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• W2753452788 abstract "Abstract Long QT Syndrome 3 (LQTS3) arises from gain-of-function Na v 1.5 mutations, prolonging action potential repolarisation and electrocardiographic (ECG) QT interval, associated with increased age-dependent risk for major arrhythmic events, and paradoxical responses to β-adrenergic agents. We investigated for independent and interacting effects of age and S cn5a + /ΔKPQ genotype in anaesthetised mice modelling LQTS3 on ECG phenotypes before and following β-agonist challenge, and upon fibrotic change. Prolonged ventricular recovery was independently associated with S cn5a + /ΔKPQ and age. Ventricular activation was prolonged in old S cn5a + /ΔKPQ mice (p = 0.03). We associated S cn5a + /ΔKPQ with increased atrial and ventricular fibrosis (both: p < 0.001). Ventricles also showed increased fibrosis with age (p < 0.001). Age and S cn5a + /ΔKPQ interacted in increasing incidences of repolarisation alternans (p = 0.02). Dobutamine increased ventricular rate (p < 0.001) and reduced both atrioventricular conduction (PR segment-p = 0.02; PR interval-p = 0.02) and incidences of repolarisation alternans (p < 0.001) in all mice. However, in S cn5a + /ΔKPQ mice, dobutamine delayed the changes in ventricular repolarisation following corresponding increases in ventricular rate. The present findings implicate interactions between age and S cn5a + /ΔKPQ in prolonging ventricular activation, correlating them with fibrotic change for the first time, adding activation abnormalities to established recovery abnormalities in LQTS3. These findings, together with dynamic electrophysiological responses to β-adrenergic challenge, have therapeutic implications for ageing LQTS patients." @default.
• W2753452788 created "2017-09-15" @default.
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• W2753452788 date "2017-09-11" @default.
• W2753452788 modified "2023-09-24" @default.
• W2753452788 title "The effects of ageing and adrenergic challenge on electrocardiographic phenotypes in a murine model of long QT syndrome type 3" @default.
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• W2753452788 doi "https://doi.org/10.1038/s41598-017-11210-3" @default.
• W2753452788 hasPubMedCentralId "https://www.ncbi.nlm.nih.gov/pmc/articles/5593918" @default.
• W2753452788 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/28894151" @default.
• W2753452788 hasPublicationYear "2017" @default.
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