Application Of Endothelin A-receptor Antagonist BQ123 To The Models Of Myocardial Infarction Of Rabbits

Objective: To elucidate cardioprotective effects of ETA receptor antagonist after AMI, especially effects of long-term treatment with ETA receptor antagonists on ventricular remodeling and on cardiac constrictivity post-AMI, and to learn wether the distribution of ET-1 and ET receptor(ETR) in local infarcted myocardium is diffirent after application of ET receptor antagonists. Methods: 22 rabbits were randomly divided into 4 groups: 1 week experiment group(n=6) and control group(n=5); 4 weeks expriment(n=6) and control group(n=5). The models of myocardial infarction were induced in all animals by ligating the beginning of left ventricular anterior descending coronary arteries. All the animals in expriment groups were treated with intravenous infusion of ETA receptor antagonist BQ123, and control groups were treated by the same way with equal dose of the solutions of 0.9% NaCI. The animals were killed after. 1 and 4 weeks respectively, and the hearts were removed, Infarcted size was calculated as percentage of the left ventricle, and left ventriclar mass index(LVMI) was calculated. The indices of left ventriclular structure and cardiac function were assessed by two dimension echocardiography and doppler echocardiography before ligating coronary and being killed. ET-1-like-immunoreactivity(ET-l-ir) and ETR-like-immunoreactivity(ETR-ir) in left ventricular myocardial tissues were detected by immunohistochemistry and image analysis method. Results: Infarcted sizes were significantly reduced in expriment groups compared to their control groups respectively(P<0.05). The decreased degrees of ejection fraction(EF) and left ventricular fractional shortening(LVFS) weresignificantly lower in 4 weeks experiment group compared to its control group(P<0.05). LVMK the increased degrees of interventricular depth(IVd) and left ventricular posterior wall depth(LVPWd) and expansion of left ventricular end-diastolic volume(LVEDV) in 4 weeks expriment group were significantly lower than 4 weeks control group(P<0.05). The upregulated levels of ET-1 and ETR expression in each experiment group were significantly lower than its control group respectively(P<0.05). Conclusions: Long-term treatment with TA receptor antagonist BQ123 could decrease infarcted sizes % ventricular remodeling and reduce the upregulation of ET-1 and ETR expression, and cardiac function improved significantly.