STUDIES ON PROPHYLAXIS AGAINST HYPEROXIC LUNG INJURY

预防高氧性肺损伤的研究

• 批准号: 04670924
• 负责人: OBARA Hidefumi
• 金额: $ 1.22万
• 依托单位: KOBE UNIVERSITY
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for General Scientific Research (C)
• 财政年份: 1992
• 资助国家: 日本
• 起止时间: 1992 至 1993
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-04670924/
• 关键词: Oxygen Toxicity; Respiratory Failure; Reactive Oxygen Species; Pulmonary Surfactant; Superoxide Dismutase; Cytokines; Lidocaine; Neutrophil

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

高氧会导致急性肺损伤，导致人类出现成人呼吸窘迫综合征。中性粒细胞通过释放活性氧在高氧肺损伤的发病机制中起关键作用。利多卡因和表面活性剂已被证明可抑制中性粒细胞产生ROS。本研究的目的是确定利多卡因（L）或肺表面活性物质（SF）预处理是否减轻高氧诱导的兔急性肺损伤。[研究1]将动物分为3组：第1组：用空气通气36小时而不进行L处理，第2组：用100%氧气通气36小时而不进行L处理，第3组：用100%氧气通气36小时而进行L处理。在L处理组中，在开始暴露于100%氧气后立即静脉注射单剂量L（2 mg/kg），此后以2 mg/kg/hr的速率输注L 36 h，直至处死动物。所有家兔的肺均 ...更多信息 用100%氧气或空气通风。记录通气期间的血流动力学、PaO_2和肺力学。观察暴露后肺力学、支气管肺泡灌洗液（BALF）中细胞比例、活化补体（C3 a、C5 a）、细胞因子（TNF、IL-1）的变化，并以肺湿/干重（W/D）和BALF中白蛋白浓度作为肺水肿的指标。我们还比较了三组的光镜检查结果。100%氧疗36小时对血流动力学、肺力学和PaO_2/FiO_2比值无明显影响。在36小时暴露期结束时，高氧显著增加肺W/D重量比，中性粒细胞流入肺，BALF中的C3 a，C5 a，TNF，IL-1和白蛋白减弱了这些增加。暴露于100%氧可引起广泛的肺形态学损害，L。[研究2] SF治疗组家兔在100%氧气中通气36小时，并在机械通气开始后12小时经气管给予SF（120 mg/kg）。生理盐水组除给予生理盐水外，其余均给予生理盐水处理，人工通气期间血流动力学、肺力学和动脉血氧分压均无明显变化，BALF中白蛋白、C3 a和W/D重量比生理盐水组均高于SF组。光学显微镜观察发现，在盐水处理的兔子，透明膜形成，但较少的变化，观察SF-治疗group.In的结论，这些研究1和2的结果表明，静脉注射L和支气管内SF有预防作用的初始高氧肺损伤（肺血管通透性，组织病理学和生化BALF的变化）在兔。少

项目成果

Mikawa K.: "Perioperative changes in plasma C_3a and C_5a Concentrations in infants" Paediatric Anaesthesia. 2. 123-131 (1992)

Mikawa K.：“婴儿血浆 C_3a 和 C_5a 浓度的围手术期变化”小儿麻醉。

J.Ikegaki: "Effects of surfactant on lung injury induced by hyperoxia and mechaniacal ventilation in rabbits." Journal of Anesthesia. 7. 68-74 (1993)

J.Ikegaki：“表面活性剂对兔子高氧和机械通气引起的肺损伤的影响。”

K.Mikawa: "Improvement of gas exchange following endobronchial instillation of an exogenous surfactant in an infant with respiratory failure by postoperative pulmonary haemorrhage." Intensive Care Medicine. 20. 58-60 (1994)

K.Mikawa：“对于术后肺出血导致呼吸衰竭的婴儿，支气管内滴注外源性表面活性剂后，气体交换得到改善。”

H.Obara: "Respiratory management for neonatal chronic respiratory failure (BPD)" Intensive and Critical Care Medicine. 4. 565-577 (1992)

H.Obara：“新生儿慢性呼吸衰竭（BPD）的呼吸管理”重症监护医学。

Mikawa K: "Attenuation of the cardiovascular and catecholamine responses to tracheal intubation with oral guanabenz" Anesthesia and Analgesia. 76. 585-591 (1993)

Mikawa K：“口服瓜那苯减弱心血管和儿茶酚胺对气管插管的反应”麻醉和镇痛。