The Effect of Chronic Co-Administration of Morphine and Verapamil on Isoproterenol-Induced Heart Injury

Objective: Long-term co-administration of morphine and calcium channel antagonists (CCAs) is likely in some clinical conditions. Reciprocal interactions during chronic concomitant use of these agents are confirmed in central nervous system studies. However, there is little information regarding their chronic combination effects on the cardiovascular system. Present study was designed to assess the effects of chronic co-administration of morphine plus verapamil on some cardiovascular indices of rats with / without myocardial damage. Methods: Animals were divided to control, morphine, verapamil and morphine plus verapamil groups each consisted of two subgroups, with and without heart injury. Rats were treated with increasing doses of morphine (10-20mg/kg, i.p.) or morphine plus verapamil (10mg/kg, i.p.) daily for 7 days. Heart injury was induced by isoproterenol (50 mg/kg, i.p.), then cardiac Troponin I was measured and on day 8, blood pressure and heart rate was recorded and then the hearts were histopathologically examined. Results: The results indicated that co-administration of morphine with verapamil has stronger cardioprotective effect than morphine or verapamil alone as confirmed by the lower Troponin I level and myocardial lesion grades. However, no additional effects on mean arterial pressure and Rate-Pressure product were observed in combined use of these drugs. Conclusion: These findings suggest chronic co-administration of morphine and verapamil induced additive protective effects on rat heart exposed to myocardial injury comparing with each of them alone.