title: Atrial structure, function and arrhythmogenesis in aged and frail mice.
abstract: Atrial fibrillation (AF) is prevalent in aging populations; however not all individuals age at the same rate. Instead, individuals of the same chronological age can vary in health status from fit to frail. Our objective was to determine the impacts of age and frailty on atrial function and arrhythmogenesis in mice using a frailty index (FI). Aged mice were more frail and demonstrated longer lasting AF compared to young mice. Consistent with this, aged mice showed longer P wave duration and PR intervals; however, both parameters showed substantial variability suggesting differences in health status among mice of similar chronological age. In agreement with this, P wave duration and PR interval were highly correlated with FI score. High resolution optical mapping of the atria demonstrated reduced conduction velocity and action potential duration in aged hearts that were also graded by FI score. Furthermore, aged mice had increased interstitial fibrosis along with changes in regulators of extracellular matrix remodelling, which also correlated with frailty. These experiments demonstrate that aging results in changes in atrial structure and function that create a substrate for atrial arrhythmias. Importantly, these changes were heterogeneous due to differences in health status, which could be identified using an FI.
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Hailey J
authors.initials: HJ
authors.lastname: Jansen
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Motahareh
authors.initials: M
authors.lastname: Moghtadaei
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Martin
authors.initials: M
authors.lastname: Mackasey
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Sara A
authors.initials: SA
authors.lastname: Rafferty
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Oleg
authors.initials: O
authors.lastname: Bogachev
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.|Division of Cardiology, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: John L
authors.initials: JL
authors.lastname: Sapp
authors.affiliation: Department of Pharmacology Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Susan E
authors.initials: SE
authors.lastname: Howlett
authors.affiliation: Department of Physiology and Biophysics, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.|School of Biomedical Engineering, Faculty of Medicine, Dalhousie University, Halifax, Nova Scotia, Canada.
authors.forename: Robert A
authors.initials: RA
authors.lastname: Rose
mesh_terms: D000200:Action Potentials / Q000502:physiology; D000375:Aging / Q000235:genetics*; D000818:Animals; D001281:Atrial Fibrillation / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D005355:Fibrosis; D000073496:Frailty / Q000000981:diagnostic imaging / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D015870:Gene Expression; D006325:Heart Atria / Q000000981:diagnostic imaging / Q000378:metabolism* / Q000473:pathology; D006334:Heart Function Tests; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D032383:Myocytes, Cardiac / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000235:genetics / Q000378:metabolism; D056969:Voltage-Sensitive Dye Imaging
chemical_list: D015415:Biomarkers; C000609875:COL3A1 protein, mouse; D024042:Collagen Type I; D000090602:Collagen Type I, alpha 1 Chain; D024061:Collagen Type III; D007527:Isoenzymes; C560825:Timp1 protein, mouse; D019715:Tissue Inhibitor of Metalloproteinase-1; D016212:Transforming Growth Factor beta; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse