Functional and morphological elucidation of the early pathophysiology of muscular dystrophy cardiomyopathy by optical mapping of pig perfused hearts

2023 Fiscal Year Final Research Report

• Project/Area Number: 22K20620
• Research Category: Grant-in-Aid for Research Activity Start-up
• Allocation Type: Multi-year Fund
• Review Section: 0605:Veterinary medical science, animal science, and related fields
• Research Institution: Azabu University
• Principal Investigator: Shiga Takanori 麻布大学, 獣医学部, 助教 (20963482)
• Project Period (FY): 2022-08-31 – 2024-03-31
• Keywords: 筋ジストロフィー / 心筋症 / 豚モデル / ランゲンドルフ灌流心 / 光学マッピング解析

Outline of Final Research Achievements

We aimed to elucidate the early pathogenesis of cardiomyopathy caused by dystrophin deficiency in both function and morphology by ex vivo analysis using excised hearts from a Becker muscular dystrophy (BMD) porcine cardiomyopathy model. The retained sows of this porcine model were mated three times and electrocardiography was performed in vivo under isoflurane inhalation anesthesia. In addition, hearts were excised and perfused hearts were created using the Langendorff method, ECG recordings, arrhythmia induction, and optical mapping analysis were performed. We were able to reproduce the arrhythmogenesis induced by isoflurane anesthesia in both the live and excised perfused hearts, confirming the usefulness of the BMD porcine cardiomyopathy model. Furthermore, abnormal excitation propagation (functional abnormalities) of the myocardium during arrhythmias in BMD porcine cardiomyopathy was revealed.

Free Research Field

獣医病理学

Academic Significance and Societal Importance of the Research Achievements

ヒトBMD患者では骨格筋機能や呼吸機能が保たれた状態でも、重症心筋症を発症することから、約半数の死因は心筋症である。また、無症状のBMD患者が激しい運動や麻酔処置を契機に不整脈を発症し、突然死する事例も報告されているが、現在の医療では心筋症初期段階での突然死を予防できない。本研究では、豚のBMD心筋症の初期病態における不整脈時の心筋異常興奮伝播(機能異常)を明らかにした。今後は灌流後の心臓の組織病変を形態学的に精査する。不整脈の病理発生機序を解明することができれば、ヒトBMD心筋症の治療研究の重要な起点となり、不整脈の病理診断においてもブレイクスルーとなることが期待される。