Ageing and several age-related chronic conditions including obesity, insulin resistance and hypertension are associated with mitochondrial dysfunction and represent independent risk factors for atrial fibrillation (AF).
Atrial arrhythmogenesis was investigated in Langendorff-perfused young (3-4 month) and aged (>12 month), wild type (WT) and peroxisome proliferator activated receptor-γ coactivator-1β deficient (Pgc-1β(-/-)) murine hearts modeling age-dependent chronic mitochondrial dysfunction during regular pacing and programmed electrical stimulation (PES).
The Pgc-1β(-/-) genotype was associated with a pro-arrhythmic phenotype progressing with age. Young and aged Pgc-1β(-/-) hearts showed compromised maximum action potential (AP) depolarization rates, (dV/dt)max, prolonged AP latencies reflecting slowed action potential (AP) conduction, similar effective refractory periods and baseline action potential durations (APD90) but shortened APD90 in APs in response to extrasystolic stimuli at short stimulation intervals. Electrical properties of APs triggering arrhythmia were similar in WT and Pgc-1β(-/-) hearts. Pgc-1β(-/-) hearts showed accelerated age-dependent fibrotic change relative to WT, with young Pgc-1β(-/-) hearts displaying similar fibrotic change as aged WT, and aged Pgc-1β(-/-) hearts the greatest fibrotic change. Mitochondrial deficits thus result in an arrhythmic substrate, through slowed AP conduction and altered repolarisation characteristics, arising from alterations in electrophysiological properties and accelerated structural change.
Pharmacology, Toxicology and Pharmaceutical Science
2
6%
Other
1
3%
Unknown
11
31%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 19 June 2018.
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#30,960,025
of 34,151,039 outputs
Outputs from Mechanisms of Ageing & Development
#1,738
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Outputs of similar age
#317,168
of 353,624 outputs
Outputs of similar age from Mechanisms of Ageing & Development
#16
of 19 outputs
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