Level and clinical picture of myocardial failure in Duchenne type muscular dystrophy

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Duchenne muscular dystrophy (DMD) is a hereditary disorder in human characterized by progressive muscular degeneration and necrosis. Clinically, it is marked by progressive muscular atrophy and weakness.Recent advancements in medicine have reduced the risk of death from respiratory failure and prolonged the life span of DMD patients. On the other hand, cardiac failure is still the primary cause of death in DMD, as it is treated only conservatively. As such, development of a better animal model of DMD and characterization of cardiomyopathy in the model are promising approaches for pathophysiological understanding and development of therapeutic options for cardiac dysfunction in DMD. To this end, the clinical and pathological presentations of cardiac dysfunction were characterized in dogs with Japanese CXMD (CXMD_J) in this study. Although CXMD_J shares the same genetic background with DMD, its phenotype is ill defined. Clinical symptoms and cardiac function, was examined in dogs with CXMD_J. To understand the course of cardiac alteration in CXMD_J, postnatal development of cardiomyopathy was followed in dogs with CXMD_J until 21 months of age. The results of this study provided a clue to the pathogenesis of cardiomyopathy in CXMD_J and demonstrated the usefulness of CXMD_J as an animal model of DMD. The present study confirmed that clinical presentations and a novel form of abnormality in ECQ autonomic disturbance were also found during early development of CXMD_J. Further, cardiac impulse conduction is altered in CXMD_J, and histopathological examination revealed degeneration of Purkinje fibers. These characteristics are novel and have not been reported in previous studies of DMD, Golden Retriever muscular dystrophy (GRMD) and CXMD. The study demonstrated that CXMD_J is an excellent animal model for characterization of DMD pathology, especially for pathogenesis of clinically important cardiomyopathy.