Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts.
Clinical and experimental pharmacology & physiology
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Ahmad, S., Valli, H., Salvage, S., Grace, A., Jeevaratnam, K., & Huang, C. (2018). Age-dependent electrocardiographic changes in Pgc-1β deficient murine hearts.. Clinical and experimental pharmacology & physiology, 45 (2), 174-186. https://doi.org/10.1111/1440-1681.12863
Increasing evidence implicates chronic energetic dysfunction in human cardiac arrhythmias. Mitochondrial impairment through Pgc-1β knockout is known to produce a murine arrhythmic phenotype. However, the cumulative effect of this with advancing age and its electrocardiographic basis has not been previously studied. Young (12-16 weeks) and aged (>52 weeks), WT (n = 5 and 8) and Pgc-1β-/- (n = 9 and 6), mice were anaesthetised and used for electrocardiographic (ECG) recordings. Time intervals separating successive ECG deflections were analysed for differences between groups before and after β1-adrenergic (intraperitoneal dobutamine 3 mg/kg) challenge. Heart rates before dobutamine challenge were indistinguishable between groups. The Pgc-1β-/- genotype however displayed compromised nodal function in response to adrenergic challenge. This manifest as an impaired heart rate response suggesting a functional defect at the level of the sino-atrial node, and a negative dromotropic response suggesting an atrioventricular conduction defect. Incidences of the latter were most pronounced in the aged Pgc-1β-/- mice. Moreover, Pgc-1β-/- mice displayed electrocardiographic features consistent with the existence of a pro-arrhythmic substrate. Firstly, ventricular activation was prolonged in these mice consistent with slowed action potential conduction and is reported here for the first time. Additionally, Pgc-1β-/- mice had shorter repolarisation intervals, These were likely attributable to altered K+ conductance properties, ultimately resulting in a shortened QTc interval, which is also known to be associated with increased arrhythmic risk. ECG analysis thus yielded electrophysiological findings bearing on potential arrhythmogenecity in intact Pgc-1β-/- systems in widespread cardiac regions.
Animals, Mice, Knockout, Mice, Electrocardiography, Gene Expression Regulation, Aging, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha
British Heart Foundation (PG/14/79/31102)
WELLCOME TRUST (105727/Z/14/Z)
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External DOI: https://doi.org/10.1111/1440-1681.12863
This record's URL: https://www.repository.cam.ac.uk/handle/1810/274967
Attribution 4.0 International
Licence URL: http://creativecommons.org/licenses/by/4.0/
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