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

杜氏肌营养不良症（DMD）是一种以进行性肌肉变性和坏死为特征的遗传性疾病。临床上，它的特征是肌肉萎缩和虚弱。最近的医学进步降低了呼吸衰竭的死亡风险，延长了DMD患者的寿命。另一方面，心力衰竭仍然是DMD的主要死亡原因，因为它只能保守治疗。因此，开发更好的DMD动物模型和表征模型中的心肌病是有前途的方法，用于病理生理学理解和开发DMD心功能不全的治疗方案。为此，在本研究中，对日本CXMD（CXMD_J）犬的心功能不全的临床和病理表现进行了表征。虽然CXMD_J与DMD具有相同的遗传背景，但其表型不明确。对CXMD_J犬的临床症状和心功能进行了检查。为了了解CXMD_J犬心脏改变的过程，对CXMD_J犬的心肌病出生后发展进行了随访，直至21月龄。本研究结果为CXMD_J心肌病的发病机制提供了线索，并证明了CXMD_J作为DMD动物模型的有效性。本研究证实，临床表现和一种新的形式的异常ECQ自主神经紊乱也发现在CXMD_J的早期发展。此外，心脏冲动传导改变CXMD_J，和组织病理学检查显示浦肯野纤维变性。这些特征是新的，在以前的DMD、金毛猎犬肌营养不良症（GRMD）和CXMD的研究中没有报道。CXMD_J是研究DMD病理学，特别是临床重要心肌病发病机制的理想动物模型。

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.