|About the Book|
Acute regional ischemia following coronary occlusion is a major cause of lethal ventricular arrhythmias. The overall objective of this research is to use computational modeling of both electrical and mechanical behavior to investigate the trigger andMoreAcute regional ischemia following coronary occlusion is a major cause of lethal ventricular arrhythmias. The overall objective of this research is to use computational modeling of both electrical and mechanical behavior to investigate the trigger and substrate of spontaneous arrhythmias arising from electrophysiological and mechanical changes in acute regional ischemia.-Experimental studies suggested that cellular uncoupling, which occurs in the later phase of acute regional ischemia, may play an important role in arrhythmogenesis. A 3D slab was constructed comprising a surviving subepicardial layer coupled to a depolarized midmyocardium. Results reveal that heterogeneous uncoupling between these two layers leads to heterogeneous effective refractory period in the subepicardium, providing the reentry substrate.-To further investigate the mechanisms for initiation of reentry during acute regional ischemia phase 1B, simulations were conducted on a rabbit bi-ventricular model with realistic electrophysiological representation of acute regional ischemia. The main finding is that the degree of hyperkalemia in the surviving subepi- and subendocardium, the lateral width of border zone and the degree of uncoupling between the surviving layers and the midmyocardium determined the dispersion of refractoriness, conduction velocity and excitability, and therefore the inducibility of reentry.-Experiments suggest that mechanical dysfunction can trigger and also contribute to the maintenance of ischemia-related arrhythmogenesis. However, the underlying mechanism is unknown. Simulations on an electro-mechanical model of the rabbit ventricles with acute regional ischemia reveal that (1) stretch of the ischemic tissue by the surrounding normal tissue during contraction leads to increased strains and strain rates, causing mechanically-induced depolarizations in the ischemic region, the magnitude of which increases in direction from border zone to central ischemic zone- (2) despite smaller mechanically-induced depolarizations in border zone, mechanically-induced ventricular premature beats originate from the ischemic border in the subendocardium in the left ventricle, then travel fully intramurally until emerging from the ischemic border on the subepicardial surface- (3) the mechanically-induced sub-threshold depolarizations contribute to the arrhythmogenic substrate by further decreasing the already reduced-by-hyperkalemia local excitability, thus ultimately causing conduction block and slow retrograde conduction in the ischemic region, and resulting in reentry.