Cardiac electrophysiological remodeling associated with enhanced arrhythmia susceptibility in a canine model of elite exercise.
Alexandra PolyákLeila TopalNoémi Zombori-TóthNoémi TóthJános ProrokZsófia KohajdaSzilvia DériVivien Demeter-HaludkaBálint ErőssViktória VengloveczGergely ÁgostonZoltán HustiPéter GazdagJozefina SzlovákTamás Árpádffy-LovasMuhammad NaveedAnnamária SarusiNorbert JostLászló VirágNorbert NagyIstvan BaczkoAttila S FarkasAndrás VarróPublished in: eLife (2023)
The health benefits of regular physical exercise are well known. Even so, there is increasing evidence that the exercise regimes of elite athletes can evoke cardiac arrhythmias including ventricular fibrillation and even sudden cardiac death (SCD). The mechanism of exercise-induced arrhythmia and SCD is poorly understood. Here, we show that chronic training in a canine model (12 sedentary and 12 trained dogs) that mimics the regime of elite athletes induces electrophysiological remodeling (measured by ECG, patch-clamp, and immunocytochemical techniques) resulting in increases of both the trigger and the substrate for ventricular arrhythmias. Thus, 4 months sustained training lengthened ventricular repolarization (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, n=29 vs. 25), decreased transient outward potassium current (6.4±0.5 pA/pF vs. 8.8±0.9 pA/pF at 50 mV, n=54 vs. 42), and increased the short-term variability of repolarization (29.5±3.8 ms vs. 17.5±4.0 ms, n=27 vs. 18). Left ventricular fibrosis and HCN4 protein expression were also enhanced. These changes were associated with enhanced ectopic activity (number of escape beats from 0/hr to 29.7±20.3/hr) in vivo and arrhythmia susceptibility (elicited ventricular fibrillation: 3 of 10 sedentary dogs vs. 6 of 10 trained dogs). Our findings provide in vivo, cellular electrophysiological and molecular biological evidence for the enhanced susceptibility to ventricular arrhythmia in an experimental large animal model of endurance training.
Keyphrases
- left ventricular
- catheter ablation
- mass spectrometry
- multiple sclerosis
- ms ms
- heart failure
- resistance training
- physical activity
- left atrial
- body composition
- atrial fibrillation
- hypertrophic cardiomyopathy
- acute myocardial infarction
- high intensity
- cardiac resynchronization therapy
- healthcare
- mitral valve
- aortic stenosis
- mental health
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- skeletal muscle
- aortic valve
- health information
- congenital heart disease
- blood pressure
- transcatheter aortic valve replacement
- risk assessment
- heart rate
- drug induced
- human health
- blood brain barrier
- single molecule
- percutaneous coronary intervention
- subarachnoid hemorrhage