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

• Published in: American journal of physiology. Heart and circulatory physiology 2008-09, Vol.295 (3), p.H1270-H1278
• Main Authors: Mills, Robert W, Narayan, Sanjiv M, McCulloch, Andrew D
• Format: Article
• Language: English
• Subjects: Algorithms; Animals; Cardiac Volume - physiology; Effects; Extracellular Space - metabolism; Gadolinium - pharmacology; Heart; Heart - physiology; Heart Conduction System - physiology; Heart Ventricles; In Vitro Techniques; Membrane Potentials - physiology; Models, Cardiovascular; Myocardial Contraction - physiology; Potassium - metabolism; Rabbits; Studies; Vascular Capacitance - physiology
• ISSN: 0363-6135; 1522-1539
• DOI: 10.1152/ajpheart.00350.2008

Departments of 1 Bioengineering and 2 Medicine, University of California-San Diego; 3 Veterans Affairs Medical Center; and 4 The Whitaker Institute of Biomedical Engineering, University of California-San Diego, La Jolla, California Submitted 2 April 2008 ; accepted in final form 21 July 2008 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 µM Gd 3+ (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. mechanoelectric feedback; stretch-activated channels; resting membrane potential; electrical constants; membrane capacitance Address for reprint requests and other correspondence: A. D. McCulloch, Dept. of Bioengineering, Univ. of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0412 (e-mail: amcculloch{at}ucsd.edu )