Date of Award

Summer 7-2009

Degree Type

Restricted Access Dissertation

Degree Name

Doctor of Philosophy

Field of Study

Integrative Physiology

Department

Graduate School of Biomedical Sciences

First Advisor

Dr. Michael L. Smith

Abstract

Atrial fibrillation (AF) is the most common sustained arrhythmia in clinical practice and is an independent predictor of sudden cardiac death (SCD). AF is characterized by an irregular ventricular rhythm which may produce elevated sympathetic nerve activity (SNA) and increase the risk for SCD. However, limited data suggest that irregular ventricular rhythm during AF is inversely correlated with SCD. It is well established that increased vagal control reduces risk of SCD. However, it is unclear if the ventricular irregularity in AF is a function of vagal control. The purpose of this study was to determine if sinusoidal fluctuations in parasympathetic nerve activity on the ventricle result in an entrainment of the ventricular rhythm in both humans and porcine models of atrial fibrillation.

Forced vagal oscillations at two different frequencies were produced by employing deep breathing (0.125 Hz) and neck suction (0.25 Hz) in humans and pigs with AF. In the pig model, glycopyrrolate was administered to block peripheral muscarinic receptors, thus inhibiting vagal transmission to the heart. Heart rate variability was evaluated using power spectral analysis to determine the contribution of the vagus to ventricular irregularity in AF.

In all of our human subjects, power spectral analysis identified significant differences between oscillations in heart rhythm during neck suction (0.25Hz) and deep breathing (0.125 Hz) compared to baseline. In addition, the standard deviation of RR intervals was significantly different with neck suction compared to baseline. In our pig model, neck suction and deep breathing increased power at 0.25 and 0.15 Hz respectively and vagal blockade abolished power in both frequencies.

In humans and pigs, all frequency-mediated vagal maneuvers increased heart rate variability, suggesting the vagus does, in part, mediate ventricular irregularity during AF. These findings have important clinical implications considering the utility of heart rate variability analysis in patients with sinus rhythm. Reduced vagal tone, measured as heart rate variability, may be used to predict risk of sudden cardiac death in patients with AF.

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