Varon D, Rechavi M, Erez M, Goldberg G, Manoach M, Kaverina N V
Department of Physiology and Pharmacology, Tel Aviv University School of Medicine, Israel.
J Basic Clin Physiol Pharmacol. 1993 Oct-Dec;4(4):299-311. doi: 10.1515/jbcpp.1993.4.4.299.
Ventricular fibrillation (VF) is a life-threatening arrhythmia that leads to death unless electrical defibrillation is applied in time. Recent publications indicate that VF can be either sustained (SVF), requiring electrical defibrillation, or transient (TVF), reverting spontaneously into sinus rhythm. Since VF cannot be totally prevented by drugs, a new antiarrhythmic therapeutic approach has been proposed: drug-induced enhancement of the ability of the heart to defibrillate by itself. In this study we examined the defibrillating potency of two antiarrhythmic phenothiazines, ethmozine (ETM) and ethacizine (ETA), as well as their effects on catecholamine uptake and on the electrophysiological properties of the myocardial cell membrane. The antiarrhythmic-defibrillatory activity was examined in cats; the inhibitory effect on [3H]-norepinephrine (NE) uptake was examined in rat brain synaptosomes, and the electrophysiological membrane effects were examined by microelectrode recordings in perfused strips of heart ventricle from guinea-pigs. The results indicate that: 1. ETA exhibits similar but stronger antiarrhythmic-defibrillating and NE reuptake inhibitory effects than ETM; 2. ETA at 10-6 M decreases ventricular conduction time and increases Vmax while ETM at this concentration does not change them; 3. The defibrillating ability of the drugs can be related to their inhibitory potency on NE reuptake. We suggest that the risk of sympathomimetic arrhythmogenicity is prevented by the previously described, membrane stabilizing Class 1 antiarrhythmic properties of these drugs.
心室颤动（VF）是一种危及生命的心律失常，若不及时进行电除颤会导致死亡。近期的出版物表明，VF可分为持续性（SVF），需要电除颤，或短暂性（TVF），可自发恢复为窦性心律。由于药物无法完全预防VF，因此提出了一种新的抗心律失常治疗方法：药物诱导增强心脏自身的除颤能力。在本研究中，我们检测了两种抗心律失常吩噻嗪类药物乙吗噻嗪（ETM）和依卡嗪（ETA）的除颤效力，以及它们对儿茶酚胺摄取和心肌细胞膜电生理特性的影响。在猫身上检测抗心律失常-除颤活性；在大鼠脑突触体中检测对[3H]-去甲肾上腺素（NE）摄取的抑制作用，并通过豚鼠离体心室肌条微电极记录检测电生理膜效应。结果表明：1. ETA表现出与ETM相似但更强的抗心律失常-除颤和NE再摄取抑制作用；2. 10-6 M的ETA可缩短心室传导时间并增加Vmax，而该浓度的ETM则无此作用；3. 药物的除颤能力可能与其对NE再摄取的抑制效力有关。我们认为，这些药物先前所述的1类抗心律失常膜稳定特性可预防拟交感神经致心律失常的风险。
