Abstract 19168: Effect of Endurance Exercise on Transgenic Arrhythomeginc Right Ventricular Cardiomyopathy Mice
Introduction: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited disorder that causes sudden death and right ventricular heart failure in the young. Clinically, it has been suggested that competitive sports may accelerate ARVC pathogenesis in susceptible persons. The goal of this study was to investigate the cause and effect of exercise stress in the development of ARVC using a transgenic (Tg) mouse model with cardiac-restricted overexpression of human mutant R2834H desmoplakin (DSP).
Methods: DSPR2834H Tg (Tg-mut), non-transgenic human wild type DSP WT (Tg-wt) and control non-transgenic (Ntg) mice were divided into groups, sedentary and exercise. Mice in the exercise group were subjected to graded increase in intensity of exercise on a treadmill from the age of 4 weeks. Every 4 weeks, echocardiograms (echo) and ECGs (single lead) were recorded. Mice were dissected for tissue sampling and gross morphology.
Results: Initial echo data results are as shown in Table 1. When adjusted for age, number of days exercised, gender, interaction of genotype and exercise status, Tg-mut RV was bigger than Ntg mice (P=0.0005). Within the Tg-mut group, the RV diameter was not statistically significantly different between exercise and sedentary mice when adjusted for same variables. Heart weight/body weight ratio was higher in Tg-mut as compared to Ntg & lcub;sedentary (= 0.001) and exercise group (P = 0.0060} and Tg-wt. Tissue staining showed early development of fibrosis and fat in Tg-mut mice. The only significant ECG finding occurred in the exercise group: Tg-muthadincreased P wave amplitude and decreased R wave amplitude (P = 0.02 and P =0.001, respectively) compared to Ntg mice.
Conclusions: We report significant early histopathologic, and ECG changes with exercise in mutant DSPR2834H Tg mice compared to Ntg and Tg-wt mice.
- © 2012 by American Heart Association, Inc.