SCIENTIFIC JOURNAL of the Hungarian Society of Cardiology

Ventricular myocardial remodeling associated with increased arrhythmia sensitivity in a large animal athlete’s heart model

█ Original article

DOI: 10.26430/CHUNGARICA.2023.53.5.436

Authors:
Pintér Jenő Antal1, Polyák Alexandra2, Varró András3,4, Farkas S Attila1, Baczkó István3, Topal Leila3
1Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Kardiológia, Szeged
2Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Belgyógyászati Klinika, Szeged
3Szegedi Tudományegyetem, Szent-Györgyi Albert Orvostudományi Kar, Farmakológiai és Farmakoterápiai Intézet, Szeged
4HUN-REN-SZTE Keringésfarmakológiai kutatócsoport, Szeged

Summary

Several recent studies have highlighted that high-intensity training may predispose to cardiac arrhythmias and, in severe cases, sudden cardiac death, but the underlying electrophysiological mechanisms are poorly understood. Our study investigated cardiac remodeling and susceptibility to ventricular arrhythmias induced by sustained endurance training in a canine model of elite exercise. Beagle dogs were randomized to a “control” or a “trained” group (n=12/group). The trained group participated in a 4-month intensive training program. Cardiac remodeling and arrhythmia susceptibility were investigated using various in vivo and in vitro methods (elect­rocardiography, echocardiography, ventricular burst stimulation, patch-clamp, immunocytochemistry and histopathological studies). The training program led to increased septal wall thickness (8.13±0.2 mm vs. 7.4±0.2 mm; p<0.05), left ventricular end-diastolic dia­meter (32.0±0.7 mm vs. 30.4±0.7 mm; p<0.05), and left ventricular mass index (125.8±4.3 g/m2 vs. 97.7±6.4 g/m2; p<0.05). In trained animals, prolonged ventricular repolarization was detected under in vivo and in vitro conditions (QTc: 237.1±3.4 ms vs. 213.6±2.8 ms, n=12; APD90: 472.8±29.6 ms vs. 370.1±32.7 ms; p<0.05), accompanied with increased short-term variability of repolarization. The amplitude of the transient outward K+-current in left ventricular myocytes isolated from the hearts of the trained animals was reduced (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF, at 50 mV; p<0.05), additionally, the degree of left ventricular fibrosis and HCN4 protein expression were increased. Additionally, there was a notable increase in ectopic activity in trained dogs. The exercise program resulted in clear cardiac structural and electrophysiological alterations. Our study suggests that increased repolarization dispersion, elevated fibrosis, and overexpression of HCN4 indicate increased susceptibility of the model to arrhythmias.

ISSUE: CARDIOLOGIA HUNGARICA | 2023 | VOLUME 53, ISSUE 5

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