Sinar D R, Carey L C, Cordova C, Fletcher J R, Castell D O
Dig Dis Sci. 1985 Nov;30(11):1085-91. doi: 10.1007/BF01315607.
Intravenous lidocaine was infused at 0.82 ml/min in a concentration of 1.2 mg/ml (2.3 mg/kg) for 120 min in awake chair-restrained baboons (Papio anubis), and measurements of esophageal peristalsis and LES pressure were compared before and after lidocaine or control infusions. Lidocaine produced a progressive and significant (P less than 0.05) decrease in amplitude in the peristaltic wave in the smooth muscle portion of the distal esophagus during the 120-min infusion. Lower esophageal sphincter pressure was similarly significantly lower than control after the infusion of lidocaine (P less than 0.05). Velocity and duration of the peristaltic wave were unchanged during the infusion. The decreased amplitude occurred during therapeutic and stable serum concentrations of lidocaine. It did not appear that the inhibitory effect of lidocaine was due to an induction of prostaglandin synthesis, because pretreatment of animals with indomethacin did not change the inhibitory effect of lidocaine, and serum metabolites of prostacyclin decreased during the infusion. Furthermore, the inhibitory effect of lidocaine was not topical. The response to the muscarinic agonist, bethanechol was similar in lidocaine-treated animals and control animals. The preservation of a bethanechol response after lidocaine inhibition of LES pressure and distal esophageal amplitude suggests that lidocaine acts proximal to the muscarinic receptor in the esophageal body and smooth muscle portion of the lower esophageal sphincter. This study suggests that lidocaine produces an inhibitory effect on the peristaltic wave and lower esophageal sphincter pressure that is similar to inhibitory effects described after anticholinergic agents and calcium channel blocking drugs, but intravenous lidocaine infusion requires a longer period of time to produce inhibition of muscle function.
在清醒且坐在椅子上受到约束的狒狒(埃及狒狒)中,以1.2毫克/毫升(2.3毫克/千克)的浓度、0.82毫升/分钟的速度静脉输注利多卡因,持续120分钟,然后比较利多卡因或对照输注前后食管蠕动和LES压力的测量值。在120分钟的输注过程中,利多卡因使远端食管平滑肌部分蠕动波的幅度逐渐且显著降低(P<0.05)。输注利多卡因后,食管下括约肌压力同样显著低于对照组(P<0.05)。输注过程中蠕动波的速度和持续时间未发生变化。幅度降低发生在利多卡因治疗且血清浓度稳定期间。利多卡因的抑制作用似乎并非由于前列腺素合成的诱导,因为用吲哚美辛预处理动物并未改变利多卡因的抑制作用,且输注过程中前列环素的血清代谢产物减少。此外,利多卡因的抑制作用并非局部性的。利多卡因处理的动物和对照动物对毒蕈碱激动剂氨甲酰甲胆碱的反应相似。利多卡因抑制LES压力和远端食管幅度后仍保留对氨甲酰甲胆碱的反应,这表明利多卡因在食管体部和食管下括约肌平滑肌部分的毒蕈碱受体近端起作用。这项研究表明,利多卡因对蠕动波和食管下括约肌压力产生抑制作用,这与抗胆碱能药物和钙通道阻滞剂后描述的抑制作用相似,但静脉输注利多卡因需要更长时间才能产生肌肉功能抑制。