Cardiac involvement in Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ): electrocardiographic, echocardiographic, and morphologic studies

Naoko Yugeta,Akinori Nakamura,Michiko R Wada,Yoko Fujii,Nobuyuki Urasawa,Yoshito Wakao,Akio Takahashi,Masao Nakura,Masayuki Tomohiro,Katsutoshi Yuasa,Noboru Machida,Madoka Yoshimura,Yoshiki Shimatsu,Shin'Ichi Takeda

doi:10.1186/1471-2261-6-47

Abstract

BackgroundCardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. The cardiac involvement is characterized by distinctive electrocardiographic abnormalities or dilated cardiomyopathy, but the pathogenesis has remained obscure. In research on DMD, Golden retriever-based muscular dystrophy (GRMD) has attracted much attention as an animal model because it resembles DMD, but GRMD is very difficult to maintain because of their severe phenotypes. We therefore established a line of dogs with Beagle-based canine X-linked muscular dystrophy in Japan (CXMDJ) and examined the cardiac involvement.MethodsThe cardiac phenotypes of eight CXMDJ and four normal male dogs 2 to 21 months of age were evaluated using electrocardiography, echocardiography, and histopathological examinations.ResultsIncreases in the heart rate and decreases in PQ interval compared to a normal littermate were detected in two littermate CXMDJ dogs at 15 months of age or older. Distinct deep Q-waves and increase in Q/R ratios in leads II, III, and aVF were detected by 6–7 months of age in all CXMDJ dogs. In the echocardiogram, one of eight of CXMDJ dogs showed a hyperechoic lesion in the left ventricular posterior wall at 5 months of age, but the rest had not by 6–7 months of age. The left ventricular function in the echocardiogram indicated no abnormality in all CXMDJ dogs by 6–7 months of age. Histopathology revealed myocardial fibrosis, especially in the left ventricular posterobasal wall, in three of eight CXMDJ dogs by 21 months of age.ConclusionCardiac involvement in CXMDJ dogs is milder and has slower progression than that described in GRMD dogs. The distinct deep Q-waves have been ascribed to myocardial fibrosis in the posterobasal region of the left ventricle, but our data showed that they precede the lesion on echocardiogram and histopathology. These findings imply that studies of CXMDJ may reveal not only another causative mechanism of the deep Q-waves but also more information on the pathogenesis in the dystrophin-deficient heart.

Highlights

Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator
None of the dogs in the present study showed clinical signs of heart failure, and no murmur was present on auscultation in any canine X-linked muscular dystrophy in Japan (CXMDJ) dog examined
We evaluated body and heart weight, the ratio of heart to body weight, and serum creatine kinase (CK) in eight CXMDJ and four normal male dogs aged 6–21 months just before euthanasia (Table 1)

Summary

Introduction

Cardiac mortality in Duchenne muscular dystrophy (DMD) has recently become important, because risk of respiratory failure has been reduced due to widespread use of the respirator. Duchenne muscular dystrophy (DMD) is a common and lethal genetic disease characterized by progressive muscle wasting. It is an X-linked recessive disorder caused by mutations in the dystrophin gene, which encodes a cytoskeletal protein, dystrophin [1]. Cardiac involvement, which occurs commonly in DMD patients, has increasingly become an important cause of death because recent clinical progress has reduced the risk of death due to respiratory failure [6,7]. Progressive involvement of the left ventricle leads to wall motion abnormality and results in dilated cardiomyopathy. One way to clarify these problems is to study suitable animal models

Methods

Results

Discussion

Conclusion