P18 Beta-blocker/ACE-inhibitor combination treatment in mdx mice

Abstract

Cardiomyopathy is the major cause of mortality in Duchenne Muscular Dystrophy (DMD) patients. We wished to explore the advantages of early treatment with a combination of b-blocker and ACE-inhibitor, over treatment with each drug in isolation. We were particularly interested to learn if these treatments would have an impact on the pronounced right ventricular pathology seen in mdx. Male mdx mice were treated with metoprolol and/or captopril for 8 weeks from 16 weeks of age (prior to development of overt cardiomyopathic features) and assessed by MRI and cardiac conductance catheter at 24 weeks of age. Combination treatment produced a reduction in left ventricular mass and increased ejection fraction. However, 24 week old mdx mouse hearts are not hypertrophic and have a normal ejection fraction at baseline. Metoprolol and combination treatment both resulted in a normalization of left ventricular contractility (as measured by ESPVR) however none of the treatments were effective in preventing right ventricular dysfunction or global cardiac histopathology. Overall, there appeared to be little added benefit of administering captopril with metoprolol in the mouse model of DMD.