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.


CONCLUSIONS
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.
Branco
Dorothy M
DM
Department of Cardiology, Children's Hospital Boston, Boston, MA 02115, USA.
Wolf
Cordula M
CM
Sherwood
Megan
M
Hammer
Peter E
PE
Kang
Peter B
PB
Berul
Charles I
CI
D000818:Animals; D001145:Arrhythmias, Cardiac / Q000175:diagnosis / Q000209:etiology* / Q000503:physiopathology*; D004195:Disease Models, Animal; D004562:Electrocardiography; D005260:Female; D006329:Heart Conduction System / Q000503:physiopathology*; D006339:Heart Rate; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000150:complications* / Q000175:diagnosis / Q000503:physiopathology*