COMPARATIVE EFFECTS OF AROTINOLOL, LABETALOL AND PROPRANOLOL ON REGIONAL MYOCARDIAL DYSFUNCTION INDUCED BY FLOW-LIMITING CORONARY STENOSIS IN ANESTHETIZED DOGS

Effects of arotinolol, a combined alpha-and beta-adrenoceptor blocking agent, on regional myocardial dysfunction produced by severe coronary stenosis in anesthetized dogs were examined and compared with those of labetalol and propranolol. Doses of these three antagonists were selected to produce a comparable degree of the negative chrono-and inotropic effect but a different potency of alpha-adrenoceptor blockade (labetalol>arotinolol). Regional myocardial function measured as segment shortening (%SS) was decreased to around 2–3% by constriction of the left circumflex coronary artery (LCX), and then drug or saline was administered i.v. The stenosis of LCX was released 30 min after the administration. No significant alteration in hemodynamic and contractility parameters was seen as compared to the predrug value up to at least 30 min after saline i.v. Arotinolol and propranolol both reduced heart rate and peak positive left ventricular dP/dt (LVdP/dt) without a significant change in LCX flow. Concomitantly, %SS distal to a coronary stenosis was significantly improved by arotinolol and propranolol. On the other hand, labetalol significantly reduced LCX flow probably due to systemic hypotension and failed to improve %SS in the ischemic area, although the agent markedly decreased heart rate and LVdP/dt. These results indicate that arotinolol improves impaired regional myocardial function distal to a coronary stenosis in a similar manner with propranolol. © 1990, The Japanese Pharmacological Society. All rights reserved.