Diminished parasympathetic tone is associated with increased mortality. The risk of sudden death is increased during exercise. Exercise is also associated with diminished parasympathetic tone, raising the question whether parasympathetic tone may provide a natural anti-arrhythmic effect. Thus, the aim of the proposed studies is to address the question: What is the role of parasympathetic tone in modulating cardiac electrophysiology during exercise and recovery? Specific hypotheses are: a) recovery of heart rate and ventricular repolarization after exercise is mediated by sympathetic withdrawal, parasympathetic activation, and sympathetic-parasympathetic interactions -- this will be assessed by sequential autonomic blockade during serial bicycle exercise tests; b) there is diminished parasympathetic effect on recovery of heart rate and QT interval in subjects with coronary artery disease and left ventricular dysfunction -- this will be assessed by serial exercise tests with and without parasympathetic blockade; c) a new index of heart rate variability during recovery correlates with parasympathetic effects on recovery of heart rate and QT interval; d) parasympathetic effects on cardiac electrophysiology persist during exercise and are depressed in subjects with decreased versus normal left ventricular function -- this will be assessed by noninvasive programmed stimulation via implanted devices during sedal exercise testing with and without parasympathetic blockade; e) parasympathetic effects on the QT interval during exercise and recovery correlate with parasympathetic effects on ventricular refractoriness. Validation of these hypotheses will show: 1) parasympathetic tone modulates ventricular repolarization and refractoriness during exercise and recovery; 2) this modulation is suppressed in subjects with left ventricular dysfunction. Understanding the role of parasympathetic tone in modulating cardiac electrophysiology during exercise and recovery will open up a new avenue of research relating autonomic tone and sudden death. If parasympathetic tone does provide an antiarrhythmic effect during exercise and recovery, one could consider developing vagal nerve stimulation during exercise and recovery as a new treatment modality to prevent sudden death.
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