Manning A S, Crome R, Isted K, Coltart D J, Hearse D J
Adv Myocardiol. 1985;6:515-28.
We have assessed the ability of several of the main groups of antiarrhythmic agents to modify the incidence of reperfusion-induced ventricular fibrillation in the isolated working rat heart preparation with transient coronary artery occlusion. Hearts were perfused with Krebs-Henseleit medium containing 5 microM epinephrine to provide some level of exogenous catecholamine support. Compounds selected were: the fast sodium channel inhibitors lignocaine (1 and 10 microM) and prenylamine (4 microM) (the latter also possessing slow calcium channel antagonistic actions); the beta-adrenergic blocking agents oxprenolol (1.2 microM), timolol (0.13 microM), metoprolol (1.0 microM), and acebutolol (5.6 microM); and the slow calcium channel antagonist nifedipine (0.05 and 0.5 microM). After 15 min of coronary artery occlusion, over 90% of control hearts fibrillated 30-60 sec after the onset of reperfusion. Drugs reduced this to the following: prenylamine, 0% (p less than 0.001); 1 microM lignocaine, 83%; 10 microM lignocaine, 33% (p less than 0.01); oxprenolol, 92% (NS); timolol, 92% (NS); metoprolol, 42% (p less than 0.01); acebutolol, 67% (p less than 0.05); 0.05 microM nifedipine, 83% (NS); and 0.5 microM nifedipine, 67% (NS). Thus, inhibition of the fast inward sodium channel with agents such as prenylamine and lignocaine, (when begun before coronary-artery occlusion) offers maximal protection against reperfusion-induced ventricular fibrillation, while beta-blockade with timolol and oxprenolol and slow calcium channel inhibition with nifedipine do not offer any significant protection. The beta-blocking agents metoprolol and acebutolol produce a partial reduction that may be due to a membrane-stabilizing action, rather than to beta-blockade.
我们评估了几类主要抗心律失常药物在短暂冠状动脉闭塞的离体工作大鼠心脏标本中改变再灌注诱导的心室颤动发生率的能力。心脏用含5微摩尔肾上腺素的克雷布斯 - 亨泽莱特培养基灌注，以提供一定水平的外源性儿茶酚胺支持。所选化合物如下：快速钠通道抑制剂利多卡因（1和10微摩尔）和普尼拉明（4微摩尔）（后者也具有慢钙通道拮抗作用）；β-肾上腺素能阻滞剂氧烯洛尔（1.2微摩尔）、噻吗洛尔（0.13微摩尔）、美托洛尔（1.0微摩尔）和醋丁洛尔（5.6微摩尔）；以及慢钙通道拮抗剂硝苯地平（0.05和0.5微摩尔）。冠状动脉闭塞15分钟后，超过90%的对照心脏在再灌注开始后30 - 60秒内发生颤动。药物将此发生率降低如下：普尼拉明，0%（p<0.001）；1微摩尔利多卡因，83%；10微摩尔利多卡因，33%（p<0.01）；氧烯洛尔，92%（无显著性差异）；噻吗洛尔，92%（无显著性差异）；美托洛尔，42%（p<0.01）；醋丁洛尔，67%（p<0.05）；0.05微摩尔硝苯地平，83%（无显著性差异）；0.5微摩尔硝苯地平，67%（无显著性差异）。因此，用普尼拉明和利多卡因等药物抑制快速内向钠通道（在冠状动脉闭塞前开始）可提供对再灌注诱导的心室颤动的最大保护，而用噻吗洛尔和氧烯洛尔进行β-阻断以及用硝苯地平抑制慢钙通道则不能提供任何显著保护。β-阻滞剂美托洛尔和醋丁洛尔产生部分降低，这可能是由于膜稳定作用，而非β-阻断作用。
