Duchenne muscular dystrophy: functional ischemia reproduces its characteristic lesions.

The highly characteristic early and midstage histological lesions of Duchenne dystrophy were reproduced experimentally in the rat by the combination of a vascular abnormality, aortic ligation, which does not affect the structure of the intramuscular blood vessels, and the humoral vasoactive substance 5-hydroxytryptamine. Neither ligation nor injection of 5-hydroxytryptamine alone causes changes in the muscle fibers. This result establishes the possibility of a similar combined mechanism for a nonstructural ischemia pathogenesis in Duchenne dystrophy. The proposed pathogenesis is contrary to the generally held idea that the cause is an intrinsic abnormality of muscle fiber metabolism.

Erythrocyte shape in Duchenne muscular dystrophy.

In a controlled and blind study we were not able to identify any abnormality of erythrocytes of eight patients with Duchenne muscular dystrophy compared with seven approximately age-matched unaffected siblings (six males, one female step-sibling). Erythrocyte morphology was found to be very sensitive to various types of cell treatment. At this time, erythrocyte morphology, evaluated by the techniques used, should not be considered an established diagnostic test for the Duchenne muscular dystrophy patient or carrier.

99mTc-diphosphonate uptake in skeletal muscle: a quantitative index of acute damage.

In rats with ischemic myopathy induced by aortic ligation and 5-hydroxytryptamine, there was good correlation of the skeletal muscle concentration of 99mTc-diphosphonate with the increase of plasma creatine phosphokinase and the decrease in muscle potassium. This radionuclide tracer method can be used to quantitate acute injury in individual muscles and provides a basis for clinical nuclear imaging in patients with a variety of disorders involving muscle fiber damage.

Localization of technetium-99m diphosphonate in acutely injured muscle. Relationship to muscle calcium deposition.

In rats with experimental ischemic myopathy, there was a significant correlation (r = 0.778, p less than 0.001) between muscle uptake of technetium-99m (99mTc) diphosphonate and tissue calcium concentration. In addition, the accumulation of both calcium and 99mTc-diphosphonate in acutely injured muscles was further increased in rats with vitamin D-induced hypercalcemia. Histologic studies demonstrated staining of damaged muscle fibers with alizarin red, indicating the presence of microcrystalline or ultramicrocrystalline calcium salts. Staining of muscle fibers was most intense in the outer marginal zones of individual microscopic infarcts. Our results suggest that the uptake of 99mTc-diphosphonate in acutely damaged skeletal muscle is directly related to the deposition of calcium salts within the injured muscle fibers.