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This Article Full Text Full Text (PDF) All Versions of this Article: 295/3/H1270    most recent 00350.2008v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Mills, R. W. Articles by McCulloch, A. D. Search for Related Content PubMed PubMed Citation Articles by Mills, R. W. Articles by McCulloch, A. D.

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

Departments of ¹Bioengineering and ²Medicine, University of California-San Diego; ³Veterans Affairs Medical Center; and ⁴The 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 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.

mechanoelectric feedback; stretch-activated channels; resting membrane potential; electrical constants; membrane capacitance