Dage R C, Anderson B A, Mao S J, Koerner J E
Marion Merrell Dow Research Institute, Cincinnati, Ohio 45215.
J Cardiovasc Pharmacol. 1991 Jan;17(1):158-65. doi: 10.1097/00005344-199101000-00023.
The effects of probucol, a lipophilic antioxidant, on the myocardial dysfunction (stunning) observed during reperfusion after 15-min ischemia in rabbit heart were studied. Rabbits received food with or without 1% probucol for 3 weeks. They were then anesthetized and prepared for recording of myocardial segment shortening, arterial blood pressure (BP), left ventricular pressure (LVP), rate of development of LVP (dP/dt), and a lead II ECG. Regional myocardial ischemia was produced by acute occlusion of the first marginal branch of the left coronary artery. Myocardial segment shortening was depressed after reperfusion in control rabbits. In comparison, myocardial segment shortening was significantly greater in probucol-treated rabbits than in control rabbits during reperfusion, indicating a beneficial effect. No hemodynamic or ECG changes measured could explain this difference. The number of premature ventricular contractions was reduced in the probucol-treated group, although the incidence of ventricular tachycardia (VT) and ventricular fibrillation (VF) were not. Concentrations of probucol in serum and heart of five rabbits were 15.0 +/- 1.2 micrograms/ml and 17.5 +/- 2.5 micrograms/g (mean +/- SEM), respectively. Only probucol concentrations in the serum were positively correlated with the improvement in myocardial segment shortening (r = 0.91, p = 0.03). We conclude that a clinically relevant serum concentration of probucol reduces ischemia-induced myocardial stunning in the rabbit.
研究了亲脂性抗氧化剂普罗布考对兔心脏缺血15分钟后再灌注期间观察到的心肌功能障碍（顿抑）的影响。兔子喂食含或不含1%普罗布考的食物3周。然后将它们麻醉并准备记录心肌节段缩短、动脉血压（BP）、左心室压力（LVP）、LVP上升速率（dP/dt）和II导联心电图。通过急性闭塞左冠状动脉第一边缘支产生局部心肌缺血。对照兔再灌注后心肌节段缩短受到抑制。相比之下，普罗布考治疗组兔在再灌注期间心肌节段缩短明显大于对照组兔，表明有有益作用。所测的血流动力学或心电图变化均不能解释这种差异。普罗布考治疗组室性早搏数量减少，尽管室性心动过速（VT）和心室颤动（VF）的发生率未降低。5只兔子血清和心脏中的普罗布考浓度分别为15.0±1.2微克/毫升和17.5±2.5微克/克（平均值±标准误）。只有血清中的普罗布考浓度与心肌节段缩短的改善呈正相关（r = 0.91，p = 0.03）。我们得出结论，临床上相关的血清浓度普罗布考可减轻兔缺血诱导的心肌顿抑。
