5-yl)amino]carbonyl]benzenesulfonamide, monosodium salt). According to the Langendorff technique, isolated Sprague-Dawley rat hearts were subjected to 40-min global ischemia followed by 30-min reperfusion. Phosphoramidon and SM-19712 were perfused 30 min before ischemia and during reperfusion. Endothelin-1 level in left ventricle was increased by ischemia/reperfusion. This increase in left ventricular endothelin-1 level was suppressed by treatment with SM-19712. SM-19712 significantly improved ischemia/reperfusion-induced cardiac dysfunction such as decreased left ventricular developed pressure and dP/dt(max) and increased left ventricular end diastolic pressure. In addition, this agent suppressed excessive norepinephrine overflow in the coronary effluent from the post-ischemic heart. In contrast, treatment with phosphoramidon further enhanced left ventricular endothelin-1 level and norepinephrine overflow, and significantly worsened cardiac dysfunction after ischemia/reperfusion. These responses such as exaggerated norepinephrine overflow and the cardiac dysfunction observed after ischemia/reperfusion were markedly suppressed in the presence of a selective endothelin ET(A) receptor antagonist, ABT-627 [2R-(4-methoxyphenyl)-4S-(1,3-benzodioxol-5-yl)-1-(N,N-di(n-butyl)aminocarbonyl-methyl)-pyrrolidine-3R-carboxylic acid]. These findings indicate that cardiac endothelin-1 production is enhanced by ischemia/reperfusion, and this endogenously increased endothelin-1 is involved in post-ischemic norepinephrine overflow and cardiac dysfunction via the activation of endothelin ET(A) receptors.
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PMID:Role of endogenous endothelin-1 in post-ischemic cardiac dysfunction and norepinephrine overflow in rat hearts. 1858 23