Differential myolysis of myocardium and skeletal muscle in hamsters with dilated cardiomyopathy - Beneficial protective effect of diltiazem

Background: Although dilated cardiomyopathic hamsters (TO-2) with mutation of the δ-sarcoglycan gene exhibit histological features of muscular dystrophy, it remains to be elucidated whether both myocardium and skeletal muscle are injured in a similar manner. Methods and Results: The progression of myolysis in both myocardium and skeletal muscle were assessed biochemically and pathologically in TO-2 and F1B control hamsters. Left ventricular (LV) function was assessed by echocardiography and cardiac catheterization. Both the plasma concentration of cardiac troponin T and the plasma activity of α-hydroxybutyrate dehydrogenase (HBD) peaked at 8 weeks of age, and thereafter reduced greatly in TO-2 hamsters. Activity of creatine kinase (CK) in TO-2 hamsters was significantly greater than in controls throughout the observation period. Pathological findings of both nuclear chain and central nuclei in skeletal muscles were observed in TO-2 hamsters throughout the observation period, suggesting regeneration. LV dysfunction was first evident at 8 weeks of age and deteriorated thereafter in TO-2 hamsters. Treatment of TO-2 hamsters with diltiazem from 5 to 8 weeks of age could avert the LV functional deterioration and the increment in α-HBD activity, but CK activity was unchanged. Conclusions: Despite myolysis in skeletal muscle occurring consistently throughout the observation period, cardiac myolysis occurred predominantly in the early phase. These initial cardiac events might involve coronary spasm and/or calcium overload in the myocardium.