Mechanism of ventricular defibrillation. The role of tissue geometry in the changes in transmembrane potential in patterned myocyte cultures.

Abstract

The geometry of the myocardium may influence changes in transmembrane potential (DeltaVm) during defibrillation. To test this hypothesis, specific nonlinear structures (bifurcations, expansions, and curved strands or "bends") were created in patterned cultures of neonatal rat myocytes. Extracellular field stimuli (EFS; 7 to 11 V/cm field strength) were applied parallel to the strands. Changes in Vm were measured with microscopic resolution using optical mapping techniques. In bifurcations, EFS produced 2 DeltaVm maxima (so-called secondary sources) at the shoulder of each limb that were separated by a decrease of either hyperpolarization or depolarization at the insertion of the stem strand. In expansions, EFS produced a significant decrease in DeltaVm at the insertion site of the expansion compared with the DeltaVm maxima measured at the lateral borders. In 50% of experiments, tertiary sources of opposite polarity appeared in the strand due to local electrotonic currents. New action potentials were propagated from the sites of DeltaVm maxima located at the lateral borders of the expansions. In bends, the strand oriented in parallel to the field dominated electrotonically and partially cancelled the sources produced by the perpendicular segment. In electrically well-coupled nonlinear structures, EFS produced changes in Vm at resistive boundaries that were determined by the electrotonic interaction between sources of different, direction-dependent strength. In addition, the interaction between localized secondary sources at nonlinear boundaries generated local current circuits, which gave rise to further changes in Vm (tertiary sources).