Grim M, Rerábková L, Carlson B M
Institute of Anatomy, Charles University Medical Faculty, Prague, Czechoslovakia.
Toxicol Pathol. 1988;16(4):432-42. doi: 10.1177/019262338801600403.
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.
以向大鼠胫前肌标准浸润0.1 ml局部麻醉剂作为模型，以帮助选择检测药物肌肉毒性的标准。使用的麻醉剂有0.2%的卡波卡因、1%和2%的利多卡因、0.5%的布比卡因、1%和2%的甲卡因、1%和2%的普鲁卡因。监测肌酸激酶血清水平24小时，并在1个月内监测肌肉的重量以及大体和微观变化。肌肉暴露于局部麻醉剂会导致两种类型的损伤。一种以注射区域的选择性肌纤维损伤为特征。另一种损伤类型是全身性的，涉及多种细胞类型。为了评估药物的肌肉毒性，我们定义了损伤类型、其大小以及随后的肌肉再生速率。我们推荐以下标准用于检测正在开发为药物制剂的新药的肌毒性：1）肌肉注射药物1小时后的血清肌酸激酶水平；2）第3、7和21天的微观检查结果；3）第3天损伤的横截面积；4）第7和21天肌肉的重量。
