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.
Full text not available from this repository.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 | ||||||||||||||||||||||||
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Divisions : | Surrey research (other units) | ||||||||||||||||||||||||
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Date : | September 2010 | ||||||||||||||||||||||||
DOI : | 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 | ||||||||||||||||||||||||
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Depositing User : | Symplectic Elements | ||||||||||||||||||||||||
Date Deposited : | 17 May 2017 10:27 | ||||||||||||||||||||||||
Last Modified : | 24 Jan 2020 19:20 | ||||||||||||||||||||||||
URI: | http://epubs.surrey.ac.uk/id/eprint/827849 |
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