STUDIES ON PROPHYLAXIS AGAINST HYPEROXIC LUNG INJURY

高氧会导致急性肺损伤，导致成人呼吸窘迫综合征。中性粒细胞通过释放活性氧(ROS)在高氧性肺损伤的发病机制中发挥关键作用。利多卡因和表面活性物质已被证明能抑制中性粒细胞产生ROS。为探讨利多卡因(L)或肺表面活性物质(SF)预处理对高氧性急性肺损伤的保护作用，将动物分为3组：1组：空气通气组36小时不加L治疗，2组：100%氧气通气组36小时不加L治疗，3组：100%氧气通气组36小时加L治疗。L治疗组，单次静注。在开始100%氧气暴露后立即给予L 2 mg/kg，然后以2 mg/kg/h的速度给L静脉滴注36h，直至处死动物。所有兔的肺组织均为…更通风的是100%的氧气或空气。记录呼吸期血流动力学、动脉血氧分压(PaO2)和肺力学。染毒后分别测定和分析肺力学指标、肺泡灌洗液(BALF)中细胞百分比、活化补体(C3a、C5a)和细胞因子(IL-1、肿瘤坏死因子)，并分析肺湿/干(W/D)比和BALF中白蛋白浓度作为肺水肿的指标。我们还比较了这三组人的光镜发现。100%氧气36小时对血流动力学、肺力学及PaO2/FiO2比值无明显影响。在36小时暴露结束时，高氧显著增加肺W/D重量比，中性粒细胞流入肺内，而BALF-L中的C3a、C5a、肿瘤坏死因子、IL-1和白蛋白则减弱这些增加。暴露于100%氧气中可引起广泛的肺损伤，L可减轻这种损伤。[研究2]SF处理的兔在开始机械通气12小时后，吸入100%氧气36h，气管内给予SF(120 mg/kg)。生理盐水组的血流动力学、肺力学、动脉血氧分压无明显变化，BALF中的白蛋白、补体C3a和湿重/干重比值均高于生理盐水组。光镜下可见生理盐水组兔肺透明膜形成，而SF组变化较小。结论研究1和2结果提示，L静脉注射和SF支气管内注入对兔早期高氧性肺损伤(肺血管通透性、组织病理学和生化BALF改变)具有预防作用。较少

Hyperoxia causes acute lung injury, resulting, in humans, in adult respirtory distress syndrome. Neutrophils are thought to play a pivotal role in the pathogenesis of hyperoxic lung injury through the release of reactive oxygen species (ROS). Lidocaine and surfactant have been shown to inhibit production of ROS by neutrophils. The aim of this study was to determine whether pretreatment with lidocaine (L) or surfactant (SF) attenuated acute lung injury induced by hyperoxia in rabbits.[Study 1]The animals were divided into 3 groups : Group 1 : ventilation with air for 36 hr without L treatment, Group 2 : ventilation with 100% oxygen for 36 hr without L treatment, and Group 3 : ventilation with 100% oxygen for 36 hr with L treatment. In the L-treated group, a single i.v. dose of L (2 mg/kg) was administered immediately after the initiation of exposure to 100% oxygen, thereafter L was infused at a rate of 2 mg/kg/hr for 36 hr until the animals were sacrificed. The lungs of all rabbits were … More ventilated with 100% oxygen or air. Hemodynamics, PaO_2, and lung mechanics were recorded during the ventilation period. After exposure, the lung mechanics and cell fraction in bronchoalveolar lavage fluid (BALF) were measured and analyzed, as was activated complements (C3a and C5a), and cytokines (TNF and IL-1) in BALF.The lung wet-to dry-(W/D) weight ratio and albumin concentrations in BALF were analyzed as an index of pulmonary edema. We also compared light microscopic findings in the three groups. 100% oxygen for 36 hr caused no significant changes in hemodynamics, lung mechanics, or PaO_2/FiO_2 ratio. At the end of the 36-hr exposure period, hyperoxia significantly increased the lung W/D weight ratio, the influx of neutrophils into the lung, and C3a, C5a, TNF, IL-1, and albumin in BALF.L attenuated these increases. Exposure to 100% oxygen caused extensive morphologic lung damage, which was lessened by L.[Study 2]SF-treated rabbits were ventilated with 100% oxygen for 36 hr and SF (120mg/kg) was given via the trachea 12 hr after the start of mechanical ventilation. Saline-treated rabbits were treated idenically, except that they received saline without SF.There were no significant changes in hemodynamics, lung mechanics, or arterial oxygen tension during artificial ventilation.Albumin and C3a in BALF and W/D weight ratio were higher in saline-treated group than in SF-treated group. Light microscopy revealed hyaline membrane formation in saline-treated rabbits, but fewer changes were observed in SF-treated group.In conclusion, these results of Studies 1 and 2 suggest that intravenous L and intrabronchial SF have a prophylactic effect on initial hyperoxic lung injury (pulmonary vascular permeability, histopathological, and biochemical BALF changes) in rabbits. Less