Abstract 12224: Ventricular Arrhythmogenic Remodeling in a Rat Model of Intense Endurance Training
Background: High intensity exercise has been suggested to increase right ventricular (RV) arrhythmias and possibly contribute to sudden death. Here, we studied the relationship between intense exercise and ventricular arrhythmias and their mechanisms in a rat model.
Methods: Rats were subjected to daily 1 hour treadmill training (Ex, n=16) or parallel sedentary housing (n=12). After 16 weeks, ventricular arrhythmia inducibility was assessed (EPS) and echocardiography was performed. mRNA expression and protein expression of fibrosis markers (TGF-β1, fibronectin, MMP2, TIMP1, procollagen/collagen-I and -III) were quantified in ventricular samples. Myocardial fibrosis was confirmed by tissue hydroxyproline (HP) assay and myofibroblast differentiation evaluated with α-SMA detection. Fibrosis markers were also determined after 2 or 4 weeks detraining (n=6 each).
Results: Ex rats were more frequently arrhythmia-inducible than sedentary rats (42% vs 6%, p=0.05). Echocardiography showed LV hypertrophy and slight systolic and diastolic LV dysfunction in the Ex group, whereas RV results were comparable between groups. In the RV from rats subjected to exercise, increased mRNA and protein expression of fibrosis markers were found (figure). Accordingly, increased HP content was found in the RV from Ex group (2.3±0.1 vs 1.2±0.1 μg HP/mg dried tissue). Increased RV myofibroblast content was suggested by increased α-SMA immunofluorescence (figure) and immunoblot intensity. Fibrosis markers regressed after deconditioning. The LV showed no differences between Ex and sedentary in any fibrosis markers.
Conclusions: In this rat model, intense endurance training increased ventricular arrhythmia vulnerability, produced LV hypertrophy/dysfunction and caused reversible RV fibrosis, which could underlie the arrhythmogenic substrate. Our results contribute to understanding potential ventricular arrhythmia mechanisms in otherwise healthy athlete's hearts.
- © 2010 by American Heart Association, Inc.