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

Publication date: July 2018Source: Mechanisms of Ageing and Development, Volume 173Author(s): Shiraz Ahmad, Haseeb Valli, Karan R. Chadda, James Cranley, Kamalan Jeevaratnam, Christopher L.-H. HuangAbstractIntroductionAgeing and age-related bioenergetic conditions including obesity, diabetes mellitus and heart failure constitute clinical ventricular arrhythmic risk factors.Materials and methodsPro-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.Results and discussionYoung 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 ...
Source: Mechanisms of Ageing and Development - Category: Geriatrics Source Type: research