Abstract 11162: Critical Window for Mechanically-Induced Arrhythmias Exists in Time and in Space
Introduction: Mechanical stimuli can cause premature ventricular excitation (PVEM) which, during a narrow time-window of the early T-wave, have been reported to result in re-entrant arrhythmias. We tested a computational modelling-based hypothesis that spatio-temporal overlap of a mechanical stimulus with the local repolarization wave-edge is required for re-entry, explaining the shorter critical window for mechanically-induced PVEM compared to electrical stimulation.
Methods: Epicardial mechanical stimuli were applied to the LV and RV freewall of Langendorff-perfused hearts from 1kg female rabbits (n=12). Coupling-interval was controlled from surface ECG R-wave. Optical voltage mapping was conducted (20μ L of 27.3mM di-4-ANBDQPQ) in mechanically-uncoupled hearts (10μ M blebbistatin). Fluorescence was excited by a red LED (640±10nm) and emission was collected by a 128×128 EMCCD at 511Hz (>690nm).
Results: Diastolic mechanical stimuli (<0.5mJ, 3.1mm2 contact area, ~2mm epicardial deformation) caused PVEM, which was reversibly attenuated by stretch-activated channel block (200nM GsMTx-4). As coupling interval was shortened, PVEM was seen until the early T-wave (Fig. A), when re-entry could arise (n=6) and lead to fibrillation (n=3). This occurred solely when the mechanically-affected tissue overlapped with the 50% repolarization isochrone (Fig B), as only then PVEM arose directly adjacent to unexcitable tissue that formed a region of functional block around which more than one re-entrant wave was generated (Fig C).
Conclusions: The requirement for spatio-temporal co-localization of mechanically-affected ventricular tissue and the repolarization wave gives rise to a regionally-varying arrhythmogenic coupling interval. The critical window for local mechanically-induced re-entry is therefore shorter than for more globally-effective electrical stimuli.
- © 2012 by American Heart Association, Inc.