Tosaki A, Engelman D T, Engelman R M, Das D K
University of Connecticut Health Center, School of Medicine, Farmington, USA.
J Pharmacol Exp Ther. 1995 Dec;275(3):1115-23.
The incidence of reperfusion ventricular fibrillation (VF) and tachycardia (VT), heart function and the maldistribution of cardiac cations were studied in isolated ischemic/reperfused hearts obtained from streptozotocin-induced diabetic rats. Effects of an ATP-sensitive potassium (KATP) channel opener, cromakalim, and a KATP channel blocker, glibenclamide, also were studied. After 2 and 8 weeks of diabetes, hearts were isolated and subjected to 30 min of ischemia followed by reperfusion. After 2 weeks of diabetes, the incidence of VF and VT was reduced from their nondiabetic control values of 100 and 100 to 42% (P < .05) and 50% (P < .05), respectively. The reduction in VF and VT was not observed with progressive diabetes and after 8 weeks cardiac failure developed. In the 8-week diabetics, the development of cardiac failure was reflected in the aggravation of heart function (26, 16 and 17% reductions in aortic flow, left ventricular developed pressure and first derivative of developed pressure, respectively), and ion shifts (56 and 71% accumulation in cellular Na+ and Ca++, respectively, and 15% loss in cell K+) before the induction of ischemia. After ischemia/reperfusion, these changes were pronounced in diabetic groups. Cromakalim aggravated and glibenclamide attenuated the incidence of arrhythmias, contractile function and ion shifts induced by ischemia/reperfusion in diabetic hearts. The data show that the use of KATP channel openers as anti-ischemic agents may be of particular concern in the population of postinfarction diabetic patients who are known to be at high risk of sudden coronary death.
在从链脲佐菌素诱导的糖尿病大鼠获得的离体缺血/再灌注心脏中，研究了再灌注室颤（VF）和心动过速（VT）的发生率、心脏功能以及心脏阳离子的分布不均。还研究了ATP敏感性钾（KATP）通道开放剂克罗卡林和KATP通道阻滞剂格列本脲的作用。糖尿病2周和8周后，分离心脏并进行30分钟缺血然后再灌注。糖尿病2周后，VF和VT的发生率分别从非糖尿病对照组的100%和100%降至42%（P<0.05）和50%（P<0.05）。随着糖尿病进展未观察到VF和VT的减少，8周后出现心力衰竭。在8周糖尿病大鼠中，心力衰竭的发展表现为缺血诱导前心脏功能恶化（主动脉流量、左心室舒张末压和舒张末压一阶导数分别降低26%、16%和17%）以及离子转移（细胞内Na+和Ca++分别蓄积56%和71%，细胞内K+丢失15%）。缺血/再灌注后，这些变化在糖尿病组中更为明显。克罗卡林加重而格列本脲减轻糖尿病心脏缺血/再灌注诱导的心律失常发生率、收缩功能和离子转移。数据表明，对于已知有冠心病猝死高风险的心肌梗死后糖尿病患者群体，使用KATP通道开放剂作为抗缺血药物可能尤其值得关注。
