|Budget Amount *help
¥1,900,000 (Direct Cost : ¥1,900,000)
Fiscal Year 1993 : ¥1,100,000 (Direct Cost : ¥1,100,000)
Fiscal Year 1992 : ¥800,000 (Direct Cost : ¥800,000)
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.
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
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.
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