Motsch J, Hennis P J, Zimmermann F A, Agoston S
Department of Experimental Surgery, Universities of Leiden, The Netherlands.
Anesthesiology. 1989 Jan;70(1):128-33. doi: 10.1097/00000542-198901000-00024.
Hepatic uptake and distribution of nondepolarizing muscle relaxants in pigs was investigated. A portocaval shunt preparation enabled the determination of the pharmacodynamics of nondepolarizing muscle relaxants both during temporary liver exclusion and intraportal injection in the same animal. To demonstrate the validity of the model in pigs, in a pilot study the influence of hepatic uptake on neuromuscular blockade by pancuronium (n = 3) and its congener Org 6368 (n = 3) was determined. Thereafter, the influence of hepatic uptake on neuromuscular blockade by gallamine (3.4 mg/kg, n = 5), Org 6368 (0.3 mg/kg, n = 5), and vecuronium (0.1 mg/kg, n = 4 and 0.15 mg/kg, n = 5) was studied in pigs anesthetized with pentobarbital. Each pig received one relaxant, which was injected four consecutive times under different conditions. The first injection was into the jugular vein (iv) the second into the portal vein, the third was iv while the liver was excluded for 10 min and the fourth was iv (control). After each injection the onset time, intensity, recovery rate, and total duration of neuromuscular blockade were measured. These variables were compared between the four injections for each relaxant. In the pilot study the influence of hepatic uptake on neuromuscular blockade was similar for pancuronium and Org 6368. For gallamine the onset time, intensity, recovery rate, and duration of action were similar after all four injections. For Org 6368 the variables of neuromuscular blockade were similar after iv and intraportal injection, but exclusion of the liver prolonged the neuromuscular block.(ABSTRACT TRUNCATED AT 250 WORDS)
研究了非去极化肌松药在猪体内的肝摄取和分布情况。门腔分流制备方法能够在同一动物体内临时排除肝脏期间和门静脉内注射时测定非去极化肌松药的药效学。为了证明该模型在猪体内的有效性，在一项初步研究中确定了肝摄取对泮库溴铵（n = 3）及其同类物Org 6368（n = 3）神经肌肉阻滞的影响。此后，在戊巴比妥麻醉的猪中研究了肝摄取对加拉明（3.4 mg/kg，n = 5）、Org 6368（0.3 mg/kg，n = 5）和维库溴铵（0.1 mg/kg，n = 4和0.15 mg/kg，n = 5）神经肌肉阻滞的影响。每头猪接受一种肌松药，在不同条件下连续注射四次。第一次注射入颈静脉（静脉注射），第二次注入门静脉，第三次在排除肝脏10分钟时静脉注射，第四次静脉注射（对照）。每次注射后测量神经肌肉阻滞的起效时间、强度、恢复率和总持续时间。比较每种肌松药四次注射之间的这些变量。在初步研究中，泮库溴铵和Org 6368的肝摄取对神经肌肉阻滞的影响相似。对于加拉明，所有四次注射后的起效时间、强度、恢复率和作用持续时间相似。对于Org 6368，静脉注射和门静脉内注射后神经肌肉阻滞变量相似，但排除肝脏会延长神经肌肉阻滞。（摘要截断于250字）
