title: 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.
authors.affiliation: Department of Bioengineering, University of California-San Diego, 9500 Gilman Dr., La Jolla, CA 92093-0412, USA.
authors.forename: Robert W
authors.initials: RW
authors.lastname: Mills
authors.forename: Sanjiv M
authors.initials: SM
authors.lastname: Narayan
authors.forename: Andrew D
authors.initials: AD
authors.lastname: McCulloch
mesh_terms: D000465:Algorithms; D000818:Animals; D002306:Cardiac Volume / Q000502:physiology*; D005110:Extracellular Space / Q000378:metabolism; D005682:Gadolinium / Q000494:pharmacology; D006321:Heart / Q000502:physiology*; D006329:Heart Conduction System / Q000502:physiology*; D006352:Heart Ventricles; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000502:physiology; D008955:Models, Cardiovascular; D009200:Myocardial Contraction / Q000502:physiology*; D011188:Potassium / Q000378:metabolism; D011817:Rabbits; D018924:Vascular Capacitance / Q000502:physiology
chemical_list: D005682:Gadolinium; D011188:Potassium