Hoque A N, Nasa Y, Abiko Y
Department of Pharmacology, Asahikawa Medical College, Japan.
Eur J Pharmacol. 1993 May 19;236(2):269-77. doi: 10.1016/0014-2999(93)90598-c.
In the isolated, perfused working rat heart, ischemia (15 min) decreased mechanical function and also the tissue levels of ATP and creatine phosphate, and increased the tissue levels of lactate and free fatty acids including arachidonic acid. Reperfusion (20 min) did not restore mechanical function, but restored changes of metabolites incompletely except for free fatty acids, which changed further during reperfusion. Drugs were given 5 min before ischemia until the end of ischemia or for the first 10 min after reperfusion. Both dl- and d-propranolol (10 and 30 microM) decreased mechanical function, accelerated the recovery of mechanical function during reperfusion following ischemia, and attenuated ischemia reperfusion-induced metabolic changes. The attenuation of reperfusion-induced metabolic changes was more marked when these drugs were present during reperfusion. d-Propranolol showed a cardioprotection similar to that by dl-propranolol. Timolol (50 microM) did not accelerate the recovery of mechanical function during reperfusion, and did not attenuate the reperfusion-induced metabolic changes. These results suggest that d-propranolol, like dl-propranolol, has a cardioprotective effect which is probably due to its membrane stabilizing (or sodium channel blocking) action.
在离体灌注的工作大鼠心脏中，缺血（15分钟）会降低机械功能以及ATP和磷酸肌酸的组织水平，并增加乳酸和包括花生四烯酸在内的游离脂肪酸的组织水平。再灌注（20分钟）未能恢复机械功能，但除游离脂肪酸外，代谢物变化未完全恢复，游离脂肪酸在再灌注期间进一步变化。在缺血前5分钟给药直至缺血结束，或在再灌注后的前10分钟给药。消旋普萘洛尔和右旋普萘洛尔（10和30微摩尔）均会降低机械功能，加速缺血后再灌注期间机械功能的恢复，并减轻缺血再灌注诱导的代谢变化。当这些药物在再灌注期间存在时，对再灌注诱导的代谢变化的减轻更为明显。右旋普萘洛尔显示出与消旋普萘洛尔相似的心脏保护作用。噻吗洛尔（50微摩尔）在再灌注期间未加速机械功能的恢复，也未减轻再灌注诱导的代谢变化。这些结果表明，右旋普萘洛尔与消旋普萘洛尔一样，具有心脏保护作用，这可能归因于其膜稳定（或钠通道阻断）作用。
