BACKGROUND: Superoxide dismutase (SOD) has been shown to attenuate hyperoxic lung injury. This effect is thought to be exhibited by scavenging superoxide released from neutrophils and other aerobic cells. The aim of the current study was to investigate the effect of pre-treatment with SOD on the chemical mediators in hyperoxic lung injury. METHODS: Thirty male anesthetized rabbits were allocated to receive one of three treatments (n = 10 for each group): ventilated with 100% oxygen for 36 h with or without recombinant human SOD (rhSOD) treatment, and ventilated with air for 36 h without rhSOD. In the rhSOD-treated group, a single intravenous dose of rhSOD 10,000 U kg BW-1 was administered immediately after the start of exposure to 100% oxygen and thereafter infused at a rate of 340,000 U kg BW-1 day-1 for 36 h until the animals were sacrificed. The lungs of all rabbits were ventilated with 100% oxygen or air. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure to 100% oxygen, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolite concentrations in BALF were measured and analyzed. The lung wet-to-dry (W/D) weight ratio and albumin concentrations in BALF were determined as indices of pulmonary oedema. RESULTS: Exposure to the high concentration of oxygen for 36 h caused no significant changes in haemodynamics but decreased compliance and increased A-aDo2. In the rhSOD-treated group, the decrease in compliance was not observed. At the end of the 36 hr-exposure period, however, hyperoxia significantly increased the lung W/D weight ratio, influx of neutrophils into the lung, BALF concentrations of C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, thromboxane B2, and albumin. Pre-treatment with rhSOD attenuated these increases. Exposure to 100% oxygen caused extensive morphologic lung damage (alveolar haemorrhage and hyaline membrane formation), which was lessened by rhSOD. CONCLUSION: These results indicate that intravenous rhSOD prevented hyperoxic lung injury (decreases in PaO2 and compliance, increased pulmonary vascular permeability, histopathological damage) in rabbits. This prophylactic effect of rhSOD amy be due, in part, to decreased chemical mediators such as activated complements, cytokines, and arachidonic acid metabolites.
BACKGROUND:Superoxide dismutase (SOD) has been shown to attenuate hyperoxic lung injury. This effect is thought to be exhibited by scavenging superoxide released from neutrophils and other aerobic cells. The aim of the current study was to investigate the effect of pre-treatment with SOD on the chemical mediators in hyperoxic lung injury. METHODS: Thirty male anesthetized rabbits were allocated to receive one of three treatments (n = 10 for each group): ventilated with 100% oxygen for 36 h with or without recombinant humanSOD (rhSOD) treatment, and ventilated with air for 36 h without rhSOD. In the rhSOD-treated group, a single intravenous dose of rhSOD 10,000 U kg BW-1 was administered immediately after the start of exposure to 100% oxygen and thereafter infused at a rate of 340,000 U kg BW-1 day-1 for 36 h until the animals were sacrificed. The lungs of all rabbits were ventilated with 100% oxygen or air. Haemodynamics, PaO2, and lung mechanics were recorded during the ventilation period. After exposure to 100% oxygen, lung mechanics, cell fraction of bronchoalveolar lavage fluid (BALF), activated complements, cytokines, and arachidonic acid metabolite concentrations in BALF were measured and analyzed. The lung wet-to-dry (W/D) weight ratio and albumin concentrations in BALF were determined as indices of pulmonary oedema. RESULTS: Exposure to the high concentration of oxygen for 36 h caused no significant changes in haemodynamics but decreased compliance and increased A-aDo2. In the rhSOD-treated group, the decrease in compliance was not observed. At the end of the 36 hr-exposure period, however, hyperoxia significantly increased the lung W/D weight ratio, influx of neutrophils into the lung, BALF concentrations of C3a, C5a, tumor necrosis factor-alpha, interleukin (IL)-1 beta, IL-6, IL-8, thromboxane B2, and albumin. Pre-treatment with rhSOD attenuated these increases. Exposure to 100% oxygen caused extensive morphologic lung damage (alveolar haemorrhage and hyaline membrane formation), which was lessened by rhSOD. CONCLUSION: These results indicate that intravenous rhSOD prevented hyperoxic lung injury (decreases in PaO2 and compliance, increased pulmonary vascular permeability, histopathological damage) in rabbits. This prophylactic effect of rhSOD amy be due, in part, to decreased chemical mediators such as activated complements, cytokines, and arachidonic acid metabolites.
Authors: A B Waxman; O Einarsson; T Seres; R G Knickelbein; J B Warshaw; R Johnston; R J Homer; J A Elias Journal: J Clin Invest Date: 1998-05-01 Impact factor: 14.808