Abstract

Aims: Increasing age is the most important risk factor for atrial fibrillation (AF). Very high doses of exercise training might increase AF risk, while moderate levels seem to be protective. This study aimed to examine the effects of age on vulnerability to AF and whether long-term aerobic interval training (AIT) could modify these effects.Methods: Nine months old, male Sprague-Dawley rats were randomized to AIT for 16 weeks (old-ex) or to a sedentary control group (old-sed), and compared to young sedentary males (young-sed). After the intervention, animals underwent echocardiography, testing of exercise capacity (VO2max), and electrophysiology with AF induction before ex vivo electrophysiology. Fibrosis quantification, immunohistochemistry and western blotting of atrial tissue were performed.Results: Sustained AF was induced in vivo in 4 of 11 old-sed animals, but none of the old-ex or young-sed rats (p = 0.006). VO2max was lower in old-sed, while old-ex had comparable results to young-sed. Fibrosis was increased in old-sed (p = 0.006), with similar results in old-ex. There was a significantly slower atrial conduction in old-sed (p = 0.038), with an increase in old-ex (p = 0.027). Action potential duration was unaltered in old-sed, but prolonged in old-ex (p = 0.036). There were no differences in amount of atrial connexin 43 between groups, but a lateralization in atrial cardiomyocytes of old-sed, with similar findings in old-ex.Conclusion: AF vulnerability was higher in old-sed animals, associated with increased atrial fibrosis, lateralization of connexin-43, and reduced atrial conduction velocity. AIT reduced the age-associated susceptibility to AF, possibly through increased conduction velocity and prolongation of action potentials.

Highlights

  • Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, with an estimated prevalence of 2–3% in the adult population

  • The present study demonstrates that the increased AF susceptibility with aging was associated with atrial fibrosis, reduced atrial conduction velocity (CV) and lateralization of cx-43

  • Aerobic interval training (AIT) protected against this age-dependent AF, and was associated with increased atrial CV, prolongation of the action potential (AP) and reduced AP alternans at higher heart rates, with no detected effects on the increased atrial fibrosis and cx-43 lateralization

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Summary

Introduction

Atrial fibrillation (AF) is the most common sustained arrhythmia in humans, with an estimated prevalence of 2–3% in the adult population. It is associated with increased morbidity and mortality, mainly due to embolic stroke and associated comorbidities (Kirchhof et al, 2016). Focal ectopic firing, caused by abnormal Ca2+ handling and changes in autonomic nerve activity and response, is the common trigger of AF episodes. This will usually not cause sustained AF in the healthy atria. The most common electrophysiological mechanisms maintaining AF are re-entry and rotor activity, and less commonly rapid ectopic firing (Andrade et al, 2014; Heijman et al, 2014)

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