Cardioprotective actions of nisoldipine in postreperfusion myocardial ischemia.
Nisoldipine, a dihydropyridine with calcium channel-blocking activity, was studied in myocardial ischemia and reperfusion in cats. At an infusion rate of 3 micrograms/kg/hr, nisoldipine did not significantly alter the product of mean arterial blood pressure and heart rate, the pressure-rate index. When infusion of nisoldipine was started 30 minutes after occlusion and continued for 5 1/2 hours, nisoldipine exerted a marked antiischemic effect. This effect was manifested as a significant reduction in necrotic myocardial tissue expressed either as a percentage of area at risk (p less than 0.01) or as a percentage of total left ventricle (p less than 0.01). The washout of creatine kinase into the circulation was also reduced in nisoldipine-treated cats. When nisoldipine infusion started at 60 minutes after ischemia, the effects were still significant (p less than 0.05) but less striking, and when nisoldipine infusion was delayed until 90 minutes after ischemia, no significant cardioprotection was observed. Nisoldipine also blunted the washout of creatine kinase into the peripheral circulation on reperfusion. Thus nisoldipine exerts a cardioprotective effect in cats during myocardial ischemia independent of reducing myocardial oxygen demand. The effect is optimal when nisoldipine is given during the first 30 minutes of ischemia and declines thereafter, reaching insignificant effects at 90 minutes.
Mentley
R K
RK
Department of Physiology, Jefferson Medical College, Thomas Jefferson University, Philadelphia, PA 19107.
Brezinski
M E
ME
Tse
E
E
Lefer
A M
AM
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002121:Calcium Channel Blockers / Q000627:therapeutic use*; D002415:Cats; D003326:Coronary Circulation; D003327:Coronary Disease / Q000188:drug therapy*; D003402:Creatine Kinase / Q000097:blood; D004562:Electrocardiography; D006339:Heart Rate / Q000187:drug effects; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009543:Nifedipine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D015737:Nisoldipine; D010101:Oxygen Consumption / Q000187:drug effects; D010477:Perfusion; D013997:Time Factors
D002121:Calcium Channel Blockers; D015737:Nisoldipine; D003402:Creatine Kinase; D009543:Nifedipine