A test for muscle lesions and their regeneration following intramuscular drug application.

A standard infiltration of the rat tibialis anterior muscle with 0.1 ml of local anesthetics was used as a model to help choose criteria for testing the intramuscular toxicity of drugs. Anesthetics used were 0.2% carbisocaine, 1% and 2% Lidocaine, 0.5% Marcaine, 1% and 2% Mesocaine, 1% and 2% Procaine. Increases in the serum levels of creatine kinase were monitored for 24 hours, and the weight, as well as macro- and microscopic changes in the muscle for a period of 1 month. Exposure of the muscle to local anesthetics resulted in 2 types of lesions. One was characterized by selective muscle fiber damage in the injected area. The other type of lesion was a generalized one that involved a number of cell types. To assess the intramuscular toxicity of drugs we defined the type of lesion, its size, and the rate of subsequent muscle regeneration. We recommend the following criteria for the assay of myotoxicity of new drugs being developed as pharmaceutical agents: 1) serum creatine kinase level 1 hour after intramuscular injection of the drug; 2) microscopic findings at 3, 7, and 21 days; 3) the cross-sectional area of the lesion at 3 days; and 4) the weight of the muscle at 7 and 21 days.