Objective: Although the incidence of atrial fibrillation (AF) increases with age, the cellular electrophysiological changes that render the atria of aged individuals more susceptible to AF remain poorly understood. We hypothesized that dispersion of atrial repolarization increases with aging, creating a substrate for initiation of AF. Methods: Four groups of dogs were studied: adult and old dogs in normal sinus rhythm (SR) and adult and old dogs with chronic AF (CAF) induced by rapid atrial pacing. In each dog, action potentials (AP) were recorded with microelectrodes from isolated endocardial preparations of four regions of right atrium and three regions of left atrium. Two indices of AP duration (APD) heterogeneity were obtained in each dog by calculating standard deviation (SD) and the coefficient of variation (COV=[SD/mean]Â100%). Results: In SR groups, APD averaged across all regions was significantly longer in old than in adult tissues. Both indices of APD heterogeneity were higher in old dogs in comparison to adult. At both ages, CAF was associated with significant APD shortening and a decrease in APD adaptation to rate. While CAF significantly increased both indices of APD heterogeneity in adult dogs, it significantly decreased them in old dogs. Conclusions: The increase of spatial variability in repolarization in old atria may contribute to the initiation of AF in the aged. CAF-induced APD shortening and a decrease in APD adaptation appear to be important for the maintenance of sustained AF in both adult and old atria. The CAF-induced increase in dispersion of repolarization may be important for AF stabilization in adults, while previously reported fibrosis and slowed conduction of premature beats may be important in the old for both AF initiation during SR and subsequent stabilization of AF.

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Background-In depolarized myocardial infarct epicardial border zones, the cardiac sodium channel (SCN5A) is largely inactivated, contributing to low action potential upstroke velocity (V max ), slow conduction, and reentry. We hypothesized that a fast inward current such as the skeletal muscle sodium channel (SkM1) operating more effectively at depolarized membrane potentials might restore fast conduction in epicardial border zones and be antiarrhythmic. Methods and Results-Computer simulations were done with a modified Hund-Rudy model. Canine myocardial infarcts were created by coronary ligation. Adenovirus expressing SkM1 and green fluorescent protein or green fluorescent protein alone (sham) was injected into epicardial border zones. After 5 to 7 days, dogs were studied with epicardial mapping, programmed premature stimulation in vivo, and cellular electrophysiology in vitro. Infarct size was determined, and tissues were immunostained for SkM1 and green fluorescent protein. In the computational model, modest SkM1 expression preserved fast conduction at potentials as positive as Ϫ60 mV; overexpression of SCN5A did not. In vivo epicardial border zone electrograms were broad and fragmented in shams (31.5Ϯ2.3 ms) and narrower in SkM1 (22.6Ϯ2.8 ms; Pϭ0.03). Premature stimulation induced ventricular tachyarrhythmia/fibrillation Ͼ60 seconds in 6 of 8 shams versus 2 of 12 SkM1 (Pϭ0.02). Microelectrode studies of epicardial border zones from SkM1 showed membrane potentials equal to that of shams and V max greater than that of shams as membrane potential depolarized (PϽ0.01). Infarct sizes were similar (sham, 30Ϯ2.8%; SkM1, 30Ϯ2.6%; Pϭ0.86). SkM1 expression in injected epicardium was confirmed immunohistochemically. Conclusions-SkM1 increases V max of depolarized myocardium and reduces the incidence of inducible sustained ventricular tachyarrhythmia/fibrillation in canine infarcts. Gene therapy to normalize activation by increasing V max at depolarized potentials may be a promising antiarrhythmic strategy. Key Words: arrhythmia Ⅲ gene therapy Ⅲ ion channels Ⅲ myocardial infarction Ⅲ tachyarrhythmias R eentry accounts for Ϸ85% of serious arrhythmias complicating ischemic heart disease. 1 Prevention and treatment are rooted in early 20th century research on reentry. [2][3][4] The goals are to create bidirectional conduction block (with drugs that block Na ϩ channels, surgery, or ablation), to prolong refractoriness so that reentry fails (with drugs that usually prolong repolarization), or both in combination. 5 These therapies have drawbacks ranging from incomplete success to toxicity, including proarrhythmia. Editorial p 6 Clinical Perspective p 27Less attention has been paid to another therapeutic approach suggested many years ago 2-5 : reentry should terminate if an activating waveform persists in conducting at normal velocity, even through depolarized tissues. Therefore, we hypothesized that "improving" the efficiency of propagation through depolarized regions by increasing the maximum Received July 22, 2008; accep...

Immediately following RCDP interns had improved observed abilities and decreased time to perform critical interventions in NR simulation as compared to those trained with the simulation debriefing. RCDP was not superior in improving confidence level or retention.