Do all calcium antagonists have a cardioprotective effect against isoproterenol induced myocardial necrosis in rats?

ABSTRACT

This study investigated and compared the possible protective effects of five Ca2+ entry blockers Verapamil, nifedipine, diltiazem, flunarizine and amlodipine against isoproterenol-induced myocardial necrosis in rats. Fifty-six male albino rats were divided into seven equal groups. Group 1 served as control, group 2 received isoproterenol [85 mg/kg body wt. s.c.] for two days to produce myocardial necrosis, other groups received one of the following Ca2+ entry blockers for four successive days verapamil [5 mg/kg body weight i.p.], nifedipine [0.2 mg/kg i.m.], diltiazem [10 mg/kg i.m.], flunarizine [30 mg/kg orally] and amlodipine [0.5 mg/kg orally]. On the third and fourth days of treatment, animals received isoproterenol in the dose mentioned above. Twenty-four hours later, blood samples were withdrawn from the orbital plexus for the determination of creatine phosphokinase [CPK] activity, aspartate aminotransferase [ASAT] and alanine aminotransferase [ALAT]. The post-ischemic survival rate [PISR] for each group was calculated. Isoproterenol caused a significant increase in CPK, ASAT and ALAT as compared to the control group, the PISR was 0%. Pretreatment with nifedipine, verapamil or diltiazem significantly reduced all the enzyme studied as compared to isoproterenol group, the PISR was 87.5% 75% and 75%, respectively. Amlodipine pretreatment reduced only ASAT, PISR was 25%. On the other hand, flunarizine pretreatment did not significantly change the enzyme studied, the PISR was 12.5%. The results suggested that nifedipine, verapamil and diltiazem have protective effects against isoproterenol-induced myocardial necrosis in rats and that flunarizine and amlodipine were free of these cardioprotective effects