Rabkin S W, Friesen J M, Ferris J A, Fung H Y
J Pharmacol Exp Ther. 1979 Jul;210(1):43-50.
Toxic cardiomyopathy may result in fatal arrhythmias. To develop a model to study ventricular fibrillation and asystole, we investigated the effect of cantharidin in the production of cardiac arrhythmias and myocardial damage. Conscious albino rabbits, weighing between 1.8 to 2.8 kg received an intravenous bolus injection of cantharidin ranging from 0.6 to 1.9 mg/kg or a control injection of solvent. The electrocardiogram was continuously monitored on tape before and after injection for extended periods of time. Dose-related effects were observed with the following: 1) presence, magnitude and duration of ST depression after injection; 2) occurrence of fatal arrhythmias; 3) survival time (high doses were usually fatal within 3 hr); and 4) electron microscopic evidence of mitochondrial swelling, intramitochondrial granules and myofibrillar degeneration. The most common arrhythmias associated with the high doses of cantharidin were frequent ventricular ectopics, ventricular tachycardia, ventricular fibrillation or asytole. The arrhythmias could not be explained by alterations in blood pressure, electrolytes or blood gases. These findings show the cardiotoxic properties of cantharidin and its ability to produce fatal cardiac arrhythmias. Thus, it may serve as a model to study sudden death and the efficacy of antiarrhythmic drugs.
中毒性心肌病可能导致致命性心律失常。为了建立一个研究室颤和心搏停止的模型，我们研究了斑蝥素在引发心律失常和心肌损伤方面的作用。体重在1.8至2.8千克之间的清醒白化兔静脉推注0.6至1.9毫克/千克的斑蝥素或注射溶剂作为对照。注射前后长时间用磁带连续监测心电图。观察到与剂量相关的效应如下：1）注射后ST段压低的出现、程度和持续时间；2）致命性心律失常的发生；3）存活时间（高剂量通常在3小时内致命）；4）线粒体肿胀、线粒体内颗粒和肌原纤维变性的电子显微镜证据。与高剂量斑蝥素相关的最常见心律失常是频发室性早搏、室性心动过速、室颤或心搏停止。心律失常不能用血压、电解质或血气的改变来解释。这些发现表明了斑蝥素的心脏毒性特性及其产生致命性心律失常的能力。因此，它可作为研究猝死和抗心律失常药物疗效的模型。
