Noguchi K, Kato T, Kinjo N, Moromizato H, Sakanashi M
Department of Pharmacology, School of Medicine, Faculty of Medicine, University of the Ryukyus, Okinawa, Japan.
Jpn J Pharmacol. 1990 Jul;53(3):381-91. doi: 10.1254/jjp.53.381.
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 greater than 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.
研究了阿罗洛尔(一种α和β肾上腺素受体联合阻断剂)对麻醉犬严重冠状动脉狭窄所致局部心肌功能障碍的影响,并与拉贝洛尔和普萘洛尔进行了比较。选择这三种拮抗剂的剂量以产生相当程度的负性变时和变力作用,但α肾上腺素受体阻断效能不同(拉贝洛尔大于阿罗洛尔)。通过结扎左旋冠状动脉(LCX)将局部心肌功能(以节段缩短率(%SS)衡量)降低至约2 - 3%,然后静脉注射药物或生理盐水。给药30分钟后解除LCX结扎。静脉注射生理盐水后至少30分钟内,与给药前值相比,血流动力学和收缩性参数未见明显改变。阿罗洛尔和普萘洛尔均降低心率和左心室最大正压变化速率(LVdP/dt),而LCX血流量无明显变化。同时,阿罗洛尔和普萘洛尔显著改善冠状动脉狭窄远端的%SS。另一方面,拉贝洛尔可能由于系统性低血压而显著降低LCX血流量,尽管该药物显著降低心率和LVdP/dt,但未能改善缺血区域的%SS。这些结果表明,阿罗洛尔与普萘洛尔以相似的方式改善冠状动脉狭窄远端受损的局部心肌功能。