The effect of antiarrhythmic drugs on life-threatening arrhythmias induced by the interaction between acute myocardial ischemia and sympathetic hyperactivity Transient myocardial ischemia, with attendant sympathetic hyperactivity, seems to play a major role in sudden cardiac death among patients with ischemic heart disease. Ventricular tachycardia (VT) and fibrillation (VF) are consistently and repeatedly elicited in cats by the interaction between a P-minute occlusion of the left descending coronary artery and a 30-second stimulation of the left stellate ganglion. When three consecutive trials yield almost identical results, time alone will not modify the response and a given drug can be injected to test its efficacy with an internal control analysis. In 90 cats the efficacy of the following drugs was assessed: lidocaine (n = ll), mexiletine (n = 12), propafenone (n = 12), propranolol (n = lQ), prarosin (n = lo), amiodarone (n = 14), and verapamil (n = 12). Class I antiarrhythmic drugs completely failed to afford protection and worsening of arrhythmia was observed in several instances. Propranolol and prazosin showed efficacy in approximately 80% and 60% of the animals, respectively. Amiodarone and verapamil completely prevented the onset of VT and VF. Protection from arrhythmias seems to be related to the combined presence of a noncompetitive adrenergic blockade associated with salutary effects on coronary circulation. These findings correlate with and help to explain the results of clinical trials in postmyocardial infarction patients. This model may help to provide a rational choice of antiarrhythmic drugs to be tested in clinical trials. (AM HEART J 109:937, 1985.) Peter J. Schwartz, M.D., Emilio Vanoli, M.D., Antonio Zaza, M.D., and Giulio Zuanetti, M.D. Milano, Italy The prevention of sustained ventricular tachycardia (VT) and ventricular fibrillation (VF) represents the key to reducing the incidence of sudden cardiac death in patients with coronary artery disease, but it is hindered by the fact that most of these deaths occur before the arrival of any medical assistance.’ Many patients die within minutes of the appearance of signs or symptoms of myocardial ischemia,2 while evidence of acute myocardial infarction is present in only a minority of patients resuscitated from out- of-hospital sudden death.’ On the other hand, results of analysis of Holter recordings from patients who die suddenly show growing evidence of the occurrence of an ischemic episode just prior to the fatal arrhythmia.3-6 Furthermore, those patients From the Unita per lo Studio delle Aritmie, Centro di Fisiologia Clinica e Ipertensione, Ospedale Maggiore, and the Istituto di Clinica Medica IV, Universita di Milano. Received for publication Sept. 5, 1984; revision received Nov. 8, 1984; accepted Dec. 20, 1984. Reprint requests: Peter J. Schwartz, M.D., Istituto di Clinica Medica IV, Pad. Sacco, Universita di Milano, Via F. Sforza 35, 20122 Milano, Italy. with an acute myocardial infarction, who were res- cued by a mobile coronary care unit and developed VF shortly afterward, had a clearcut increase in heart rate preceding the onset of VF.7 This evidence strongly supports the concept that elevated sympa- thetic activity and transient myocardial ischemia may precipitate many episodes of VF.’ Accordingly, a rational preventive strategy requires the identification of those drugs which, if administered prior to the acute ischemic event, may forestall the onset of malignant arrhythmias. Such an identification requires the availability of an animal model in which these arrhythmias can be reproducibly elicited by those stimuli which play a critical role in the genesis of sudden cardiac death. Acute myocardial ischemia activates cardiac sympa- thetic aBerent fibers9 and elicits an excitatory car- diocardiac sympathetic reflex.‘O The afferent limb of this sympathetic reflex is preferentially distributed through left-sided nerves,” whose arrhythmogenic potential has been well established.12 The increase in sympathetic activity, partly through a reflex inhibi- tion of the vagal outflow to the hear&l3 plays a major 937