Book of Abstracts - New Frontiers 2022

Abstracts of poster presentations

ENDURANCE TRAINING INDUCED CELLULAR ELECTROPHYSIOLOGICAL REMODELING IN NEWLY DEVELOPED ANIMAL ATHLETE’S HEART MODELS L. Topal 1 , A. Polyák 1,2 , N. Tóth 1 , Z. Kohajda 3 , S. Déri 1 , J. Prorok 1,3 , N. Nagy 1,3 , L. Virág 1,4 , N. Jost 1,3,4 , A. Farkas 5 , I. Baczkó 1,3 , A. Varró 1,3,4 1 University of Szeged Albert Szent- Györgyi Faculty of Medicine, Pharmacology and Pharmacotherapy, Szeged, Hungary; 2 University of Szeged Albert Szent- Györgyi Faculty of Medicine, Department of Pediatrics and Pediatric Health Center, Szeged, Hungary; 3 Eötvös Loránd Research Network, ELKH -SZTE Research Group of Cardiovascular Pharmacology, Szeged, Hungary; 4 University of Szeged, Department of Pharmacology and Pharmacotherapy, Interdisciplinary Excellence Centre, Szeged, Hungary; 5 University of Szeged Albert Szent Györgyi Faculty of Medicine, Department of Internal Medicine, Cardiology, Szeged, Hungary Introduction: The benefits of regular training for a healthy life are undoubted. However, based on accumulating evidence, long-term heavy training beyond an optimal dose may also have cardiac electrophysiological adverse effects under certain circumstances. Structural and functional changes, including repolarization abnormalities because of vigorous training, may underlie the development of malignant arrhythmias. Aims: To develop animal models with significant translational value for human athlete’s heart and to investigate potential cellular electrophysiological causes of cardiac arrhythmias because of long-term heavy endurance training in in vitro studies. Methods: Twenty-four dogs and twenty- six guinea pigs were randomized into sedentary (’Sed’) and exercised (’Ex’) groups ( n=12-12; n=13-13). The latter groups underwent an intensive several week-long endurance training program on special treadmill system. Characteristics of athlete’s heart were validated by ECG and echocardiography. After heart removal, the degree of interstitial fibrosis was quantified in semi-quantitative histopathological study and left ventricular myocytes were enzymatically isolated via retrograde perfusion. Transmembrane ionic currents were recorded using whole-cell configuration of patch clamp technique and action potential duration (APD) was measured by perforated patch-clamp technique. Immunocytochemistry measurements were performed to determine the density of transmembrane ion channel subunits. Results: Based on the ECG and ECHO results, the vigorous training program resulted in significant cardiac adaptation in both species. In addition, it caused mild ventricular fibrosis. The repolarization reflected as 90 percent of APD (APD90) was significantly lengthened in the left ventricular myocytes isolated from the ‘Ex’ dogs compared to the ‘Sed’ group (472.8±29.6 ms; n=29 vs. 369.3±31.4 ms; n=24 p=0.023), however, no statistically significant difference was detected between the ‘Sed’ and ‘Ex’ groups in case of guinea pigs. The amplitude of the transient outward potassium current (Ito), which is not expressed in the guinea pig heart, was significantly smaller in the ‘Ex’ dogs (‘Ex’ vs. ‘Sed’ 7.6±0.6 pA/pF, n=54 vs. 10.2±1.0 pA/pF, n=42, p<0.05). Under the currently used protocols, no differences were detected in the magnitude of other ionic currents between the groups. The HCN4 protein expression was significantly higher in isolated ventricular myocytes obtained from ’Ex’ dogs. Conclusion: Besides long-term heavy training induced in vivo observed changes, cellular electrophysiological remodeling, as well as, decreased Ito magnitude, therefore, prolonged action potential duration, and increased expression profile of HCN4 protein, moreover, enhanced level of fibrosis together may ay lead to increased susceptibility of life-threatening arrhythmias in a vulnerable period. Further studies are warranted to clarify this hypothesis in more detail.

Keywords: athlete’s heart, patch -clamp, Ito-current, electrophysiology

Funding:Supported by NKFIH grants (K-19992, K- 135464, GINOP-2.3.2-15-2016-00047).

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