In this Physiology Shorts, Dr. Robert Lakin of York University in Toronto, Canada discusses their recent paper: The effects of daily dose of intense exercise on cardiac responses and atrial fibrillation Read more in The Journal of Physiology: The effects of daily dose of intense exercise on cardiac responses and atrial fibrillation. Renée A Gorman, Simona Yakobov, Nazari Polidovitch, Ryan Debi, Victoria C Sanfrancesco, David A Hood, Robert Lakin, Peter H Backx. 602(4), pp 569-596. Transcript: Hi. My name is Dr. Robert Lakin and I am a Research Associate at York University in Toronto, Canada. On behalf of myself, Renee Gorman, Peter Backx, and the other coauthors, I will be highlighting our most recent publication in The Journal of Physiology. What your group works on? Our group is focused on unravelling the mechanistic basis of atrial fibrillation (or AF), which is the most frequent sustained supraventricular arrhythmia in humans. While cardiovascular disease and aging are linked to an increased risk of AF, it is now clear that endurance athletes paradoxically have an AF risk similar to CVD, despite profoundly better ventricular function and cardiovascular health. The relationship between exercise and AF is complex, with studies demonstrating that intensity, duration, frequency and total dose can increase AF risk by as much as 10-fold. Indeed, previous studies have suggested that a J-shaped dose-response relationship exists between physical activity and cardiovascular health outcomes, wherein the benefits of low-to-moderate exercise to reduce AF prevalence yield to increased AF incidence in cohorts performing very high volumes of intense endurance exercise. Unfortunately, establishing an absolute risk of AF with exercise is difficult given the differences in study methodologies, with most conclusions relying on self-reporting to characterize exercise intensities and volumes. What your study investigated and found? Therefore, our current study was designed to assess quantitatively the impact of daily exercise dose on atrial remodeling and AF vulnerability using our mouse swim model (Figure 1 – 1:18-1:34). To achieve this, we quantified the exercise effort (work) of mice swimming for either 120, 180 or 240 minutes per day (split into two sessions) by measuring oxygen consumption rates and compared cardiac and skeletal muscle responses after all mice had achieved the same cumulative work during training. Despite physiological autonomic, ventricular and skeletal muscle adaptations characteristic of the athlete’s heart phenotype, (Figure 6 – 1:42-1:54) our findings demonstrated a novel interplay between electrical and structural changes in atria that appear to progressively predispose to AF inducibility as daily exercise dose is increased above 180 minutes per day, which was remarkedly consistent with thresholds linked to AF in humans. Mechanistically, our findings showed that beneficial elevations in vagal tone enhanced AF inducibility by reducing atrial refractoriness. Structurally (Figure 8 – 2:03-2:09), we found that collagen content and atrial size were increased in exercised mice, with a strong dependence on daily exercise amount. Importantly (Figure 11 – 2:10-2:22), tissue fibrosis and hypertrophy were invariably associated with increased atrial inflammation, with macrophage numbers significantly elevated in the atria (but not ventricles) of those mice with the greatest daily exercise dose. Significance of findings and its implications for future work (including any translational or clinical relevance) We believe our study is the first to quantitatively link daily exercise dose and AF risk in mice. Our findings support directly the previous human studies suggesting that CV health outcomes and AF vulnerability shows a J-shaped dependence on physical activity. The common atrial features of our exercised mice and persistent AF patients, including atrial fibrosis and inflammation, raise the possibility that the atria of endurance athletes may also undergo adverse changes, which might explain why endurance athletes, especially veteran athletes, have AF risks rivalling that seen in disease conditions despite the well-established benefits of moderate physical activity. Closing statement Thank you for taking the time to learn more about our study published in The Journal of Physiology. The full paper was published in Volume 602, issue 4.
