title: Absence of Cardiac Benefit with Early Combination ACE Inhibitor and Beta Blocker Treatment in mdx Mice.
abstract: Most patients with Duchenne muscular dystrophy (DMD) will develop cardiomyopathy; however, the evidence for prophylactic treatment of children with cardiac medications is limited. We have used the mdx mouse model of DMD to assess if early combination treatment with beta blocker (BB) and ACE inhibitor (AI) is superior to single treatment with either one of these drugs. Mice were assessed with cardiac MRI (ventricular structure and function, in vivo calcium influx (manganese-enhanced MRI)), pressure-volume loops, and histopathology. Combination treatment did not show benefits over treatment with AI or BB alone. Indeed, some beneficial aspects of BB and AI were lost when used in combination. None of the treatments impacted RV function. Combination treatment had no significant effect on sarcolemmal damage or histopathology. The study suggests that combined BB and AI may not confer an advantage at an early stage in DMD cardiomyopathy. However, limitations of the mdx model should be considered.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne, NE1 3BZ, UK.
authors.forename: Alison
authors.initials: A
authors.lastname: Blain
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Greally
authors.forename: Steven H
authors.initials: SH
authors.lastname: Laval
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.forename: Guy A
authors.initials: GA
authors.lastname: MacGowan
authors.forename: Volker W
authors.initials: VW
authors.lastname: Straub
mesh_terms: D000319:Adrenergic beta-Antagonists / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology*; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002216:Captopril / Q000494:pharmacology*; D006328:Cardiac Catheterization; D009202:Cardiomyopathies / Q000209:etiology / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination; D008279:Magnetic Resonance Imaging; D008297:Male; D008790:Metoprolol / Q000494:pharmacology*; D018101:Mice, Inbred mdx; D020388:Muscular Dystrophy, Duchenne / Q000150:complications / Q000188:drug therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D013318:Stroke Volume / Q000187:drug effects; D013997:Time Factors; D016277:Ventricular Function, Left / Q000187:drug effects; D016278:Ventricular Function, Right; D017725:Ventricular Pressure / Q000187:drug effects
chemical_list: D000319:Adrenergic beta-Antagonists; D000806:Angiotensin-Converting Enzyme Inhibitors; D002216:Captopril; D008790:Metoprolol; D002118:Calcium