MODEL STUDIES OF THE ROLE OF MECANOSENSITIVE CURRENTS IN THE GENERATION OF CARDIAC-ARRHYTHMIAS

Mechano-electrical feedback is studied by incorporating linear, instan taneously activating mechano-sensitive conductances into single cardia c cell models, as well as one-and two-dimensional cardiac network mode ls. The models qualitatively reproduce effects of maintained mechanica l stretch on experimentally measured action potential characteristics such as amplitude, maximum diastolic potential, peak upstroke velocity , and conduction velocity. Models are also used to simulate stretch-in duced depolarizations, action potentials, and arrhythmias produced by pulsatile volume changes in left ventricle of dog. The mechano-sensiti ve conductance threshold for a stretch-induced action potential is clo sely related to the magnitude of the time-independent K+ current, I-Kl , which offsets inward mechano-sensitive current. Activation of mechan o-sensitive conductances in small, spatially localized region of cells can evoke graded depolarizations, propagating ectopic beats, and if t imed appropriately, spiral reentrant waves. Mechano-sensitive conducta nce changes required to evoke these responses are well within the phys iologically plausible range. Results therefore indicate that many mech ano-electrical feedback effects can be modeled using linear, instantan eously activating mechano-sensitive conductances. As an example of how stretch can occur in real human hearts, magnetic resonance images wit h saturation tagging are used to reconstruct the three-dimensional lef t ventricular wall motion. In patients with infarcts or recent ischemi c events, ''paradoxical deformation'' is observed in that regions of m yocardium are stretched rather than contracted during systole. In cont rast, normal hearts contract uniformly with no stretch during systole. Paradoxical deformations in ischemic hearts may therefore present one possible substrate for the mechanically induced arrhythmias modeled a bove. (C) 1998 Academic Press Limited.