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Aim: To investigate the interacting effects of age and sex on electrocardiographic (ECG) features of Scn5a +/- mice modelling Brugada syndrome. Methods: Recordings were performed on anaesthetized wild-type (WT) and Scn5a +/- mice and differences attributable to these risk factors statistically stratified. Results: Scn5a +/- exerted sex-dependent effects upon sino-atrial function that only became apparent with age. RR intervals were greater in old male than in old female Scn5a +/- . Atrio-ventricular (AV) conduction was slower in young female mice, whether WT and Scn5a +/- , than the corresponding young male WT and Scn5a +/- . However, PR intervals lengthened with age in male but not in female Scn5a +/- giving the greatest PR intervals in old male Scn5a +/- compared with either old male WT or young male Scn5a +/- mice. In contrast, PR intervals were similar in old female Scn5a +/- and in old female WT. QTc was prolonged in Scn5a +/- compared with WT, and female Scn5a +/- compared with female WT. Age-dependent alterations in durations of ventricular repolarization relative to WT affected male but not female Scn5a +/- . Thus, T-wave durations were greater in old male Scn5a +/- compared with old male WT, but indistinguishable between old female Scn5a +/- and old female WT. Finally, analysis for combined interactions of genotype, age and sex demonstrated no effects on P wave and QRS durations and QTc intervals. Conclusion: We demonstrate for the first time that age, sex and genotype exert both independent and interacting ECG e ffects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a +/- . © 2010 Scandinavian Physiological Society.

Original publication

DOI

10.1111/j.1748-1716.2010.02110.x

Type

Journal article

Journal

Acta Physiologica

Publication Date

01/09/2010

Volume

200

Pages

23 - 33