Canine X-linked muscular dystrophy studied with in vivo phosphorus magnetic resonance spectroscopy.
Duchenne muscular dystrophy (DMD) is an X-linked disease characterized by progressive muscle weakness and degeneration. Dystrophin is the product of the missing gene in this disorder. However, the cause of the dystrophic process is not understood. Transient muscle injury is normally seen after muscle exercise, and may be a necessary process in muscle growth and preservation. We, therefore, chose to evaluate the role of exercise in Duchenne dystrophy by studying the canine X-linked animal model (CXMD). These dogs also lack dystrophin and have clinical signs similar to humans. Exercise was initiated by electrical stimulation, and muscle metabolism was monitored with phosphorus magnetic resonance spectroscopy (P-MRS). Dogs with CXMD had abnormal muscle pathology and markedly elevated serum CK. The inorganic phosphate (Pi) to phosphocreatine (PCr) ratio was increased in CXMD dogs at rest compared with normal dogs (Pi/(Pi + PCr) = 0.166 +/- 0.054 for CXMD and 0.073 +/- 0.017 for normals, mean +/- SE). No changes in resting ATP, pH, phosphomonoesters (PME), and phosphodiesters (PDE) were seen. The mean Pi/(Pi + PCr) and pH values during stimulation were normal in the CXMD dogs. Two to three days after electrical stimulation, resting Pi/(Pi + PCr) ratios were significantly increased in the CXMD dogs (0.127 +/- 0.029 compared with 0.172 +/- 0.054, mean +/- SD). Normal dogs showed no increase in Pi/(Pi + PCr) following stimulation. There was a 50-fold greater increase in serum CK in CXMD compared with normal dogs following exercise. These results indicate greater muscle injury in CXMD muscle, and suggest that in the absence of dystrophin, exercise-induced muscle injury may play a role in the dystrophic process.
McCully
K
K
Department of Biochemistry and Biophysics, University of Pennsylvania, Philadelphia 19104.
Giger
U
U
Argov
Z
Z
Valentine
B
B
Cooper
B
B
Chance
B
B
Bank
W
W
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D003402:Creatine Kinase / Q000378:metabolism; D004285:Dogs; D008040:Genetic Linkage; D006863:Hydrogen-Ion Concentration; D009682:Magnetic Resonance Spectroscopy; D008297:Male; D009132:Muscles / Q000378:metabolism*; D009137:Muscular Dystrophy, Animal / Q000235:genetics / Q000378:metabolism*; D010710:Phosphates / Q000378:metabolism; D010725:Phosphocreatine / Q000378:metabolism; D005082:Physical Exertion; D014960:X Chromosome
D010710:Phosphates; D010725:Phosphocreatine; D000255:Adenosine Triphosphate; D003402:Creatine Kinase