Bernauer W, Ernenputsch I
Department of Pharmacology, University of Freiburg, Federal Republic of Germany.
Naunyn Schmiedebergs Arch Pharmacol. 1988 Jul;338(1):88-95. doi: 10.1007/BF00168817.
In isolated perfused rat hearts reperfusion of the occluded left coronary artery led to arrhythmias, their severity depending on the duration of the foregoing period of myocardial ischaemia. Simultaneously, high activities of the myocardial enzyme creatine kinase (CK) were released into the perfusion fluid. Corynanthine, blocking mainly alpha 1-adrenoceptors, and rauwolscine, blocking mainly alpha 2-adrenoceptors, concentration-dependently antagonized the reperfusion-induced arrhythmias (3-30 mumol/l). The most severe kind of arrhythmia, i.e., ventricular fibrillation was completely prevented by 30 mumol/l of either drug. Also arrhythmias occurring already during the period of coronary occlusion were antagonized, as tested with corynanthine. The beta 1-adrenoceptor blocking agent metoprolol (1, and 10 mumol/l) had no effect at all against reperfusion arrhythmias, and the mainly alpha 1-adrenoceptor stimulating agent phenylephrine markedly increased the severity of these rhythm disturbances. The release of creatine kinase during the coronary reperfusion was significantly decreased by corynanthine, while the effect of rauwolscine was smaller and non-significant. Phenylephrine markedly increased the enzyme leakage from the myocardium. In all hearts the extent of the ischaemic and necrotic areas was determined. The percentage of the previously ischaemic area found necrotic at the end of the reperfusion, depended on the duration of the coronary occlusion. Corynanthine in a highly significant way decreased the area of myocardial necrosis, an effect obtained to some extent also with rauwolscine. The findings suggest that alpha-adrenoceptor stimulation is involved in the genesis of arrhythmias and myocardial damage associated with myocardial ischaemia and reperfusion. Possible mechanisms of action of corynanthine and rauwolscine are discussed, especially in view of the interrelationship between alpha-adrenoceptors and slow calcium channels.
在离体灌注大鼠心脏中，闭塞左冠状动脉后再灌注会导致心律失常，其严重程度取决于先前心肌缺血期的持续时间。同时，心肌酶肌酸激酶（CK）的高活性被释放到灌注液中。主要阻断α1 -肾上腺素能受体的育亨宾和主要阻断α2 -肾上腺素能受体的萝芙辛，呈浓度依赖性地拮抗再灌注诱导的心律失常（3 - 30 μmol/l）。两种药物30 μmol/l均可完全预防最严重的心律失常类型，即室颤。用育亨宾测试发现，在冠状动脉闭塞期间已经出现的心律失常也受到拮抗。β1 -肾上腺素能受体阻断剂美托洛尔（1和10 μmol/l）对再灌注心律失常完全没有作用，而主要刺激α1 -肾上腺素能受体的去氧肾上腺素显著增加了这些节律紊乱的严重程度。育亨宾显著降低了冠状动脉再灌注期间肌酸激酶的释放，而萝芙辛的作用较小且不显著。去氧肾上腺素显著增加了心肌酶的漏出。在所有心脏中均测定了缺血和坏死区域的范围。再灌注结束时发现先前缺血区域坏死的百分比取决于冠状动脉闭塞的持续时间。育亨宾极显著地减少了心肌坏死面积，萝芙辛在一定程度上也有此作用。这些发现表明，α -肾上腺素能受体刺激参与了与心肌缺血和再灌注相关的心律失常和心肌损伤的发生。讨论了育亨宾和萝芙辛可能的作用机制，特别是鉴于α -肾上腺素能受体与慢钙通道之间的相互关系。
