Metabolic myopathy produced by dinitrofluorobenzene inhibition of creatine phosphokinase.

A previously developed animal model of exercise-induced muscle contractures, which utilized intra-aortic injection of iodoacetate (IOA) to inhibit the second stage glycolytic enzyme glyceraldehyde-3-phosphate dehydrogenase, showed histological evidence of selective type II muscle fiber involvement with sparing of the type I muscle fibers. A new model has been developed using dinitrofluorobenzene (DNFB) as a selective inhibitor of creatine phosphokinase in a similar, but slightly modified distal aortic injection protocol. Two hours after the injection of a dinitrofluorobenzene solution of 2.22 mg/kg body weight, spontaneous electrically-silent contracture developed in the injected lower extremity, involving principally the soleus muscle. Histologically, selective damage was apparent in the type I muscle fibers, with sparing of the type II muscle fibers. The contrast in findings associated with iodoacetate inhibition of glycolysis or with DNFB inhibition of the phosphocreatine shuttle suggests that type I and type II fibers have markedly different usable pools of readily available ATP: type II fibers must rely on the minute-by-minute replenishment of the usable pool of ATP from glycolysis, while type I fibers must regenerate the usable pool of ATP from phosphocreatine through a creatine phosphokinase-mediated process.