Department of Anesthesiology, First Hospital of Lanzhou University, Lanzhou, 730000, People's Republic of China.
Department of Anesthesiology, The University of Hong Kong, Hong Kong, 999077, People's Republic of China.
BMC Anesthesiol. 2020 Aug 1;20(1):188. doi: 10.1186/s12871-020-01089-5.
Long-term mechanical ventilation with hyperoxia can induce lung injury. General anesthesia is associated with a very high incidence of hyperoxaemia, despite it usually lasts for a relatively short period of time. It remains unclear whether short-term mechanical ventilation with hyperoxia has an adverse impact on or cause injury to the lungs. The present study aimed to assess whether short-term mechanical ventilation with hyperoxia may cause lung injury in rats and whether deferoxamine (DFO), a ferrous ion chelator, could mitigate such injury to the lungs and explore the possible mechanism.
Twenty-four SD rats were randomly divided into 3 groups (n = 8/group): mechanical ventilated with normoxia group (MV group, FiO = 21%), with hyperoxia group (HMV group, FiO = 90%), or with hyperoxia + DFO group (HMV + DFO group, FiO = 90%). Mechanical ventilation under different oxygen concentrations was given for 4 h, and ECG was monitored. The HMV + DFO group received continuous intravenous infusion of DFO at 50 mg•kg•h, while the MV and HMV groups received an equal volume of normal saline. Carotid artery cannulation was carried out to monitor the blood gas parameters under mechanical ventilation for 2 and 4 h, respectively, and the PaO/FiO ratio was calculated. After 4 h ventilation, the right anterior lobe of the lung and bronchoalveolar lavage fluid from the right lung was sampled for pathological and biochemical assays.
PaO in the HMV and HMV + DFO groups were significantly higher, but the PaO/FiO ratio were significantly lower than those of the MV group (all p < 0.01), while PaO and PaO/FiO ratio between HMV + DFO and HMV groups did not differ significantly. The lung pathological scores and the wet-to-dry weight ratio (W/D) in the HMV and HMV + DFO groups were significantly higher than those of the MV group, but the lung pathological score and the W/D ratio were reduced by DFO (p < 0.05, HMV + DFO vs. HMV). Biochemically, HMV resulted in significant reductions in Surfactant protein C (SP-C), Surfactant protein D (SP-D), and Glutathion reductase (GR) levels and elevation of xanthine oxidase (XOD) in both the Bronchoalveolar lavage fluid and the lung tissue homogenate, and all these changes were prevented or significantly reverted by DFO.
Mechanical ventilation with hyperoxia for 4 h induced oxidative injury of the lungs, accompanied by a dramatic reduction in the concentrations of SP-C and SP-D. DFO could mitigate such injury by lowering XOD activity and elevating GR activity.
长期接受高浓度氧机械通气可导致肺损伤。全身麻醉与高氧血症的发生率非常高相关，尽管它通常持续相对较短的时间。目前尚不清楚短期高浓度氧机械通气是否会对肺部造成不良影响或导致肺损伤。本研究旨在评估短期高浓度氧机械通气是否会导致大鼠肺损伤，以及去铁胺（DFO），一种亚铁离子螯合剂，是否可以减轻这种肺损伤，并探讨可能的机制。
24 只 SD 大鼠随机分为 3 组（n = 8/组）：常氧机械通气组（MV 组，FiO = 21%）、高氧机械通气组（HMV 组，FiO = 90%）或高氧+DFO 组（HMV + DFO 组，FiO = 90%）。在不同氧浓度下进行机械通气 4 小时，并监测心电图。HMV + DFO 组连续静脉输注 DFO 50mg•kg•h，而 MV 和 HMV 组给予等体积生理盐水。分别在机械通气 2 小时和 4 小时时进行颈总动脉插管监测血气参数，并计算 PaO/FiO 比值。通气 4 小时后，取右肺前段和右肺支气管肺泡灌洗液进行病理和生化检测。
HMV 和 HMV + DFO 组的 PaO 明显升高，但 PaO/FiO 比值明显低于 MV 组（均 p < 0.01），而 HMV + DFO 组和 HMV 组的 PaO 和 PaO/FiO 比值无显著差异。HMV 和 HMV + DFO 组的肺病理评分和湿重/干重比值（W/D）明显高于 MV 组，但 DFO 降低了肺病理评分和 W/D 比值（p < 0.05，HMV + DFO 与 HMV 相比）。在生化方面，HMV 导致肺泡灌洗液和肺组织匀浆中表面活性蛋白 C（SP-C）、表面活性蛋白 D（SP-D）和谷胱甘肽还原酶（GR）水平降低，黄嘌呤氧化酶（XOD）水平升高，而这些变化均被 DFO 预防或显著逆转。
4 小时高浓度氧机械通气可导致肺氧化损伤，同时 SP-C 和 SP-D 浓度显著降低。DFO 可通过降低 XOD 活性和提高 GR 活性来减轻这种损伤。
