el-Sherif N, Zeiler R H, Craelius W, Gough W B, Henkin R
Department of Medicine, State University of New York Health Science Center, Brooklyn 11203.
Circ Res. 1988 Aug;63(2):286-305. doi: 10.1161/01.res.63.2.286.
Polymorphic ventricular tachyarrhythmias occurred spontaneously during bradycardia in dogs given the inotropic polypeptide anthopleurin-A (AP-A). The arrhythmia was investigated in in vitro and in vivo experiments. In in vitro experiments, AP-A (50 micrograms/l) produced bradycardia-dependent prolongation of action potential duration that was more pronounced in Purkinje than in muscle fibers. Only Purkinje fibers developed early afterdepolarizations (EAD) and triggered activity. These effects could be abolished by rapid pacing, lidocaine (4 mg/l), or tetrodotoxin (1 mg/l). In vivo experiments were conducted in anesthetized healthy dogs with simultaneous recording of surface ECG, monophasic action potentials from the endocardial and epicardial surface of the left ventricle by contact electrode catheter technique, and transmembrane action potentials from the epicardial surface of the left ventricle with a floating microelectrode technique. AP-A in a dose comparable to that used in vitro (4 micrograms/kg, i.v. bolus) resulted in bradycardia-dependent marked prolongation of both monophasic and transmembrane action potentials. An EAD gradually appeared on both recordings but was more marked in endocardial monophasic action potentials. Eventually, a premature ventricular depolarization arose from or very close to the peak of the EAD. The prolongation of action potentials was associated with similar prolongation of the QTU interval in surface ECG, and in some experiments, the EAD corresponded to a distinct prominent U wave. A ventricular premature depolarization arose from the U or TU complex and initiated polymorphic ventricular tachyarrhythmias that terminated spontaneously or degenerated into ventricular fibrillation. These effects were reversed by rapid pacing or lidocaine (1 mg/kg). The present study provides evidence in support of the hypothesis that AP-A-induced ventricular tachyarrhythmias are due to bradycardia-dependent EAD and triggered activity.
给予正性肌力多肽类海葵素 - A（AP - A）的犬在心动过缓期间自发出现多形性室性心律失常。在体外和体内实验中对该心律失常进行了研究。在体外实验中，AP - A（50微克/升）导致动作电位时程出现心动过缓依赖性延长，这在浦肯野纤维中比在肌纤维中更明显。只有浦肯野纤维出现早期后除极（EAD）并引发激动。这些效应可通过快速起搏、利多卡因（4毫克/升）或河豚毒素（1毫克/升）消除。体内实验在麻醉的健康犬中进行，同时通过接触电极导管技术记录体表心电图、左心室内膜和心外膜表面的单相动作电位，以及使用漂浮微电极技术记录左心室心外膜表面的跨膜动作电位。与体外实验所用剂量相当的AP - A（4微克/千克，静脉推注）导致单相和跨膜动作电位出现心动过缓依赖性显著延长。在两种记录中逐渐出现EAD，但在心内膜单相动作电位中更明显。最终，一个室性早搏从EAD的峰值处或非常接近峰值处产生。动作电位的延长与体表心电图中QTU间期的类似延长相关，并且在一些实验中，EAD对应于一个明显突出的U波。一个室性早搏从U波或TU复合波处产生，并引发多形性室性心律失常，这些心律失常可自发终止或恶化为心室颤动。这些效应可通过快速起搏或利多卡因（1毫克/千克）逆转。本研究提供了证据支持以下假说：AP - A诱导的室性心律失常是由于心动过缓依赖性EAD和触发活动所致。
