Mechanisms and treatment of polymorphic ventricular tachycardia

1.本研究采用离体兔心脏灌流模型，探讨了电击诱发多形性室性心动过速（PVT）的机制及不同药物对PVT的影响.使用我们定制的光学记录系统，从用电压敏感染料（di-4-ANEPPS）染色的心室的8-32个心外膜部位记录荧光动作电位信号。常规记录具有高S/N比（> 50 dB）的稳定光信号，具有-3.6%/min的小基线漂移。在动作电位复极期应用直流电（10- 40 V）可引起动作电位延长和心室复极的空间离散度增加，从而引发兴奋的迂回运动，导致PVT。4.双相电击较单相电击心室复极离散度小，PVT发生率低，持续时间短. 10μM丙吡胺延长心室动作电位 关于我们 对心室传导速度的影响很小，而30 μM丙吡胺则显著降低心室传导速度。在存在10μM丙吡胺的情况下，DC电击诱导PVT的脆弱性略有降低。相反，在存在30μM丙吡胺的情况下，对PVT的易感性大大增加，诱导的PVT显示出比对照组更长的持续时间。E-4031（0.1μM）引起心室动作电位的反向频率依赖性延长，并且对PVT的易感性显著降低，持续时间更短。用异丙肾上腺素（0.1μM）刺激β肾上腺素能受体，导致动作电位缩短，并有相当大的区域差异。在异丙肾上腺素的存在下，PVT表现出比对照组更长的持续时间。结论：直流电击通过增强心室复极的空间不均匀性，引起PVT基础兴奋的迂回运动，药物诱导的ADP离散度可能促进和加重直流电击诱发的折返性快速性心律失常。少

1. In this study, we investigated mechanisms underlying DC shock-induced polymorphic ventricular tachycardia (PVT) and effects of various drugs on PVT in rabbit hearts perfused in vitro.2. Fluorescent action potential signals were recorded from 8-32 epicardial sites of ventricles stained with a voltage-sensitive dye (di-4-ANEPPS) with the use of our custom-built optical recording system. Stable optical signals with a high S/N ratio (>50dB) were routinely recorded with a small base-line drift of -3.6%/min.3. Application of DC shocks (10-40V) during the repolarization phase of action potentials caused a prolongation of action potentials and an enhancement of spatial dispersion of ventricular repolarization, giving rise to an initiation of circuitous movement of excitation leading to PVT.4. Biphasic shocks caused less dispersion of ventricular repolarization and lower incidence and shorter duration of PVT than monophasic shocks.5. 10μM disopyramide prolonged ventricular action potentials … More with minimal effects on conduction velocity, whereas 30 μM disopyramide decreased significantly ventricular conduction velocity. In the presence of 10μM disopyramide, vulnerability to PVT induction by DC shock was slightly reduced. In contrast, in the presence of 30μM disopyramide, vulnerability to PVT was greatly increased and induced PVT showed much longer perpetuation than controls. E-4031 (0.1μM) caused a reverse-frequency dependent prolongation of ventricular action potentials and a marked decrease in vulnerability to PVT with shorter perpetuation.6. Stimulation of β adorenergic receptor by isoproterenol (0.1μM) resulted in a shortening of action potentials with considerable regional differences. In the presence of isoproterenol, PVT showed longer perpetuation than controls.7. In conclusion, DC shocks initiate circuitous movement of excitation underlying PVT through an enhancement of spatial inhomogeneity of ventricular repolarization, and drug-induced in ADP dispersion may facilitate and exaggerate DC shock-induced reentrant tachyarrhythmias. Less