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Absence of Cardiac Benefit with Early Combination ACE Inhibitor and Beta Blocker Treatment in mdx Mice

Lookup NU author(s): Dr Alison Blain, Liz Greally, Dr Steven Laval, Professor Andrew BlamireORCiD, Dr Guy MacGowanORCiD, Professor Volker StraubORCiD

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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.


Publication metadata

Author(s): Blain A, Greally E, Laval SH, Blamire AM, MacGowan GA, Straub VW

Publication type: Article

Publication status: Published

Journal: Journal of Cardiovascular Translational Research

Year: 2015

Volume: 8

Issue: 3

Pages: 198-207

Print publication date: 01/04/2015

Online publication date: 21/04/2015

Acceptance date: 06/04/2015

ISSN (print): 1937-5387

ISSN (electronic): 1937-5395

Publisher: Springer

URL: http://dx.doi.org/10.1007/s12265-015-9623-7

DOI: 10.1007/s12265-015-9623-7


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Funding

Funder referenceFunder name
17853AFM
2585Heart Research UK
FS/11/89/29162British Heart Foundation Clinical Leave Research Fellowship (GMcG)

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