Antiarrhythmic effect of endothelin-A receptor antagonist on acute ischemic arrhythmia in isolated rat heart

摘要

AIM: To observe the effects of endothelin receptor subtype A (ET_A ) and B (ET_B ) antagonists on acute ischemic arrhythmia in isolated rat heart, and to determine whether endogenous endothelin (ET) was implicated in the patho-physiological process of arrhythmia induced by acute myocardial ischemia. METHODS: Fifty-three SD male rats were randomized into 8 groups. Heart was isolated and perfused in Langendorff mode and acute ischemia model was established by ligation of the left anterior descending (LAD) coronary artery. The effects of ET_A receptor antagonist PD156707 and ET_B receptor antagonist IRL1038 on arrhythmia, heart function, the myocardial activity of superoxide dismutase (SOD), and the content of melondialdehyde (MDA) during the acute 60-min ischemic phase were analyzed. RESULTS: Pretreatment with PD156707 (20-500 nmol/L) dose-dependently improved the ischemic isolated heart function, enhanced SOD activity and decreased MDA content in the ischemic myocardium, and suppressed the acute ischemic arrhythmia. Conversely pretreatment with IRL1038 did not change the heart function, SOD activity, MDA content, and the acute ischemic arrhythmia significantly as compared with the occlusion control. CONCLUSION: ET_A receptor antagonist effectively improved heart function, enhanced anti-oxida-tive function of the myocardium and reduced arrhythmia during the acute ischemic phase in isolated rat hearts, while ET_B receptor antagonist did not exert protective effects, suggesting that endogenous ET-1, acting through ET_A receptor, may be one of the factors implicated in arrhythmia and impairment to heart function during the acute ischemic phase.