Animal models for studying arrhythmogenic drug actions

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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.