Heisler B E, Ferrier G R
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
J Pharmacol Exp Ther. 1996 Oct;279(1):317-24.
Flecainide may increase the incidence of cardiac arrhythmias in acute ischemia. The objective of this study was to determine the cellular actions underlying this effect in an isolated tissue model of acute ischemia and reperfusion. Transmembrane electrical activity was recorded with conventional microelectrode techniques from epi- and endocardial surfaces of right ventricular free walls from guinea pig hearts. Endocardium was stimulated. Tissues were equilibrated in Tyrode's solution for 60 min, then exposed to simulated ischemia (hypoxia, acidosis, lactate, hyperkalemia, no glucose) for 15 min and reperfused with normal Tyrode's solution for 30 min. In the absence of flecainide, sustained and nonsustained ventricular tachycardia occurred in 78% of hearts during ischemic conditions and 78% in early reperfusion (n = 14). Premature beats occurred in 14% of hearts in early reperfusion. Ventricular tachycardia was associated with abbreviation of endocardial effective refractory period and action potential duration, plus prolongation of transmural conduction time. Flecainide abolished premature beats at a concentration of 1 mumol/l or higher. However, an increase in the incidence of ventricular tachycardia occurred in both ischemia and reperfusion at all concentrations of flecainide (0.03-10.0 mumol/l). Proarrhythmic effects of flecainide were associated with selective prolongation of transmural conduction time in ischemia and early reperfusion. In epicardial slices flecainide lengthened conduction time transverse, but not parallel to fiber orientation. Our results suggest that proarrhythmic effects of flecainide in acute ischemia and reperfusion are mediated by potentiation of the arrhythmogenic effects of ischemia on anisotropic properties of the myocardium.
氟卡尼可能会增加急性缺血时心律失常的发生率。本研究的目的是确定在急性缺血和再灌注的离体组织模型中这种作用的细胞机制。采用传统微电极技术记录豚鼠心脏右心室游离壁心外膜和心内膜表面的跨膜电活动。刺激心内膜。组织在台氏液中平衡60分钟，然后暴露于模拟缺血（缺氧、酸中毒、乳酸、高钾血症、无葡萄糖）15分钟，再用正常台氏液再灌注30分钟。在无氟卡尼的情况下，78%的心脏在缺血期间出现持续性和非持续性室性心动过速，78%在再灌注早期出现（n = 14）。14%的心脏在再灌注早期出现早搏。室性心动过速与心内膜有效不应期和动作电位时程缩短以及跨壁传导时间延长有关。氟卡尼在浓度为1 μmol/l或更高时可消除早搏。然而，在所有氟卡尼浓度（0.03 - 10.0 μmol/l）下，缺血和再灌注时室性心动过速的发生率均增加。氟卡尼的促心律失常作用与缺血和再灌注早期跨壁传导时间的选择性延长有关。在心外膜切片中，氟卡尼延长了横向而非平行于纤维方向的传导时间。我们的结果表明，氟卡尼在急性缺血和再灌注中的促心律失常作用是通过增强缺血对心肌各向异性特性的致心律失常作用介导的。
