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。临床表现为进行性肌肉萎缩和无力。最近的医学进步降低了呼吸衰竭死亡的风险，延长了DMD患者的寿命。另一方面，心衰仍然是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动物模型和在模型中表征心肌病是了解DMD的病理生理学和开发心功能障碍治疗方案的有希望的方法。为此，本研究对日本CXMD （CXMD_J）犬心功能障碍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，但其表型尚未明确。观察CXMD_J犬的临床症状和心功能。为了了解CXMD_J的心脏改变过程，我们对CXMD_J犬的出生后心肌病发展进行了随访，直到21个月大。本研究结果为CXMD_J的心肌病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，在CXMD_J的早期发展过程中，也发现了ECQ自主神经障碍的临床表现和一种新的异常形式。此外，CXMD_J的心脏冲动传导改变，组织病理学检查显示浦肯野纤维变性。这些特征是新颖的，在以前的研究中没有报道过DMD，金毛肌肉萎缩症（GRMD）和CXMD。本研究表明CXMD_J是表征DMD病理，特别是临床重要心肌病发病机制的优良动物模型。

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.