Ventricular pro-arrhythmic phenotype, arrhythmic substrate, ageing and mitochondrial dysfunction in peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β-/-) murine hearts.

Mechanisms of Ageing and Development
Shiraz AhmadChristopher L-H Huang

Abstract

Ageing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors. Pro-arrhythmic properties in electrocardiographic and intracellular recordings were compared in young and aged, peroxisome proliferator-activated receptor-γ coactivator-1β knockout (Pgc-1β-/-) and wild type (WT), Langendorff-perfused murine hearts, during regular and programmed stimulation (PES), comparing results by two-way ANOVA. Young and aged Pgc-1β-/- showed higher frequencies and durations of arrhythmic episodes through wider PES coupling-interval ranges than WT. Both young and old, regularly-paced, Pgc-1β-/- hearts showed slowed maximum action potential (AP) upstrokes, (dV/dt)max (∼157 vs. 120-130 V s-1), prolonged AP latencies (by ∼20%) and shortened refractory periods (∼58 vs. 51 ms) but similar AP durations (∼50 ms at 90% recovery) compared to WT. However, Pgc-1β-/- genotype and age each influenced extrasystolic AP latencies during PES. Young and aged WT ventricles displayed distinct, but Pgc-1β-/- ventricles displayed similar dependences of AP latency upon (dV/dt)max resembling aged WT. They also independently increased myocardial fibrosis. AP wavelengths combi...Continue Reading

Citations

Aug 28, 2018·Journal of Cellular Physiology·Shiraz AhmadChristopher L-H Huang
Mar 5, 2021·Frontiers in Cardiovascular Medicine·Khalil Saadeh, Ibrahim Talal Fazmin
Apr 27, 2021·Molecular Genetics and Metabolism Reports·Khalil SaadehKamalan Jeevaratnam
Oct 14, 2021·Biochemical Society Transactions·Samantha C SalvageChristopher L-H Huang

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