Hamilton J T, Zhou Y, Gelb A W
Department of Anaesthesia, University Hospital, University of Western Ontario, London, Canada.
Anesthesiology. 1990 Dec;73(6):1252-7. doi: 10.1097/00000542-199012000-00025.
Since the increase in intracranial pressure produced by succinylcholine is temporally associated with intravenous administration, we investigated in vitro a possible direct cerebrovascular effect of this nicotinic drug. Isometric responses were recorded from dog and guinea pig basilar artery rings suspended in modified Krebs' solution at 37 degrees C. After precontracting with a voltage (KCl)- or a receptor (5-hydroxytryptamine)-mediated agonist, cumulative concentration-relaxation curves were established for: pure succinylcholine; Quelicin from multidose vials containing 20 mg/ml succinylcholine, 1.8 mg/ml methylparaben, and 0.2 mg/ml propylparaben; Anectine from single-dose vials containing 20 mg/ml succinylcholine; multidose Anectine containing 20 mg/ml succinylcholine and 1.0 mg/ml methylparaben; and methylparaben and propylparaben alone. When required, the endothelium of dog artery was removed by gentle mechanical rubbing and the response to the drugs reevaluated. Both Quelicin and multidose Anectine produced statistically significant (P less than 0.05) relaxation; Quelicin was the more potent of the two. Methylparaben and propylparaben produced relaxation in an additive manner and completely accounted for the relaxation produced by Quelicin and multidose Anectine. The vascular relaxation was found to be independent of the presence of a functional endothelium. Consistent with a nicotinic induced contraction, pure succinylcholine maintained vessel tone. It is concluded that the pharmaceutically ubiquitous preservatives methylparaben and propylparaben but not pure succinylcholine have vasoactive properties in vitro.
由于琥珀酰胆碱引起的颅内压升高与静脉给药在时间上相关，我们在体外研究了这种烟碱类药物可能存在的直接脑血管效应。在37℃下，记录悬浮于改良克雷布斯溶液中的犬和豚鼠基底动脉环的等长反应。在用电压（氯化钾）或受体（5-羟色胺）介导的激动剂预收缩后，建立了以下物质的累积浓度-舒张曲线：纯琥珀酰胆碱；来自含有20mg/ml琥珀酰胆碱、1.8mg/ml对羟基苯甲酸甲酯和0.2mg/ml对羟基苯甲酸丙酯的多剂量瓶的奎利松；来自含有20mg/ml琥珀酰胆碱的单剂量瓶的阿库氯铵；含有20mg/ml琥珀酰胆碱和1.0mg/ml对羟基苯甲酸甲酯的多剂量阿库氯铵；以及单独的对羟基苯甲酸甲酯和对羟基苯甲酸丙酯。必要时，通过轻柔的机械摩擦去除犬动脉的内皮，并重新评估对药物的反应。奎利松和多剂量阿库氯铵均产生了具有统计学意义（P<0.05）的舒张；两者中奎利松的作用更强。对羟基苯甲酸甲酯和对羟基苯甲酸丙酯以相加的方式产生舒张，并且完全解释了奎利松和多剂量阿库氯铵产生的舒张。发现血管舒张与功能性内皮的存在无关。与烟碱诱导的收缩一致，纯琥珀酰胆碱维持血管张力。得出的结论是，药学上普遍存在的防腐剂对羟基苯甲酸甲酯和对羟基苯甲酸丙酯在体外具有血管活性特性，而纯琥珀酰胆碱则没有。
