Cardiac electrophysiological characteristics of the mdx^5cv mouse model of Duchenne muscular dystrophy

Background: Duchenne muscular dystrophy (DMD) is a progressive muscle disease caused by mutations in the dystrophin gene. Cardiomyopathy, conduction abnormalities, and ventricular arrhythmias are significant complications of this disease. The mdx^5cv mouse carries a dystrophin mutation and demonstrates a more severe phenotype than the classic mdx mouse. Methods: Comprehensive electrophysiological phenotyping was performed in adult mdx ^5cv and wildtype mice, including electrocardiography (ECG), implantable Holter monitoring, intracardiac electrophysiological testing, echocardiography, and exercise treadmill testing. Results: ECG performed in mdx^5cv mice revealed significantly shorter PR intervals and prominent R waves in surface lead V1. During electrophysiological testing, mdx ^5cv mice exhibited longer ventricle effective refractory periods and mildly increased ventricular tachycardia inducibility. There was no evidence for cardiomyopathy or ventricular dysfunction on echocardiography. Histopathology showed no increased myocardial fibrosis. Exercise endurance was lower in mdx^5cv mice without arrhythmias or other cardiac abnormalities. Conclusion: Taken together at the age range examined, mdx^5cv mice exhibit discrete cardiac electrophysiological dysfunction but display no evidence of structural or contractile abnormalities. Thus, the mdx^5cv mouse recapitulates some of the electrophysiological, but not hemodynamic cardiac defects present in human DMD. In certain settings, the mdx^5cv mouse may be an appropriate subject for studying electrical pathophysiology and therapy of the cardiac complications of DMD.