Animal models for studying arrhythmogenic drug actions

为了检查心脏药物，特别是抗心律失常药物和正性肌力药物的潜在致心律失常副作用，进行了两种类型的犬实验。使用24小时ECG监测，长期记录给予口服III类抗心律失常药物MS-551和司马利特的犬，均在约30%的犬中诱导室性早搏，但未诱导尖端扭转型室性心动过速（VT）等重度室性心动过速。在冠状动脉结扎、洋地黄中毒或氟烷肾上腺素联合诱导的犬室性心动过速模型中，新的正性肌力药物OPC-18790和NKH 477可加重氟烷肾上腺素室性心动过速，但可与洋地黄联合使用和在心肌缺血条件下使用。目前的方法无法检测药物的长期致瘤性，因此可能需要新的动物模型。

To examine potential arrhythmogenic side effects of cardiac drugs, especially those of antiarrhythmic drugs and positive inotropic drugs, two types of dog experiments were performed. Using the 24 hr ECG monitoring, long term recording of dogs given oral class III antiarrhythmic drugs, MS-551 and sematilide, both induced in about 30% of dogs premature ventricular contractions, but did not induce torsade de pointes like severe ventricular tachycardia (VT). Also using canine VT models, induced by either coronary ligation, digitalis toxication or halothane adrenaline combination, new positive inotropic drugs, OPC-18790 and NKH477, aggravated halothane adrenaline VT, but could be used with digitalis and under myocardial ischemic condition. Long term arrhythmogenic properties of drugs could not be examined using the present methods and new animal models may be needed for this purpose.