Differential myolysis of myocardium and skeletal muscle in hamsters with dilated cardiomyopathy: beneficial protective effect of diltiazem

Circ J. 2006 Nov;70(11):1497-502. doi: 10.1253/circj.70.1497.

Abstract

Background: Although dilated cardiomyopathic hamsters (TO-2) with mutation of the delta-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 alpha-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 alpha-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.

MeSH terms

  • Animals
  • Calcium Channel Blockers / pharmacology
  • Calcium Channel Blockers / therapeutic use*
  • Cardiomyopathy, Dilated / genetics
  • Cardiomyopathy, Dilated / metabolism
  • Cardiomyopathy, Dilated / pathology*
  • Creatine Kinase / blood
  • Cricetinae
  • Diltiazem / pharmacology
  • Diltiazem / therapeutic use*
  • Echoencephalography
  • Gene Expression Regulation / genetics
  • Gene Expression Regulation / physiology
  • Heart / drug effects
  • Heart / physiopathology
  • Hydroxybutyrate Dehydrogenase / blood
  • Male
  • Muscle, Skeletal / drug effects
  • Muscle, Skeletal / metabolism
  • Muscle, Skeletal / pathology*
  • Muscle, Skeletal / physiopathology
  • Mutation
  • Myocardium / metabolism
  • Myocardium / pathology*
  • Sarcoglycans / genetics
  • Sarcoglycans / metabolism
  • Ventricular Dysfunction, Left / pathology
  • Ventricular Dysfunction, Left / physiopathology

Substances

  • Calcium Channel Blockers
  • Sarcoglycans
  • Hydroxybutyrate Dehydrogenase
  • Creatine Kinase
  • Diltiazem