Fujinaga M, Baden J M, Mazze R I
Department of Anesthesia, Stanford University School of Medicine, California.
Anesthesiology. 1992 Jun;76(6):999-1003. doi: 10.1097/00000542-199206000-00021.
Evidence of developmental toxicity of clinically used nondepolarizing muscle relaxants was sought in rat embryos grown in culture. Embryos were explanted at 8 AM on day 9 of gestation (presomite stage, plug day = day 0), and were cultured in rotating bottles with medium containing various concentrations of d-tubocurarine, pancuronium, atracurium, and vecuronium. At 10 AM on day 11 of gestation (forelimb bud stage), culture was terminated and embryos were examined for general morphology. Treatment with tested agents resulted in dose-dependent developmental toxicity; namely, growth retardation seen as decreased crown-rump length, decreased number of somite pairs, and morphologic abnormalities. However, the concentrations that caused toxicity were at least 30-fold greater than serum concentrations clinically achieved in the mother. We conclude that these muscle relaxants have a low potential for causing developmental toxicity during organogenesis.
在体外培养的大鼠胚胎中探寻临床使用的非去极化肌松药的发育毒性证据。在妊娠第9天上午8点（前体节期，交配日=第0天）取出胚胎，并在旋转瓶中培养，培养基中含有不同浓度的d-筒箭毒碱、泮库溴铵、阿曲库铵和维库溴铵。在妊娠第11天上午10点（前肢芽期）终止培养，并检查胚胎的总体形态。用受试药物处理导致剂量依赖性发育毒性；即生长迟缓表现为顶臀长度减少、体节对数减少和形态异常。然而，引起毒性的浓度至少比临床上母亲体内达到的血清浓度高30倍。我们得出结论，这些肌松药在器官发生过程中引起发育毒性的可能性较低。
