Participation of the vasodilating property of nipradilol in improving ischemic derangement of myocardial energy metabolism.
The effects of equipotent doses in negative inotropic and chronotropic properties of nipradilol [10 micrograms/kg/min intravenously (i.v.)] and propranolol (20 micrograms/kg/min i.v.) on hemodynamics and transmural energy metabolites in ischemic hearts were examined in anesthetized dogs. After 5-min infusion of these agents, coronary perfusion pressure of 30 mm Hg was induced by acute coronary stenosis for 10 min. Coronary blood inflow and myocardial contractile force (MCF) in the control ischemic area decreased to about one-third and two-thirds of the respective starting levels. In the nipradilol group, similar changes were observed, but in the propranolol group the MCF tended to decrease further. Cardiac effort index decreased to about two-thirds in both groups. The left ventricular end-diastolic pressure (LVEDP) increased by 4.3 mm Hg with saline, by 8.8 mm Hg with propranolol, and by 1.3 mm Hg with nipradilol. ATP depletion in the ischemic myocardium (by 29 and 22% in inner and outer layers, respectively) was restored to normal level by either agent. A decrease in creatine phosphate and an accumulation of lactate were significantly alleviated by nipradilol (by 74 and 59----by 39 and 21%, and by 4.9 and 2.3----by 0.7 and 0.2 times, respectively), but not by propranolol. The results indicate that in addition to a decrease in myocardial oxygen consumption caused by the beta-adrenoceptor blocking effects of nipradilol, reductions in preload and afterload caused by the vasodilating property significantly contribute to nipradilol-induced improvement in the ischemic derangement of transmural energy metabolism.
Higuchi
M
M
Department of Pharmacology, Saga Medical School, Japan.
D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D002302:Cardiac Output / Q000187:drug effects; D003327:Coronary Disease / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D003331:Coronary Vessels / Q000187:drug effects; D004285:Dogs; D004734:Energy Metabolism / Q000187:drug effects*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D007773:Lactates / Q000378:metabolism; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D011412:Propanolamines / Q000627:therapeutic use*; D011433:Propranolol / Q000494:pharmacology; D014665:Vasodilator Agents / Q000627:therapeutic use*
D007773:Lactates; D010710:Phosphates; D011412:Propanolamines; D014665:Vasodilator Agents; D010725:Phosphocreatine; D011433:Propranolol; C036089:nipradilol