Institute of Anesthesiology, University Hospital Zurich Institute of Physiology and Center for Integrative Human Physiology, University of Zurich, Winterthurerstrasse 190, Zurich, Switzerland.
Clin Exp Immunol. 2012 Apr;168(1):125-34. doi: 10.1111/j.1365-2249.2012.04562.x.
Pulmonary oedema is a hallmark of acute lung injury (ALI), consisting of various degrees of water and proteins. Physiologically, sodium enters through apical sodium channels (ENaC) and is extruded basolaterally by a sodium-potassium-adenosine-triphosphatase pump (Na(+) /K(+) -ATPase). Water follows to maintain iso-osmolar conditions and to keep alveoli dry. We postulated that the volatile anaesthetic sevoflurane would impact oedema resolution positively in an in-vitro and in-vivo model of ALI. Alveolar epithelial type II cells (AECII) and mixed alveolar epithelial cells (mAEC) were stimulated with 20 µg/ml lipopolysaccharide (LPS) and co-exposed to sevoflurane for 8 h. In-vitro active sodium transport via ENaC and Na(+) /K(+) -ATPase was determined, assessing (22) sodium and (86) rubidium influx, respectively. Intratracheally applied LPS (150 µg) was used for the ALI in rats under sevoflurane or propofol anaesthesia (8 h). Oxygenation index (PaO(2) /FiO(2) ) was calculated and lung oedema assessed determining lung wet/dry ratio. In AECII LPS decreased activity of ENaC and Na(+) /K(+) -ATPase by 17·4% ± 13·3% standard deviation and 16·2% ± 13·1%, respectively. These effects were reversible in the presence of sevoflurane. Significant better oxygenation was observed with an increase of PaO(2) /FiO(2) from 189 ± 142 mmHg to 454 ± 25 mmHg after 8 h in the sevoflurane/LPS compared to the propofol/LPS group. The wet/dry ratio in sevoflurane/LPS was reduced by 21·6% ± 2·3% in comparison to propofol/LPS-treated animals. Sevoflurane has a stimulating effect on ENaC and Na(+) /K(+) -ATPase in vitro in LPS-injured AECII. In-vivo experiments, however, give strong evidence that sevoflurane does not affect water reabsorption and oedema resolution, but possibly oedema formation.
肺水肿是急性肺损伤 (ALI) 的标志，由不同程度的水和蛋白质组成。从生理学上讲，钠通过顶端钠通道 (ENaC) 进入细胞，然后由钠钾三磷酸腺嘌呤核苷酶泵 (Na(+) / K(+) -ATPase) 将其从基底外侧挤出。水随后进入以维持等渗条件并保持肺泡干燥。我们假设挥发性麻醉剂七氟醚会在 ALI 的体外和体内模型中对水肿的消退产生积极影响。肺泡上皮 II 型细胞 (AECII) 和混合肺泡上皮细胞 (mAEC) 用 20μg/ml 脂多糖 (LPS) 刺激，并同时暴露于七氟醚中 8 小时。通过 ENaC 和 Na(+) / K(+) -ATPase 测定体外主动钠转运，分别评估 (22) 钠和 (86) 铷内流。用气管内给予的 LPS (150μg) 在七氟醚或异丙酚麻醉下的大鼠中建立 ALI (8 小时)。计算氧合指数 (PaO(2) / FiO(2) )，并通过测定肺湿/干比来评估肺水肿。在 AECII 中，LPS 使 ENaC 和 Na(+) / K(+) -ATPase 的活性分别降低了 17.4%±13.3%和 16.2%±13.1%。在七氟醚存在的情况下，这些作用是可逆的。与异丙酚/LPS 组相比，8 小时后，七氟醚/LPS 组的 PaO(2) / FiO(2) 从 189±142mmHg 增加到 454±25mmHg，氧合明显改善。与异丙酚/LPS 处理的动物相比，七氟醚/LPS 组的湿/干比降低了 21.6%±2.3%。七氟醚在 LPS 损伤的 AECII 体外对 ENaC 和 Na(+) / K(+) -ATPase 有刺激作用。然而，体内实验有力地证明，七氟醚不会影响水的重吸收和水肿的消退，但可能会影响水肿的形成。
