Crome R, Hearse D J, Manning A S
J Cardiovasc Pharmacol. 1986 Nov-Dec;8(6):1249-56. doi: 10.1097/00005344-198611000-00023.
The effects of nifedipine against ischemia- and reperfusion-induced arrhythmias were investigated using anesthetized rats with transient coronary artery occlusion. Nifedipine (5 micrograms/kg i.v.) administered 10 min prior to occlusion significantly decreased the incidence of arrhythmias occurring during 20-min coronary occlusion. The incidence and duration of reperfusion-induced ventricular fibrillation and subsequent mortality following 5-min coronary occlusion were also significantly reduced by this intervention. However, administration of nifedipine 1 min prior to reperfusion afforded no protection against reperfusion arrhythmias. To investigate whether nifedipine possesses a true antiarrhythmic action or merely extends the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances, reperfusion was initiated after 3, 5, 7, 10, 20, and 30 min of ischemia. Nifedipine reduced the incidence of reperfusion-induced ventricular fibrillation after all ischemic intervals, with no change in the time of peak vulnerability to reperfusion arrhythmias. Measurements of coronary flow with 153Gadolinium microspheres indicated that flow within ischemic tissue relative to that in normal tissue was significantly increased by nifedipine. Thus, administration of nifedipine prior to occlusion affords a protective effect against ischemia- and reperfusion-induced arrhythmias, and this action is not due to extension of the ischemic duration prior to reperfusion resulting in maximal rhythm disturbances.
利用麻醉大鼠短暂冠状动脉闭塞模型,研究硝苯地平对缺血及再灌注诱发心律失常的影响。在闭塞前10分钟静脉注射硝苯地平(5微克/千克),可显著降低20分钟冠状动脉闭塞期间心律失常的发生率。这种干预还可显著降低5分钟冠状动脉闭塞后再灌注诱发心室颤动的发生率和持续时间以及随后的死亡率。然而,在再灌注前1分钟给予硝苯地平对再灌注心律失常无保护作用。为了研究硝苯地平是具有真正的抗心律失常作用还是仅仅延长再灌注前的缺血时间从而导致最大程度的节律紊乱,在缺血3、5、7、10、20和30分钟后开始再灌注。硝苯地平在所有缺血间隔后均降低了再灌注诱发心室颤动的发生率,对再灌注心律失常的易损高峰时间无影响。用153钆微球测量冠状动脉血流表明,硝苯地平可使缺血组织内的血流相对于正常组织显著增加。因此,在闭塞前给予硝苯地平对缺血及再灌注诱发的心律失常具有保护作用,且这种作用并非由于再灌注前缺血时间延长导致最大程度的节律紊乱。