Mechanisms of Mechanically Induced Spontaneous Arrhythmias in Acute Regional Ischemia.
185 - U381.
Rationale: Although ventricular premature beats (VPBs) during acute regional ischemia have been linked to mechanical stretch of ischemic tissue, whether and how ischemia-induced mechanical dysfunction can induce VPBs and facilitate their degradation into reentrant arrhythmias has not been yet addressed.Objective: This study used a novel multiscale electromechanical model of the rabbit ventricles to investigate the origin of and the substrate for spontaneous arrhythmias arising from ischemia-induced electrophysiological and mechanical changes.Methods and Results: Two stages of ischemia were simulated. Dynamic mechanoelectrical feedback was modeled as spatially and temporally nonuniform membrane currents through mechanosensitive channels, the conductances of which depended on local strain rate. Our results reveal that both strains and strain rates were significantly larger in the central ischemic zone than in the border zone. However, in both ischemia stages, a VPB originated from the ischemic border in the left ventricular apical endocardium because of mechanically induced suprathreshold depolarizations. It then traveled fully intramurally until emerging from the ischemic border on the anterior epicardium. Reentry was formed only in the advanced ischemia stage as the result of a widened temporal excitable gap. Mechanically induced delayed afterdepolarization-like events contributed to the formation of reentry by further decreasing the already reduced-by-hyperkalemia local excitability, causing extended conduction block lines and slowed conduction in the ischemic region.Conclusions: Mechanically induced membrane depolarizations in the ischemic region are the mechanism by which mechanical activity contributes to both the origin of and substrate for spontaneous arrhythmias under the conditions of acute regional ischemia. (Circ Res. 2010; 106: 185-192.)
|Title:||Mechanisms of Mechanically Induced Spontaneous Arrhythmias in Acute Regional Ischemia|
|Keywords:||ventricular premature beats, acute ischemia, electromechanics, arrhythmias, ACTIVATED ION CHANNELS, ISOLATED RABBIT HEART, INDUCED VENTRICULAR-ARRHYTHMIAS, CORONARY-ARTERY-DISEASE, RAT CARDIAC MYOCYTES, MECHANOELECTRIC FEEDBACK, MYOCARDIAL-ISCHEMIA, GLOBAL-ISCHEMIA, PORCINE HEART, PIG-HEART|
|UCL classification:||UCL > School of Life and Medical Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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