Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1β-/- hearts: effects of age.
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Valli, H., Ahmad, S., Fraser, J. A., Jeevaratnam, K., & Huang, C. L. (2017). Pro-arrhythmic atrial phenotypes in incrementally paced murine Pgc1β-/- hearts: effects of age.. Experimental physiology, 102 (12), 1619-1634. https://doi.org/10.1113/ep086589
Atrial arrhythmias, most commonly manifesting as atrial fibrillation (AF), represent a major clinical problem. AF incidences increase with both age and conditions associated with energetic dysfunction. Atrial arrhythmic phenotypes were compared in young (12-16 week) and aged (>52 week), WT and peroxisome proliferator receptor gamma co-activator 1β-deficient (Pgc-1β-/-), Langendorff-perfused hearts, previously used to model mitochondrial energetic disorder. Electrophysiological explorations were performed using simultaneous whole-heart electrocardiogram and intracellular atrial action potential (AP) recordings. Two stimulation protocols were employed: an S1S2 protocol which imposed extrasystolic stimuli at successively decremented intervals following regular pulse trains and a regular pacing protocol at successively incremented frequencies. Aged Pgc-1β-/- hearts showed greater atrial arrhythmogenicity, presenting as atrial tachycardia and ectopic activity. Maximum rates of AP depolarisation, (dV/dt)max, were reduced in Pgc-1β-/- hearts. AP latencies were increased by the Pgc-1β-/- genotype with an added interactive effect of age. In contrast, AP durations to 90% recovery (APD90) were shorter in Pgc-1β-/- hearts despite similar atrial effective recovery periods amongst the different groups. These findings accompanied paradoxical decreases in alternans incidence and duration in the aged and Pgc-1β-/- hearts. Limiting slopes of restitution curves of APD90 against diastolic interval were correspondingly interactively reduced by Pgc1β-/- genotype and age. In contrast, reduced AP wavelengths were associated with Pgc-1β-/- genotype both independently, and interacting with age, through the basic cycle lengths explored, with the aged Pgc-1β-/- showing the shortest wavelengths. These findings thus implicate AP wavelength in possible mechanisms for the atrial arrhythmic changes reported here.
British Heart Foundation (None)
Wellcome Trust (105727/Z/14/Z)
External DOI: https://doi.org/10.1113/ep086589
This record's URL: https://www.repository.cam.ac.uk/handle/1810/271054
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