Differential Myolysis of Myocardium and Skeletal Muscle in Hamsters With Dilated Cardiomyopathy

Beneficial Protective Effect of Diltiazem

Abstract

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. (Circ J 2006; 70: 1497 - 1502)