title: Assessment of ventricular function in mouse models of muscular dystrophy: a comparison of MRI with conductance catheter.
abstract: Outcomes of clinical trials depend on the quality of preceding preclinical research, yet functional assays and outcome measures for mouse models of disease are often poorly standardized or inappropriate. Muscular dystrophies are associated with cardiomyopathy so preclinical research requires reliable measures of cardiac function in animal models of the disease. MRI and conductance catheter were compared as preclinical tools to detect cardiomyopathy in two mouse models of muscular dystrophy. Sgcd-/-, mdx and C57Bl10 mice (n = 7/group) were assessed by catheter following MRI at an early stage of cardiomyopathy. Volumetric measurements were higher from MRI compared to catheter. In particular, by catheter, the measurement of end-systolic volume (and its related measures) was disproportionately lower in dystrophic mice compared to controls. This was related to greater calculated parallel conductance in dystrophic mice. Catheter highlighted differences in pressure generation between the two models while MRI detected differences in left ventricular hypertrophy and right ventricular function. Although MRI and conductance catheter provide unique but complimentary information regarding the nature of cardiomyopathy in dystrophic mice, we present the possibility that pathology itself may affect the accuracy of the catheter technique and that particular caution must be taken when interpreting catheter volume data in dystrophic mice.
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK.
authors.forename: Alison M
authors.initials: AM
authors.lastname: Blain
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK.
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Greally
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK.
authors.forename: Steven H
authors.initials: SH
authors.lastname: Laval
authors.affiliation: Institute of Cellular Medicine & Newcastle Magnetic Resonance Centre, Campus for Ageing and Vitality, Newcastle University, Newcastle Upon Tyne NE4 5PL, UK.
authors.forename: Andrew M
authors.initials: AM
authors.lastname: Blamire
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK; Department of Cardiology, Freeman Hospital, Newcastle Upon Tyne, UK.
authors.forename: Guy A
authors.initials: GA
authors.lastname: MacGowan
authors.affiliation: Institute of Genetic Medicine, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE1 3BZ, UK. Electronic address: Volker.straub@ncl.ac.uk.
authors.forename: Volker W
authors.initials: VW
authors.lastname: Straub
mesh_terms: D000818:Animals; D006328:Cardiac Catheterization; D062906:Cardiac Catheters; D002306:Cardiac Volume; D009202:Cardiomyopathies / Q000175:diagnosis* / Q000209:etiology*; D004195:Disease Models, Animal; D019028:Magnetic Resonance Imaging, Cine; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018101:Mice, Inbred mdx; D018345:Mice, Knockout; D009136:Muscular Dystrophies / Q000150:complications*; D049031:Sarcoglycans / Q000235:genetics; D018754:Ventricular Dysfunction / Q000175:diagnosis
chemical_list: D049031:Sarcoglycans
keywords: Cardiac MRI; Cardiac conductance catheter; Mdx mouse; Outcome measures; Preclinical research; Sgcd−/− mouse; cardiomyopathy