Tosaki A, Szerdahelyi P, Engelman R M, Das D K
University of Connecticut Health Center, School of Medicine, Farmington.
J Pharmacol Exp Ther. 1993 Dec;267(3):1355-62.
Cromakalim is a member of the new antihypertensive drug family possessing an action that involves an increased K efflux in vascular and cardiac muscle. We studied the contribution of opening of ATP-sensitive K channel to the development of reperfusion-induced arrhythmias and myocardial ion shifts, particularly that of Na, K, Ca and Mg in isolated rat hearts. After 30 min of global ischemia, cromakalim (1 to 30 microM) failed to reduce reperfusion arrhythmias. On the postischemic-reperfused myocardium in a subset of hearts unresponsive to reperfusion-induced arrhythmias (duration of ischemia was reduced to 25 min), cromakalim treatment was associated with a higher incidence of reperfusion ventricular fibrillation (VF) and ventricular tachycardia (VT) as compared to the controls (100% VF and 100% VT in treated vs. 41% VF and 50% VT in controls, P < .05). Proarrhythmic effects of cromakalim were also reflected in a maldistribution of myocardial ions. At concentrations of 3, 10 and 30 microM of glibenclamide, a K channel blocker, a significant reduction in the incidence of reperfusion-induced VF and VT was observed, and an attenuation in the maldistribution of myocardial ion contents induced by ischemia/reperfusion was found. The reduction in myocardial contractility was detected at relatively high concentrations (10 and 30 microM) in both cromakalim- and glibenclamide-treated groups. The proarrhythmic effect of cromakalim (30 microM) was abolished by 3 microM of glibenclamide, suggesting that the increased tendency to develop reperfusion arrhythmias is associated with the cromakalim-induced K efflux.(ABSTRACT TRUNCATED AT 250 WORDS)
克罗卡林是新型抗高血压药物家族的一员，其作用机制包括增加血管和心肌中的钾外流。我们研究了ATP敏感性钾通道开放对再灌注诱导的心律失常及心肌离子转移（特别是离体大鼠心脏中钠、钾、钙和镁离子的转移）的影响。在全心缺血30分钟后，克罗卡林（1至30微摩尔）未能减少再灌注心律失常。在一部分对再灌注诱导的心律失常无反应的心脏（缺血时间缩短至25分钟）的缺血后再灌注心肌中，与对照组相比，克罗卡林治疗组再灌注室颤（VF）和室性心动过速（VT）的发生率更高（治疗组VF和VT发生率均为100%，对照组分别为41%和50%，P<0.05）。克罗卡林的促心律失常作用还体现在心肌离子分布不均上。在3、10和30微摩尔格列本脲（一种钾通道阻滞剂）浓度下，观察到再灌注诱导的VF和VT发生率显著降低，且发现缺血/再灌注诱导的心肌离子含量分布不均有所减轻。在克罗卡林和格列本脲治疗组中，相对高浓度（10和30微摩尔）时均检测到心肌收缩力降低。3微摩尔格列本脲可消除克罗卡林（30微摩尔）的促心律失常作用，这表明再灌注心律失常发生倾向增加与克罗卡林诱导的钾外流有关。（摘要截断于250字）
