The age‐dependence of atrial arrhythmogenicity in Scn5a+/‐ murine hearts reflects alterations in action potential propagation and recovery

Summary

1. The experiments investigated the effect of age upon atrial electrophysiological properties in Scn5a^+/‐ hearts used to model corresponding increases in atrial arrhythmic tendency in human Brugada Syndrome.
2. Atrial action potential initiation, propagation and recovery were compared in young (3 month) and aged (12 month), wild‐type (WT) and Scn5a^+/‐ hearts. Thus: (i) multi‐electrode array recordings assessed the spatial propagation of intrinsic electrical activity in superfused atrial preparations. (ii) Bipolar electrogram recordings (BEGs) measured basic cycle lengths (BCLs) in Langendorff preparations. Durations of electrogram activity (EGDs), during regular (S1) and extrasystolic (S2) stimulation during programmed electrical stimulation (PES), provided EGD ratios and atrial effective refractory periods (AERPs). (iii) monophasic recordings measured action potential durations (APDs).
3. Systematic statistical explorations for independent and interacting effects of age and the Scn5a^+/‐ condition demonstrated that both young and aged Scn5a^+/‐ mice showed slowed propagation of atrial excitation relative to corresponding WT with the greatest effects in the aged Scn5a^+/‐, which additionally showed increased intrinsic BCLs.
4. Young Scn5a^+/‐ showed greater electrogram duration (EGD) and EGD ratios, as well as APD/AERP ratios suggesting increased arrhythmic tendency compared to WT.
5. Aged Scn5a^+/‐ showed normal EGDs, EGD ratios and APDs, increased AERPs and smaller APD/AERP ratios.
6. These electrophysiological findings thus indicate increased atrial arrhythmogenicity with maximal effects upon both conduction and repolarization characteristics in young compared to aged Scn5a^+/‐ animals.

© 2012 The Authors Clinical and Experimental Pharmacology and Physiology © 2012 Blackwell Publishing Asia Pty Ltd