Mechanisms of conduction slowing during myocardial stretch by ventricular volume loading in the rabbit

Abstract

Acute ventricular loading by volume inflation reversibly slows epicardial electrical conduction, but the underlying mechanism remains unclear. This study investigated the potential contributions of stretch-activated currents, alterations in resting membrane potential, or changes in intercellular resistance and membrane capacitance. Conduction velocity was assessed using optical mapping of isolated rabbit hearts at end-diastolic pressures of 0 and 30 mmHg. The addition of 50 microM Gd3+ (a stretch-activated channel blocker) to the perfusate had no effect on slowing. The effect of volume loading on conduction velocity was independent of changes in resting membrane potential created by altering the perfusate potassium concentration between 1.5 and 8 mM. Bidomain model analysis of optically recorded membrane potential responses to a unipolar stimulus suggested that the cross-fiber space constant and membrane capacitance both increased with loading (21%, P = 0.006, and 56%, P = 0.004, respectively), and these changes, when implemented in a resistively coupled one-dimensional network model, were consistent with the observed slowing (14%, P = 0.005). In conclusion, conduction slowing during ventricular volume loading is not attributable to stretch-activated currents or altered resting membrane potential, but a reduction of intercellular resistance with a concurrent increase of effective membrane capacitance results in a net slowing of conduction.

Biomechanics of Cardiac Electromechanical Coupling and Mechanoelectric Feedback

“…Such electrophysiological changes may contribute to susceptibility to reentrant arrhythmia in tissue regionally affected by disease or dyssynchrony [36,45,46,49,50]. Alterations in ion currents may explain the conduction changes observed in stretched tissue, although experiments showing no effect of stretch-activated channel blockers in tissue suggest otherwise [48,49]. Simulations based on these experiments suggest that this slowing may be linked to increased cell membrane capacitance with tissue stretch [49,51].…”

“…Additionally, changes in ventricular conduction dependent on hemodynamic load may also contribute to electrocardiogram-perceived changes in ventricular repolarization, by delaying the timing of depolarization globally, or offsetting it within a region. Experiments in intact and perfused rabbit hearts have shown conduction slowing with ventricular volume loading, a change which would increase apparent ventricular repolarization time [48,49]. Experiments in a variety of tissue preparations have yielded acceleration, deceleration, or biphasic changes in conduction velocity under several modalities of tissue stretch [47,49].…”

“…Experiments in intact and perfused rabbit hearts have shown conduction slowing with ventricular volume loading, a change which would increase apparent ventricular repolarization time [48,49]. Experiments in a variety of tissue preparations have yielded acceleration, deceleration, or biphasic changes in conduction velocity under several modalities of tissue stretch [47,49]. Such electrophysiological changes may contribute to susceptibility to reentrant arrhythmia in tissue regionally affected by disease or dyssynchrony [36,45,46,49,50].…”

“…Experiments in a variety of tissue preparations have yielded acceleration, deceleration, or biphasic changes in conduction velocity under several modalities of tissue stretch [47,49]. Such electrophysiological changes may contribute to susceptibility to reentrant arrhythmia in tissue regionally affected by disease or dyssynchrony [36,45,46,49,50]. Alterations in ion currents may explain the conduction changes observed in stretched tissue, although experiments showing no effect of stretch-activated channel blockers in tissue suggest otherwise [48,49].…”

Atrial Fibrillation and Heart Failure: How Should We Manage Our Patients?

“…Patients with HF develop an increase in left ventricular filling pressure secondary to either systolic or diastolic dysfunction. 6 Such changes lead to a remodelling of the left atrium, which in turn can act as a substrate for AF. HF patients also demonstrate altered calcium handling leading to calcium overload, which in turn can alter depolarisation patterns, resulting in arrhythmias.…”