Antelman S M, DeGiovanni L A, Kocan D
Department of Psychiatry, University of Pittsburgh School of Medicine, PA 15213.
Life Sci. 1989;44(3):201-7. doi: 10.1016/0024-3205(89)90596-1.
Exposure of rats to one injection of cocaine (35 mg/kg, i.p.) or a single four-hour period of immobilization protected them from the virtually instantaneous death but not from the later, seizure-related death seen in untreated controls following administration of the local anesthetic, tetracaine, 1-4 weeks later. These data suggest that when appropriately timed, strong sympathomimetic stimulation--whether generated by an environmental stressor or a drug--can provide long-lasting protection against the sudden cardiac death potential of local anesthetics. As such, they provide a means for understanding why the incidence of sudden cardiac arrest from one such agent--cocaine itself--is not higher and suggest that an individual's stress history may play a key role in determining vulnerability to the cardiotoxic effect of this compound.
给大鼠注射一次可卡因(35毫克/千克,腹腔注射)或使其经历单次4小时的固定应激,可保护它们免于在1至4周后给予局部麻醉剂丁卡因时几乎即刻发生的死亡,但不能防止后来与癫痫发作相关的死亡,而未接受处理的对照大鼠会出现这种情况。这些数据表明,在适当的时间,强烈的拟交感神经刺激——无论是由环境应激源还是药物引起的——都可以为局部麻醉剂所致的心源性猝死风险提供持久的保护。因此,这些数据有助于理解为何可卡因这类药物导致的心源性猝死发生率没有更高,并表明个体的应激史可能在决定对该化合物心脏毒性作用的易感性方面起关键作用。