Nishina K, Mikawa K, Maekawa N, Takao Y, Obara H
Department of Anesthesiology, Kobe University School of Medicine, Japan.
Anesthesiology. 1995 Jul;83(1):169-77. doi: 10.1097/00000542-199507000-00020.
It is well known that endotoxin causes acute lung injury, resulting in adult respiratory distress syndrome. Lidocaine pretreatment has recently been shown to attenuate endotoxin-induced lung injury in rabbits. The aim of the current study was to determine whether early postinjury treatment with intravenous lidocaine could attenuate acute lung injury induced by endotoxin in rabbits.
Thirty-two male anesthetized rabbits were randomly assigned to receive one of four treatments (n = 8 for each group): infusion of saline (group S-S), infusion of saline with lidocaine treatment (group S-L), infusion of Escherichia coli endotoxin (100 micrograms.kg-1 over a 60-min period) without lidocaine treatment (group E-S), or infusion of endotoxin with lidocaine treatment (group E-L). Ten minutes after the end of infusion of endotoxin (groups E-L and E-S) or saline (groups S-S and S-L), the animals received a bolus injection followed by continuous infusion of lidocaine (2 mg.kg-1 + 2 mg.kg-1.h-1 in groups S-L and E-L) or saline (groups S-S and E-S). The rabbits' lungs were ventilated with 40% O2. Hemodynamics, peripheral leukocyte and platelet counts, and arterial O2 tension (PaO2) were recorded during the ventilation period (6 h). After the observation, lung mechanics; the cell fraction of bronchoalveolar lavage fluid (BALF); and concentrations of activated complement components C3a and C5a, cytokines, and arachidonic acid metabolites in BALF were measured and analyzed. The ratio of lung wet weight to dry weight (W/D weight ratio) and albumin concentrations in BALF were analyzed as indexes of pulmonary edema. The Cypridina luciferin analogue-dependent chemiluminescence (representing O2 production) by neutrophils isolated from the pulmonary artery and light-microscopic findings of the lung were compared among the four groups.
Endotoxin caused decreases in peripheral leukocyte and platelet counts, lung compliance, and PaO2. It caused increases in lung W/D weight ratio; polymorphonuclear cell counts in BALF; and albumin, C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, and thromboxane B2 concentrations in BALF. Lidocaine attenuated the changes in W/D weight ratio and morphologic lung damage. The change in compliance, decrease in PaO2, and albumin concentrations in BALF were slightly but significantly less in rabbits receiving lidocaine after injury. The Cypridina luciferin analogue-dependent chemiluminescence by neutrophils was greater in rabbits receiving endotoxin without lidocaine than in those receiving endotoxin with lidocaine.
These results indicate that early treatment with lidocaine attenuates endotoxin-induced lung edema in rabbits without affecting chemical mediators in BALF. However, the improvement is slight and likely to be of little clinical significance.
众所周知，内毒素可导致急性肺损伤，进而引发成人呼吸窘迫综合征。最近有研究表明，利多卡因预处理可减轻兔内毒素诱导的肺损伤。本研究的目的是确定伤后早期静脉注射利多卡因是否能减轻兔内毒素诱导的急性肺损伤。
32只雄性麻醉兔随机分为四组接受不同处理（每组n = 8）：输注生理盐水（S-S组）、输注生理盐水并给予利多卡因治疗（S-L组）、输注大肠杆菌内毒素（60分钟内输注100微克·千克-1）且不给予利多卡因治疗（E-S组）、输注内毒素并给予利多卡因治疗（E-L组）。在内毒素（E-L组和E-S组）或生理盐水（S-S组和S-L组）输注结束10分钟后，动物接受一次推注，随后持续输注利多卡因（S-L组和E-L组为2毫克·千克-1 + 2毫克·千克-1·小时-1）或生理盐水（S-S组和E-S组）。兔肺用40%氧气进行通气。在通气期间（6小时）记录血流动力学、外周白细胞和血小板计数以及动脉血氧张力（PaO2）。观察结束后，测量并分析肺力学、支气管肺泡灌洗液（BALF）的细胞成分、BALF中活化补体成分C3a和C5a、细胞因子以及花生四烯酸代谢产物的浓度。分析肺湿重与干重之比（W/D重量比）和BALF中的白蛋白浓度作为肺水肿的指标。比较四组从肺动脉分离的中性粒细胞的海萤荧光素类似物依赖性化学发光（代表氧气产生）以及肺的光镜检查结果。
内毒素导致外周白细胞和血小板计数、肺顺应性和PaO2降低。它导致肺W/D重量比、BALF中多形核细胞计数以及BALF中白蛋白、C3a、C5a、肿瘤坏死因子-α、白细胞介素（IL）-1β、IL-6、IL-8和血栓素B2浓度升高。利多卡因减轻了W/D重量比的变化和肺形态学损伤。伤后接受利多卡因的兔肺顺应性变化、PaO2降低以及BALF中白蛋白浓度虽有轻微但显著减轻。接受内毒素但未接受利多卡因的兔中性粒细胞的海萤荧光素类似物依赖性化学发光比接受内毒素并接受利多卡因的兔更强。
这些结果表明，利多卡因早期治疗可减轻兔内毒素诱导的肺水肿，且不影响BALF中的化学介质。然而，改善程度轻微，可能临床意义不大。
