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.
Keywords: ACE inhibitor; Aging; Atrial fibrillation; Fibrosis; Frailty; Ion channels.
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