Improved Recovery of Myocardial Segment Function Following a Short Coronary Occlusion in Dogs by Nicorandil, a Potential New Antianginal Agent, and Nifedipine

Abstract

The effects of nicorandil [SG-75, 2-nicotinamidoethyl nitrate (ester)] and nifedipine on the recovery of myocardial segment shortening were compared to a vehicle-treated group following a short occlusion (15 min) of the left anterior descending coronary artery (LAD) and reperfusion (5 h). The relationship between myocardial blood flow and myocardial segment shortening was examined by means of the radioactive microsphere technique and sonomicrometry. Nicorandil (100 .mu.g/kg followed by 25 .mu.g/kg per min, i.v.) or nifedipine (3 .mu.g/kg followed by 1 .mu.g/kg per min, i.v.) was administered 10 min prior to and throughout the occlusion period. Both drugs produced similar decreases in mean arterial pressure (.apprx. 25 mm Hg) during LAD occlusion. Similar degrees of ischemia (flow deprivation) were produced in the vehicle, nicorandil, and nifedipine groups; however, nicorandil produced a significantly greater decrease in the heart rate-left ventricular systolic pressure product during coronary occlusion. During reperfusion of the LAD there was no difference in the hemodynamics of the vehicle, nicorandil or nifedipine groups. Neither drug altered myocardial blood flow to the ischemic region during the occlusion or reperfusion period when compared to the vehicle-treated group ; however, both nicorandil and nifedipine pretreatment significantly improved recovery of percentage of segment shortening of the ischemic region. Nicorandil improved the recovery of function (percentage of segment shortening) to a greater extent than did nifedipine throughout the reperfusion period, most likely because of the greater decrease in afterload produced by nicorandil. The improvement in recovery of percentage of segment shortening after administration of nicorandil as compared to nifedipine was caused by a decrease in systolic segment length, since both drugs produced similar decreases in diastolic length when compared to the vehicle group. Thus, nicorandil and nifedipine treatment during a short coronary artery occlusion improved the recovery of myocardial function following reperfusion. This improvement in function, however, did not appear to be related to changes in myocardial blood flow and may be the result of decreases in myocardial O2 demands produced by nicorandil and nifedipine during the ischemic period.