Damaged myocardium facilitates arrhythmogenesis in a canine model of Brugada syndrome

Fibrofatty changes in the epicardial myocardium constitute an arrhythmogenic substrate in Brugada syndrome (BrS). Additional acute myocardial injury may exacerbate the pathogenesis of BrS. Experimental tissue models of BrS induced by ion-channel-modulating agents typically use healthy perfused canine preparations. However, these preparations inherently contain acutely damaged myocardium along the cut edges, which may influence neighboring healthy cardiomyocytes through gap junctions.

We evaluated whether damaged myocardium functionally alters the repolarization properties of adjacent healthy myocardium under BrS conditions.

We analyzed epicardial action potentials (APs) in 15 canine right ventricles by using an optical mapping system during a drug-induced BrS model (pinacidil and pilsicainide). To assess the impact of damaged myocardium, we measured AP duration (APD), activation time, signal-to-noise ratio (S/N), and AP morphology in the central healthy region and in the peripheral region adjacent to the damaged cut edge. We defined damaged tissue as area with low S/N (<1) along the edge of the preparation.

After induction of the BrS model, significant electrophysiological differences were observed between the healthy and peripheral regions. The peripheral region showed shorter APD, greater APD dispersion, more pronounced AP heterogeneity, longer activation time, and lower S/N than did the healthy region. Premature phase 2 reentrant activations frequently arose in the peripheral region with shortened APD, and the resultant wavefronts propagated according to regional differences in refractory periods and conduction delay.

Damaged myocardium alters the electrophysiological properties of adjacent myocardial APs, creating repolarization heterogeneities, and contributes not only to conduction disturbances but also to repolarization abnormalities.