与异氟烷相比，七氟烷可使大鼠肺部急性呼吸窘迫综合征的肺损伤降至最低，但对肺外急性呼吸窘迫综合征则无此作用。

Sevoflurane, Compared With Isoflurane, Minimizes Lung Damage in Pulmonary but Not in Extrapulmonary Acute Respiratory Distress Syndrome in Rats.

作者信息

Araújo Mariana N, Santos Cíntia L, Samary Cynthia S, Heil Luciana B B, Cavalcanti Vinicius C M, Cruz Fernanda F, Felix Nathane S, Silva Johnatas D, Morales Marcelo M, Pelosi Paolo, Fernandes Fatima C, Villela Nivaldo R, Silva Pedro L, Rocco Patricia R M

机构信息

From the *Laboratory of Pulmonary Investigation, Carlos Chagas Filho Biophysics Institute; †Department of Surgical Sciences and Integrated Diagnostics; ‡Center of Experimental Surgery, Department of Surgery, School of Medicine; §Laboratory of Cellular and Molecular Physiology, Carlos Chagas Filho Institute of Biophysics, Federal University of Rio de Janeiro, Rio de Janeiro, Brazil; ‖Department of Surgical Sciences and Integrated Diagnostics, Istituto di Ricovero e Cura a Carattere Scientifico, Azienda Ospedaliera Universitaria, San Martino-IST, University of Genoa, Genoa, Italy; ¶Division of Anesthesiology, Department of Surgery, State University of Rio de Janeiro, Rio de Janeiro, Brazil.

出版信息

Anesth Analg. 2017 Aug;125(2):491-498. doi: 10.1213/ANE.0000000000001927.

DOI:10.1213/ANE.0000000000001927

PMID:28277329

Abstract

BACKGROUND

Volatile anesthetics modulate inflammation in acute respiratory distress syndrome (ARDS). However, it is unclear whether they act differently depending on ARDS etiology. We hypothesized that the in vivo and in vitro effects of sevoflurane and isoflurane on lung damage would not differ in pulmonary (p) and extrapulmonary (exp) ARDS.

METHODS

Twenty-four Wistar rats were randomized to undergo general anesthesia (1-2 minutes) with sevoflurane and isoflurane. Animals were then further randomized to receive Escherichia coli lipopolysaccharide (LPS) intratracheally (ARDSp) or intraperitoneally (ARDSexp), and 24 hours after ARDS induction, they were subjected to 60 minutes of sevoflurane or isoflurane anesthesia at 1 minimal alveolar concentration. The primary outcome measure was interleukin (IL)-6 mRNA expression in lung tissue. Secondary outcomes included gas exchange, lung mechanics, histology, and mRNA expression of IL-10, nuclear factor erythroid 2-related factor-2 (Nrf2), surfactant protein (SP)-B, vascular cell adhesion molecule-1, epithelial amiloride-sensitive Na-channel subunits α and γ, and sodium-potassium-adenosine-triphosphatase pump subunits α1 (α1-Na,K-ATPase) and β1 (β1-Na,K-ATPase). Additional ARDSp and ARDSexp animals (n = 6 per group) were anesthetized with sodium thiopental but not mechanically ventilated (NV) to serve as controls. Separately, to identify how sevoflurane and isoflurane act on type II epithelial cells, A549 human lung epithelial cells were stimulated with LPS (20 µg/mL) for 24 hours, and SP-B expression was quantified after further exposure to sevoflurane or isoflurane (1 minimal alveolar concentration ) for 60 minutes.

RESULTS

In ARDSp, sevoflurane reduced IL-6 expression to a greater degree than isoflurane (P = .04). Static lung elastance (P = .0049) and alveolar collapse (P = .033) were lower in sevoflurane than isoflurane, whereas Nrf2 (P = .036), SP-B (P = .042), and β1-Na,K-ATPase (P = .038) expressions were higher in sevoflurane. In ARDSexp, no significant differences were observed in lung mechanics, alveolar collapse, or molecular parameters between sevoflurane and isoflurane. In vitro, SP-B expression was higher in sevoflurane than isoflurane (P = .026).

CONCLUSIONS

Compared with isoflurane, sevoflurane did not affect lung inflammation in ARDSexp, but it did reduce lung inflammation in ARDSp.

摘要

背景

挥发性麻醉药可调节急性呼吸窘迫综合征（ARDS）中的炎症反应。然而，尚不清楚它们的作用是否因ARDS的病因不同而有所差异。我们假设七氟烷和异氟烷对肺损伤的体内和体外作用在肺源性（p）和肺外源性（exp）ARDS中并无差异。

方法

将24只Wistar大鼠随机分为接受七氟烷和异氟烷全身麻醉（1 - 2分钟）的两组。然后将动物进一步随机分为经气管内给予大肠杆菌脂多糖（LPS）（ARDSp）或腹腔内给予（ARDSexp），在诱导ARDS 24小时后，它们在1个最低肺泡浓度下接受60分钟的七氟烷或异氟烷麻醉。主要观察指标是肺组织中白细胞介素（IL）-6 mRNA的表达。次要观察指标包括气体交换、肺力学、组织学以及IL-10、核因子红细胞2相关因子2（Nrf2）、表面活性蛋白（SP）-B、血管细胞黏附分子-1、上皮阿米洛利敏感钠通道亚基α和γ以及钠钾腺苷三磷酸酶泵亚基α1（α1-Na，K-ATP酶）和β1（β1-Na，K-ATP酶）的mRNA表达。另外的ARDSp和ARDSexp动物（每组n = 6）用硫喷妥钠麻醉但不进行机械通气（NV）作为对照。另外，为了确定七氟烷和异氟烷如何作用于II型上皮细胞，用LPS（20 µg/mL）刺激A549人肺上皮细胞24小时，在进一步暴露于七氟烷或异氟烷（1个最低肺泡浓度）60分钟后对SP-B表达进行定量。

结果

在ARDSp中，七氟烷比异氟烷更能显著降低IL-6的表达（P = .04）。七氟烷组的静态肺弹性（P = .0049）和肺泡萎陷（P = .033）低于异氟烷组，而七氟烷组的Nrf2（P = .036）、SP-B（P = .042）和β1-Na，K-ATP酶（P = .038）表达更高。在ARDSexp中，七氟烷和异氟烷在肺力学、肺泡萎陷或分子参数方面未观察到显著差异。在体外，七氟烷组的SP-B表达高于异氟烷组（P = .026）。