Cardiac Vagal Afferent Response in Rats during Cardiac Contractility Modulation (CCM)

Abstract

Congestive heart failure (CHF) is responsible for substantial cardiac morbidity and mortality. Cardiac Contractility Modulation (CCM) delivers non‐excitatory endocardial electrical pulses during the refractory period. CCM enhances cardiac contractility, ejection fraction, and quality of life in patients. The underlying mechanism of action for these benefits is not fully understood. Since similar impulses delivered to the gut increase muscle contraction leading to activation of vagal afferents, we tested the effect of CCM on vagal afferent activity in the heart.HypothesisCCM results in an increase in activity of cardiac vagal afferent nerves. Since CCM is non‐excitatory, we speculate that CCM reflexly activates vagal afferents via increases in contractility, reducing excessive efferent sympathetic tone in CHF.MethodsAdult male Sprague‐Dawley rats under pentobarbital anesthesia were instrumented for extracellular recordings of cardiac vagal afferent firing during CCM stimulation of the left ventricle (4V or 7.5V for 60s).ResultsIn 18 vagal nerve fibers with cardiac receptive fields, CCM produced an intensity dependent increase (p<0.05) in firing frequency of 10 fibers (4.2 ± 1.2 Hz at 7.5V vs. 1.4 ± 0.66 Hz at baseline). 6 neurons were not affected by CCM. In two neurons, 4V stimulation increased while 7.5V had no effect on single fiber firing.ConclusionCCM, a new therapy for CHF elicits activation of cardiac vagal afferents. This likely results from a reflex increase in regional contractility, contributing to the clinical benefit of CCM via an increase in vagal afferent and reduced sympathetic tone. Supported by Impulse Dynamics, Inc.