Chronic angiotensin-converting enzyme inhibition attenuates frailty and protects against atrial fibrillation in aging mice.
Heart Rhythm
; 2024 Jul 15.
Article
em En
| MEDLINE
| ID: mdl-39019387
ABSTRACT
BACKGROUND:
Aging is a major risk factor for atrial fibrillation (AF); however, not all individuals age at the same rate. Frailty, which is a measure of susceptibility to adverse health outcomes, can be quantified with a frailty index (FI).OBJECTIVE:
This study aimed to determine the effects of angiotensin-converting enzyme (ACE) inhibition on AF and atrial remodeling in aging and frail mice.METHODS:
Aging mice were treated with the ACE inhibitor enalapril for 6 months beginning at 16.5 months of age and frailty was quantified. AF susceptibility and atrial structure and function were assessed by intracardiac electrophysiology in anesthetized mice, high-resolution optical mapping in intact atrial preparations, patch clamping in isolated atrial myocytes, and histology and molecular biology in atrial tissues.RESULTS:
Enalapril attenuated frailty in aging mice with larger effects in females. AF susceptibility was increased in aging mice but attenuated by enalapril. AF susceptibility and duration also increased as a function of FI score. P-wave duration was increased and atrial conduction velocity was reduced in aging mice and improved after enalapril treatment. Furthermore, P-wave duration and atrial conduction velocity were strongly correlated with FI score. Atrial action potential upstroke velocity (Vmax) and Na+ current (INa) were reduced whereas atrial fibrosis was increased in aging mice. Action potential Vmax, INa, and fibrosis were improved by enalapril and also correlated with FI scores.CONCLUSION:
ACE inhibition with enalapril attenuates frailty and reduces AF susceptibility in aging mice by preventing atrial electrical and structural remodeling.
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MEDLINE
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En
Ano de publicação:
2024
Tipo de documento:
Article