Life-threatening arrhythmias occur in patients with ischemic heart disease and are often refractory to drug or pacing therapy. Approximately 500,000 Americans succumb to sudden death each year, of which 70% are due to ventricular tachyarrhythmias. The purpose of this proposed investigation is to: 1) evaluate the electrophysiological mechanisms conducive to the initiation of these arrhythmias, and 2) attempt to devise a surgical technique for their ablation. Two canine models of chronic myocardial infarction will be used. The first, occlusion of a coronary artery with subsequent reperfusion is a means for producing non-uniform (heterogeneous) infarcts. The second, injection of vinyl latex into a coronary artery, with simultaneous embolization to collateral vessels, produces homogeneous (uniform) infarcts in the dog. This study aims to: 1) Determine whether heterogeneous infarctions, with multiple areas of surviving but compromised myocardial tissue, interdigitated with irreversibly damaged tissue, markedly heightens the susceptibility to ventricular tachyarrhythmias. Canines with homogeneous infarctions will be less susceptible to these arrhythmias. For this evaluation we will be assessing the difference between these two models with respect to: a) the inducibility of ventricular tachyarrhythmias, b) local electrophysiologic properties including excitability thresholds and refractory periods, c) determination of the anatomic length of the border between ischemic and normal tissue using fluorescent angiography, and d) morphology of the different infarcts by hematoxylin-eosin histology. (2) In subsequent experiments dogs with chronic heterogeneous infarcts susceptible to ventricular tachyarrhythmias will have vinyl latex embolization superimposed to determine if conversion to a more uniform infarction (although more extensive) lessens the susceptibility to arrhythmias. The other parameters will also be assessed to ascertain the homogeneity of the resultant infarction. 3) Finally, a clinically applicable method of creating homogeneous injury, employing cryoablation, will be used to evaluate the non-arrhythmogenicity of this technique. Here, uniform cryothermic damage to the myocardium will be evaluated employing the same parameters. 4) The conversion of canine models of previous arrhythmogenicity with heterogeneous infarcts will be attempted with cryoablation for the purpose of superimposing a homogeneous, non-arrhythmic lesion. Again, all four parameters will be assessed.
