ANTIISCHEMIC EFFECTS OF NIFEDIPINE IN ISOLATED WORKING HEART PREPARATIONS OF HEALTHY, DIABETIC, AND HYPERTENSIVE RATS

We evaluated the antiischemic effects of nifedipine in isolated workin g rat hearts from age-matched normotensive Wistar-Kyoto rats (WKY), di abetic WKY, spontaneously hypertensive rats (SHR), and diabetic SHR. D iabetes was induced by streptozotocin. First, we constructed concentra tion-response curves for the negative inotropic effect of nifedipine i n every group. After 15 min of pretreatment with nifedipine (EC(60)), low-flow ischemia (30 min) was induced by reducing the afterload from 51.5 to 11.0 mm Hg and nifedipine was infused simultaneously. The six measured parameters were left ventricular pressure (LVP), maximum rate of pressure increase (+dP/dt(max)), maximum rate of pressure decrease (-dP/dt(max)), aortic output (AO), coronary flow (CF), and cardiac ou tput (CO), determined after 15-min equilibration in the working heart mode and at the end of the experiment. From these data, the recovery p ercentages were calculated. There were no significant differences in s ensitivity to nifedipine (as measured by the EC(50) concentration) bet ween the four groups with respect to LVP, +dP/dt(max), -dP/dt(max), CF , and CO. However, hearts from SHR were less sensitive to nifedipine t han those from diabetic SHR and nondiabetic WKY with regard to AO. In isolated hearts from nondiabetic WKY and SHR, there were no significan t differences between vehicle-treated organs and nifedipine-treated pr eparations. In hearts from diabetic WKY and diabetic SHR, however, the nifedipine-treated group (LVP 87.1 +/- 3.3 and 60.5 +/- 12.1%, respec tively) recovered significantly (p < 0.05) better from ischemia as com pared with the control group (LVP 35.7 +/- 14.7 and 10.7 +/- 9.8%, res pectively) (n = 6 for each group). Hearts from diabetic rats treated w ith nifedipine recovered much better from ischemia than did hearts der ived from nondiabetic rats.