Submitted on April 2, 2008
Revised on July 19, 2008
Accepted on July 21, 2008
Mechanisms of Conduction Slowing During Myocardial Stretch by Ventricular Volume Loading in Rabbit
Robert William Mills1, Sanjiv M. Narayan2, and Andrew D. McCulloch3*
1 University of California, San Diego
2 University of California and Veterans Administration Medical Center, San Diego
3 University of California-San Diego
* To whom correspondence should be addressed. E-mail: amcculloch{at}ucsd.edu.
Background: Acute ventricular loading by volume inflation reversibly slows epicardial electrical conduction, but the underlying mechanism remains unclear. These studies investigate the potential contributions of stretch-activated currents, alterations in resting membrane potential, or changes in intercellular resistance and membrane capacitance. Methods and Results: Conduction velocity was assessed using optical mapping of isolated rabbit hearts at end-diastolic pressures of 0 and 30 mmHg. Addition of 50 µM gadolinium3+ (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 perfusate potassium concentration between 1.5 and 8 mM. Bidomain model analysis of optically-recorded membrane potential response to a unipolar stimulus suggests that cross-fiber space constant and membrane capacitance both increase with loading (21%, p = 0.006 and 56%, p = 0.004 respectively), and these changes when implemented in a resistively coupled 1-D network model are consistent with the observed slowing (14%, p = 0.005). Conclusions: 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.
