Abstract 13098: Mechanically-Induced Premature Ventricular Excitation is Mediated by Cation Non-Selective Stretch-Activated Channels and Depends on the Extent of Local Tissue Deformation in Isolated Rabbit Heart
Introduction: Myocardial stretch can cause arrhythmia. The relative importance of local vs. global stimuli is unknown. We hypothesize that mechanically-induced premature ventricular excitation (PVE) is mediated by cation non-selective stretch-activated channels (SACNS), activated locally by tissue deformation.
Methods: Sub-contusional local mechanical stimuli were applied epicardially to LV and RV freewall of isolated rabbit hearts (n=7) using 3.1-28.3mm2 probes. Extent and rate of local tissue deformation, force, and pressure under the probe were recorded. Intraventricular pressure was measured by balloon and electrophysiology by ECG and optical voltage mapping (128×128pixels @ 511Hz). Intraventricular pressure spikes with dynamics mimicking those during local stimulation were applied separately, by balloon volume perturbation. Role of SACNS was tested by block with GsMTx-4. Effects were assessed by two-way ANOVA.
Results: Local mechanical stimuli of sufficient energy (0.01-0.48mJ) resulted in PVE, eliminated by 200nM GsMTx-4. PVE originated from stimulation sites and occurred at similar extents of tissue deformation (n=346 stimuli), regardless of location or probe contact area (deformation rate, force, and pressure under the probe were affected by both; Figure). Intraventricular pressure spikes from supra-threshold local stimulation (up to 14mmHg and 28ms) per se did not trigger PVE, as their application (even at 10×amplitude and 5×duration) had no effect.
Conclusions: Mechanically-induced PVE in isolated rabbit hearts requires SACNS. PVE induction threshold corresponds with the degree of local tissue deformation, but with neither local deformation rate, force, pressure, nor intra-ventricular pressure, supporting a role for regionally heterogeneous PVE initiation in mechanically-induced arrhythmogenesis. The apparent relevance of strain, rather than stress, in mechanical PVE induction deserves further investigation.
- © 2011 by American Heart Association, Inc.