Cardiac morphological and electrophysiological changes induced by sustained, high-intensity endurance training in large animal experimental models

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Despite the well-known benefits of regular exercise, there is a growing body of evidence suggesting that elite athletes who engage in intense training beyond a certain threshold are more susceptible to harmful ventricular cardiac arrhythmias, and in some cases, even sudden cardiac death, although the mechanisms behind this remain unclear. To gain a better understanding of cardiac remodelling in response to chronic vigorous exercise, this study explores the effects of such exercise on cardiac structure and electrophysiology in new rabbit and dog models of the athlete's heart. In the first experiments, rabbits and dogs were divided into sedentary (SED), exercised (EX) subjected to 16 weeks of chronic treadmill exercise, and a testosterone-treated group in dogs (DOP). In the second experiments, a more intense training protocol for dogs was introduced, and changes between trained (TRN) dogs and their sedentary (SED) counterparts were studied. Various tests, including echocardiography and electrocardiograms, were conducted, along with assessing proarrhythmic sensitivity and autonomic responses in conscious dogs. In vitro studies, such as electrophysiological measurements, immunocytochemistry, and histopathological analysis, were carried out after heart removal. Results showed that EX animals, both rabbits and dogs, displayed left ventricular enlargement and bradycardia, indicating an increased vagal tone. EX and DOP dogs showed a lower response to the parasympatholytic agent atropine and more pronounced QTc interval lengthening after dofetilide challenge compared to the SED group. No significant morphological or functional changes were observed in dogs treated with steroids. In conscious trained dogs, ECG recordings indicated bradycardia, prolonged QTc intervals, and increased QT interval variability, reflecting elevated repolarization dispersion. At the cellular level, prolonged action potential duration and reduced magnitude of the transient outward potassium current were observed in the left ventricular myocytes of trained dogs. Left ventricular fibrosis and increased HCN4 protein expression were also noted. Our findings provide in vivo, cellular electrophysiological, and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmias in the large animal model of chronic exercise. The sustained 4-month training regimen resulted in echocardiographic changes that are consistent with the morphology of the hearts of endurance-trained human athletes. These animal models hold promise for further investigations into the cardiovascular effects of competitive training.

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