Cilnidipine, a N+L-type dihydropyridine ca channel blocker, suppresses the occurrence of ventricular premature arrythmia during ischemia and reperfusion in rabbits

Background:Ca channel blockers are widely prescribed for the treatment of hypertension and coronary artery diseases. However, it is still unknown whether dihydropyridine Ca channel blockers are protective against arrythmias. We investigated whether cilnidipine, a N+L-type Ca channel blocker reduces the incidence of ventricular premature arrythmia during ischemia and reperfusion.Methods and Results:Forty Japanese white rabbits underwent 30 min ischemia and 30 min reperfusion. Cilnidipine (0.5 or 1.0 microgram/kg/min, i.v.), nifedipine (3.0 microgram/kg/min, i.v.) or saline was continuously during ischemia and reperfusion. Electrocardiogram and blood pressure were monitored and the incidences of ventricular premature beats (VPBs) during ischemia and reperfusion were measured. In other 21 rabbits, myocardial interstitial noradrenaline levels were determined before, during and after 30 min of ischemia with cilnidipine (1.0 microgram/kg/min, n=7), nifedipine (3.0 microgram/kg/min, n=7) or saline (n=7) using a microdialysis technique. The incidences of VPBs during ischemia and during reperfusion were significantly attenuated in the cilnidipine 0.5 and 1.0 groups but not in the nifedipine group compared to the control group. Myocardial interstitial noradrenaline levels were significantly reduced in the cilnidipine 1.0 group but not in the nifedipine group compared to the control. Conclusion:Cilnidipine but not nifedipine attenuates the incidence of ventricular premature beats during ischemia and reperfusion and this effect may be related to decreased cardiac sympathetic nerve activity in rabbits.