Patients with left ventricular hypertrophy (LVH) due to hypertension, aortic stenosis and hypertrophic cardiomyopathy frequently die suddenly, and ventricular tachyarrhythmias may be responsible. An increased vulnerability to ventricular tachyarrhythmia induction has been demonstrated in patients with hypertrophic cardiomyopathy and aortic stenosis, and in rats and cats with LVH. We will examine the vulnerability to ventricular tachyarrhythmia induction and spontaneous arrhythmias in a canine model of LVH produced by banding the ascending aorta. The characteristics and mechanisms of the induced arrhythmias will be investigated by assessing the response to pacing maneuvers and several antiarrhythmic drugs, by examining myocardial flow and by determining the electrical activation sequence using a multisite mapping system. Puppies, 8-14 weeks old will undergo aortic banding or a sham operation. At 3, 6, 9, and 12 months each animal will undergo 24-hour ECG monitoring, echocardiography and programmed stimulation using a stimulation protocol similar to that used clinically. The echograms will be used to estimate the left ventricular mass which will be correlated with the """"""""ease"""""""" of arrhythmia inducibility, and the frequency of spontaneous ventricular arrhythmias on the Holter recordings. The responses of the induced arrhythmias to single and double ventricular extrastimuli, and to rapid pacing will be examined at 12 months. The animals with inducible arrhythmias will undergo serial electropharmacologic testing at 12 months with procainamide, lidocaine, indecainide, propranolol, bretylium, verapamil, and placebo in separate sessions in random order. Myocardial flow during ventricular pacing at several rates will be measured in banded and control animals. A computerized multisite mapping system will be used to determine the epicardial, endocardial and intramural electrical activation sequence of the induced ventricular tachyarrhythmias.
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