Most studies on the late development of sustained ventricular tachycardia associated with the evolution of myocardial infarction in human patients by necessity rely on electrophysiologic evaluations associated with treatment and with anatomic studies post-mortem. Thus, the time course of electrophysiologic and anatomic changes in myocardial infarction is confounded by data derived from patients with varying clinical complications and disease etiology. Studies using canine models of healed infarcts exhibiting inducible sustained ventricular tachycardia are usually studied from 3 days to 6 weeks following experimental infarction, and thus they involve evaluating infarcts which are relatively new when compared to the age of infarct in which the bulk of human electrophysiologic data have been derived. It is our contention that infarcts evolve over a longer period, perhaps months to years. Also we are proposing that late development of ventricular tachycardia in humans as well as in canine models and the development of the electrophysiologic substrate supporting the arrhythmias have similar etiology. Our overall objective is to study the long term evolution of myocardial infarction in a canine model in terms of its changing anatomy and electrophysiology in order to understand what factors contribute to the susceptibility to ventricular tachycardia at various stages of the evolution of healed infarcts. Dogs will undergo experimental myocardial infarction by occlusion and reperfusion. The evolution of the infarct will be monitored noninvasively using magnetic resonance imaging and body surface electrocardiographic signal averaging. In addition, their susceptibility to ventricular arrhythmias will be tested using programmed electrical stimulation via an implanted ventricular electrode. At various times from 2 weeks to 4 years animals will be selected for acute electrophysiologic studies in vivo and in vitro as well as anatomic and histologic evaluation of the infarct. It is our hypotheses that there is a long term remodeling of infarct anatomy and that these late anatomic changes including aneurysm formation contribute to electrophysiologic changes leading to enhanced susceptibility to ventricular tachyarrhythmias. The arrhythmia's focus and characteristics changes as the infarct ages. The underlying mechanism of the late arrhythmias involves dissociated conduction and block due to disruption of cell-to-cell electrical continuity.
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