In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy

Hdl Handle:
http://hdl.handle.net/10675.2/691
Title:
In vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophy
Authors:
Stuckey, Daniel J.; Carr, Carolyn A.; Camelliti, Patrizia; Tyler, Damian J.; Davies, Kay E. ( 0000-0001-8807-8520 ) ; Clarke, Kieran
Abstract:
Aims: The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice.; Methods and Results: Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy.; Conclusions: MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.
Editors:
McNeil, Paul L.
Citation:
PLoS One. 2012 Jan 3; 7(1):e28569
Issue Date:
3-Jan-2012
URI:
http://hdl.handle.net/10675.2/691
DOI:
10.1371/journal.pone.0028569
PubMed ID:
22235247
PubMed Central ID:
PMC3250389
Type:
Article
ISSN:
1932-6203
Appears in Collections:
Department of Cellular Biology and Anatomy Faculty Papers

Full metadata record

DC FieldValue Language
dc.contributor.authorStuckey, Daniel J.en_US
dc.contributor.authorCarr, Carolyn A.en_US
dc.contributor.authorCamelliti, Patriziaen_US
dc.contributor.authorTyler, Damian J.en_US
dc.contributor.authorDavies, Kay E.en_US
dc.contributor.authorClarke, Kieranen_US
dc.contributor.editorMcNeil, Paul L.-
dc.date.accessioned2012-10-26T16:29:34Z-
dc.date.available2012-10-26T16:29:34Z-
dc.date.issued2012-01-3en_US
dc.identifier.citationPLoS One. 2012 Jan 3; 7(1):e28569en_US
dc.identifier.issn1932-6203en_US
dc.identifier.pmid22235247en_US
dc.identifier.doi10.1371/journal.pone.0028569en_US
dc.identifier.urihttp://hdl.handle.net/10675.2/691-
dc.description.abstractAims: The mdx mouse has proven to be useful in understanding the cardiomyopathy that frequently occurs in muscular dystrophy patients. Here we employed a comprehensive array of clinically relevant in vivo MRI techniques to identify early markers of cardiac dysfunction and follow disease progression in the hearts of mdx mice.en_US
dc.description.abstractMethods and Results: Serial measurements of cardiac morphology and function were made in the same group of mdx mice and controls (housed in a non-SPF facility) using MRI at 1, 3, 6, 9 and 12 months after birth. Left ventricular (LV) and right ventricular (RV) systolic and diastolic function, response to dobutamine stress and myocardial fibrosis were assessed. RV dysfunction preceded LV dysfunction, with RV end systolic volumes increased and RV ejection fractions reduced at 3 months of age. LV ejection fractions were reduced at 12 months, compared with controls. An abnormal response to dobutamine stress was identified in the RV of mdx mice as early as 1 month. Late-gadolinium-enhanced MRI identified increased levels of myocardial fibrosis in 6, 9 and 12-month-old mdx mice, the extent of fibrosis correlating with the degree of cardiac remodeling and hypertrophy.en_US
dc.description.abstractConclusions: MRI could identify cardiac abnormalities in the RV of mdx mice as young as 1 month, and detected myocardial fibrosis at 6 months. We believe these to be the earliest MRI measurements of cardiac function reported for any mice, and the first use of late-gadolinium-enhancement in a mouse model of congenital cardiomyopathy. These techniques offer a sensitive and clinically relevant in vivo method for assessment of cardiomyopathy caused by muscular dystrophy and other diseases.en_US
dc.rightsStuckey et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.en_US
dc.subjectResearch Articleen_US
dc.subjectBiologyen_US
dc.subjectAnatomy and Physiologyen_US
dc.subjectMedicineen_US
dc.subjectCardiovascularen_US
dc.subject.meshAnimalsen_US
dc.subject.meshDisease Models, Animalen_US
dc.subject.meshDisease Progressionen_US
dc.subject.meshDobutamineen_US
dc.subject.meshFibrosisen_US
dc.subject.meshGadoliniumen_US
dc.subject.meshHearten_US
dc.subject.meshMagnetic Resonance Imagingen_US
dc.subject.meshMaleen_US
dc.subject.meshMiceen_US
dc.subject.meshMice, Inbred mdxen_US
dc.subject.meshMuscular Dystrophiesen_US
dc.subject.meshMyocardiumen_US
dc.subject.meshStress, Physiologicalen_US
dc.subject.meshTime Factorsen_US
dc.subject.meshVentricular Dysfunction, Leften_US
dc.subject.meshVentricular Dysfunction, Righten_US
dc.titleIn vivo MRI Characterization of Progressive Cardiac Dysfunction in the mdx Mouse Model of Muscular Dystrophyen_US
dc.typeArticleen_US
dc.identifier.pmcidPMC3250389en_US
dc.contributor.corporatenameDepartment of Cellular Biology and Anatomy-
dc.contributor.corporatenameCollege of Graduate Studies-

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