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

Jeevaratnam, K, Zhang, Y, Guzadhur, L, Duehmke, RM, Lei, M, Grace, AA and Huang, CL (2010) Differences in sino-atrial and atrio-ventricular function with age and sex attributable to the Scn5a+/- mutation in a murine cardiac model. Acta Physiol (Oxf), 200 (1). pp. 23-33.

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Abstract

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(+/-).

Item Type:	Article
Authors :	Name Email ORCID Jeevaratnam, K k.jeevaratnam@surrey.ac.uk Zhang, Y Guzadhur, L Duehmke, RM Lei, M Grace, AA Huang, CL
Date :	September 2010
Identification Number :	10.1111/j.1748-1716.2010.02110.x
Uncontrolled Keywords :	Age Factors, Animals, Atrioventricular Node, Brugada Syndrome, Disease Models, Animal, Electrocardiography, Female, Genetic Predisposition to Disease, Male, Membrane Potentials, Mice, Mice, Knockout, Mutation, NAV1.5 Voltage-Gated Sodium Channel, Phenotype, Sex Factors, Sinoatrial Node, Sodium, Sodium Channels
Related URLs :	Author
Depositing User :	Symplectic Elements
Date Deposited :	17 May 2017 10:27
Last Modified :	17 May 2017 14:49
URI:	http://epubs.surrey.ac.uk/id/eprint/827849

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