During the past 5-10 years many studies in animals and patients have supported the concept that the coronary circulation is often adversely affected by cardiac hypertrophy. These studies have shown that six factors (type of ventricular hypertrophy, severity of hypertrophy, right ventricular versus left ventricular hypertrophy, duration of hypertrophy, age at onset, and species [human versus other mammal]) modulate the complex interaction between coronary vascular and cardiac muscle growth in cardiac hypertrophy. The focus of the experiments in this proposal relates to the effects of various clinicically relevant types of hypertrophy on the coronary circulation. The investigations will encompass patient and animal studies. Cardiac hypertrophy secondary to myocardial infarction, that is, reactive hypertrophy, will be examined because we postulate that abnormalities in the coronary circulation to the hypertropied muscle may contribute to the pathogenesis of additional infarctions. Because cardiac hypertrophy secondary to exercise training is emerging as a common entity as a consequence of national interest in physical fitness, we plan to study coronary reserve in hypertroiphied hearts that have developed as a consequence of predominately edurance or strength training. These two types of training produce different geometric types of left ventricular hypertrophy. Because preliminary studies in our laboratory suggest that cardiac hypertrophy secondary to thyrotoxicosis is the only form of hypertrophy in adult animals that improves the functional capacity of the coronary circulation, additional studies in this area will be pursued. Finally, because preliminary studies suggest that pressure-induced hypertrophy in cardiac muscle subjected to ischemia is particularly prone to develop lethal ventricular arrhythmias, we plan to explore electrophysiological mechanisms that may be responsible for these rhythm disturbances. In the aggregate these four groups of studies will further our understanding about the complex effects of cardiac hypertrophy on the coronary circulation and the electrical stability of the myocardium.
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