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

杜氏型肌营养不良症心肌衰竭程度及临床表现

• 批准号: 15580293
• 负责人: WAKAO Yosito
• 金额: $ 2.11万
• 依托单位: Azabu University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2004
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15580293/
• 关键词: Duchenne type muscular dystrophy; Cardiomyopathy; Canine; Abnormal electrocardiogram; 心電図異常

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.

Duchenne肌营养不良症是一种以进行性肌肉变性和坏死为特征的遗传性疾病。临床上以进行性肌肉萎缩和虚弱为特征。最近的医学进步降低了呼吸衰竭的死亡风险，延长了DMD患者的生命。另一方面，心力衰竭仍然是DMD死亡的主要原因，因为它只被保守治疗。因此，发展一种更好的DMD动物模型，并在该模型中确定心肌病的特征，是了解DMD心脏功能障碍的病理生理学和开发治疗方案的有希望的途径。为此，本研究对日本CXMD(CXMD_J)犬心功能不全的临床和病理表现进行了研究。虽然CXMD_J与DMD具有相同的遗传背景，但其表型尚不明确。对CXMD_J犬的临床症状和心功能进行检测。为了解CXMD_J犬心脏改变的过程，对CXMD_J犬出生后心肌病的发展进行跟踪观察，直至21个月龄。本研究结果为探讨CXMD_J心肌病的发病机制提供了线索，证明了CXMD_J作为DMD动物模型的可行性。本研究证实，在CXMD_J的早期发展过程中，还发现了临床表现和一种新的ECQ自主神经紊乱形式，此外，CXMD_J的心脏冲动传导也发生了改变，组织病理学检查显示浦肯野纤维变性。这些特征是新的，在以前对DMD、金猎犬肌营养不良症(GRMD)和CXMD的研究中没有报道。研究表明，CXMD_J是研究DMD病理，尤其是研究临床重要心肌病发病机制的良好动物模型。