Recent studies from our laboratory have documented several independent variables which control intrinsic AV nodal behavior including: absolute level of heart rate (HR), rate of change of HR change and time at a given HR. Our studies have shown that a particular cardiac cycle length is not associated with a fixed AV interval but rather, depends on both the magnitude and direction of HR change. Although modulated by neural tone and neurohumoral factors, the mechanism(s) by which rate-dependent properties are integrated with autonomic neural mechanisms is unknown. Indeed, it is clear that the AV node is richly innervated by autonomic nerves. The PURPOSE of the present proposal is to examine how the independent variables controlling intrinsic AV nodal behavior are modulated by sympathetic and parasympathetic neural activity. Specifically, we will investigate the HYPOTHESIS that a given level of neural activity will have variable efficacy on AV conduction depending upon the relative role(s) of each of the independent variables we have previously identified. The present experiments are directed toward an examination of how HR alterations influence in a specific and predictable fashion, subsequent impulse conduction through the AV node and how this influence might be modified and/or integrated by neural stimulation, neuromediators and/or ionic environment. Experiments will utilize on-line beat-by-beat graphic analysis of HR, AV interval, cycle length, change in cycle length, change in AV interval, etc. The sinus and AV node arteries will be catheterized and autologously perfused with blood from the femoral artery and with autonomic neuromediators and blockers in order to simulate activation or blockade, respectively of the sympathetic and/or parasympathetic nervous systems. This technique permits a separation of the rate-dependent properties of the AV node from those dependent on other modulatory factors. These studies are directed toward a more complete understanding of basic mechanisms which determine the propensity for cardiac impulses to propagate through the AV node. The data should have direct implications in furthering our understanding of both normal and pathophysiological AV nodal physiology. The information to be derived may provide presumptive information bearing upon the utility of different stimulation patterns to adequately assess AV nodal function in the human electrophysiologic laboratory.
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