Lu H, Remeysen P, De Clerck F
Department of Cardiovascular Pharmacology, Janssen Research Foundation, Beerse, Belgium.
Coron Artery Dis. 1993 Jul;4(7):649-57. doi: 10.1097/00019501-199307000-00010.
Single or multiple brief periods of myocardial ischemic preconditioning (PC) limits ischemia- and reperfusion-induced arrhythmias. This study tested whether PC protects against ischemia/reperfusion-induced arrhythmias and, if so, whether the protective effect was mediated by the opening of ATP-sensitive (KATP) channels.
In protocol 1, the effects of PC (three cycles of 2 minutes of coronary occlusion and 5 minutes of reperfusion) on the development of arrhythmias after a coronary occlusion of 5, 10, or 20 minutes followed by 10 minutes of reperfusion were studied in rats. In protocol 2, solvent or a KATP channel blocker (glyburide [0.64 mg/kg body weight delivered intravenously]) was administered 5 minutes before PC. In a second group, glyburide was administered immediately after PC. In a third group, solvent, glyburide, or a KATP channel opener (pinacidil [0.16 mg/kg delivered intravenously]) was administered 5 minutes before coronary occlusion for 5 minutes without PC.
In protocol 1, PC significantly reduced the ischemia-induced ventricular premature beats (VPBs) and ventricular tachycardia (VT), and it abolished ischemia-induced ventricular fibrillation (VF) during 10 or 20 minutes of coronary artery occlusion. PC also significantly reduced reperfusion-induced ventricular arrhythmias after 5 or 10 minutes of coronary artery occlusion; this effect of PC, however, was lost during reperfusion after 20 minutes of coronary occlusion. In protocol 2, PC again produced a marked reduction in reperfusion-induced arrhythmias and abolished the incidence of VPBs during 5 minutes of ischemia as well as the incidence of irreversible VF during reperfusion, whereas glyburide did not block the protective effect of PC on ischemia- and reperfusion-induced arrhythmias. Glyburide administered in non-PC animals did not reduce ischemia- and reperfusion-induced arrhythmias, nor did pinacidil.
The protective effect of PC was not attenuated by glyburide. These results suggest that the protective effect of PC in ischemia- and reperfusion-induced arrhythmias is not likely to be related to activation of KATP potassium channels during ischemia in rats.
单次或多次短暂的心肌缺血预处理（PC）可限制缺血和再灌注诱导的心律失常。本研究测试了PC是否能预防缺血/再灌注诱导的心律失常，如果可以，其保护作用是否由ATP敏感性（KATP）通道的开放介导。
在方案1中，研究了PC（三个周期，每个周期冠状动脉闭塞2分钟，再灌注5分钟）对大鼠冠状动脉闭塞5、10或20分钟后再灌注10分钟期间心律失常发生的影响。在方案2中，在PC前5分钟给予溶剂或KATP通道阻滞剂（格列本脲[静脉注射0.64mg/kg体重]）。在第二组中，在PC后立即给予格列本脲。在第三组中，在冠状动脉闭塞5分钟且无PC的情况下，在冠状动脉闭塞前5分钟给予溶剂、格列本脲或KATP通道开放剂（吡那地尔[静脉注射0.16mg/kg]）。
在方案1中，PC显著减少了缺血诱导的室性早搏（VPB）和室性心动过速（VT），并消除了冠状动脉闭塞10或20分钟期间缺血诱导的心室颤动（VF）。PC还显著减少了冠状动脉闭塞5或10分钟后的再灌注诱导的室性心律失常；然而，在冠状动脉闭塞20分钟后的再灌注期间，PC的这种作用消失了。在方案2中，PC再次显著减少了再灌注诱导的心律失常，并消除了缺血5分钟期间VPB的发生率以及再灌注期间不可逆VF的发生率，而格列本脲并未阻断PC对缺血和再灌注诱导的心律失常的保护作用。在未进行PC的动物中给予格列本脲并未减少缺血和再灌注诱导的心律失常，吡那地尔也没有。
格列本脲并未减弱PC的保护作用。这些结果表明，PC对缺血和再灌注诱导的心律失常的保护作用不太可能与大鼠缺血期间KATP钾通道的激活有关。
