Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/- mutation in a murine cardiac model

作者：Jeevaratnam K; Zhang Y; Guzadhur L; Duehmke R M; Lei M; Grace A A; Huang C L H^*

来源：Acta Physiologica, 2010, 200(1): 23-33.

DOI：10.1111/j.1748-1716.2010.02110.x

• age
• electrophysiology
• sex
• sodium channel
• transgenic mice

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 effects. The latter suggest alterations in cardiac pacemaker function, atrio-ventricular conduction and ventricular repolarization greatest in ageing male Scn5a+/-.

• 出版日期2010-9
• 单位西安交通大学