Age‐dependent electrocardiographic changes in Pgc‐1β deficient murine hearts
| Autor: | Ahmad, Shiraz, Valli, Haseeb, Salvage, Samantha C, Grace, Andrew A, Jeevaratnam, Kamalan, Huang, Christopher L‐H |
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| Jazyk: | angličtina |
| Rok vydání: | 2017 |
| Předmět: |
Mice
Knockout Aging Original Articles electrocardiogram ECG peroxisome proliferator activated receptor‐γ‐coactivator‐1 (PGC‐1) Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha Electrocardiography Mice Gene Expression Regulation cardiac arrhythmias cardiac conduction Animals Original Article cardiovascular diseases |
| Zdroj: | Clinical and Experimental Pharmacology & Physiology |
| ISSN: | 1440-1681 0305-1870 |
| Popis: | Summary 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 have not been previously studied. Young (12‐16 weeks) and aged (>52 weeks), wild type (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 manifested 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 arrhythmogenicity in intact Pgc‐1β−/− systems in widespread cardiac regions. |
| Databáze: | OpenAIRE |
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