Journal of cardiovascular pharmacology
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J. Cardiovasc. Pharmacol. · Jun 1994
Comparative StudyProtection of reperfused ischemic pig myocardium by nexopamil, a new combined Ca2+ and serotonin antagonist.
We investigated the ability of a newly developed calcium and serotonin (5-HT2) antagonist, nexopamil, to protect the heart from ischemia- and reperfusion-induced myocardial injury. Anesthetized open-chest minipigs were subjected to 1 h left anterior descending coronary artery (LAD) occlusion and 3-h reperfusion. Thirty minutes before occlusion, one group of pigs (n = 7) received nexopamil (0.1 mg/kg intravenously, i.v.) and another group (n = 9) received vehicle. ⋯ Nexopamil significantly increased the transcardiac (coronary venous-arterial) concentration gradients of 6-oxo-prostaglandin F1 alpha (PGF1 alpha) without changing thromboxane (B2 (TBX2) concentrations, indicating a selective increase in cardiocoronary PGI2 formation. Nexopamil reduces myocardial injury in reperfused ischemic myocardium. Besides calcium channel blocking activity, inhibition of ischemia-induced neutrophil activation and enhanced endogenous PGI2 formation may be factors contributing to the beneficial effects of nexopamil.