A major cause of death in the United States is sudden cardiac death. Most of these people die from the rapid onset of ventricular arrhythmias which are the result of runaway electrical activity in the heart. Greater knowledge of the factors which foster ventricular arrhythmias will help us to identify people who are at risk for cardiac sudden death. We hypothesize that regional heterogeneity of sympathetic innervation results in heterogeneous distributions in beta receptor density and intracellular coupling, and that this heterogeneity is a substrate for arrhythmias. In order to investigate this hypothesis we intend to map the distribution of myocardial sympathetic nerve endings, perfusion and beta receptor density using autoradiography. We will then determine the effects of alterations in sympathetic innervation on the electrical stability of the heart by assessing the conduction, refractoriness, and inducibility of ventricular arrhythmia during states of increased autonomic tone. A correlation between heterogenous innervation and arrhythmogenesis will be clinically relevant in identifying people who are at higher risk for sudden cardiac death.
