The Experimental Investigation Of Reoxygenation Injury In Chronically Hypoxia Rat Lungs

Objective: The postoperative course of cyanotic children is generally more complicated than that of acyanotic children. A possible reason is reoxygenation injury at the beginning of cardiopulmonary bypass. In this study we tested the hypothesis that reoxygenation of chronically hypoxia lungs with 100% O2 is worse than those with 21% O2 and investigated the potential role of nuclear factor kappa B (NFκB) activtion and tumor necrosis factor-a in reoxygenation injury of lungs . Methods: Ninty-six male 5-week-old Sprange-Dawley rats weighting 114 ~123g were randomly assigned to 3 equal groups of thirty-two animals: group CH1 and CH2 were exposed for 2 weeks to chronic hypoxia (FiO2=0.10) followed by 1 hours reoxygenation with 100 or 21% O2; group C was exposed to room air for 2 weeks followed by 1 hours reoxygenation with 100% O2. Blood samples and lung tissues were obtained at 0, 1, 3 and 6 hours of reoxygenation for determination of lung water, myelpoeroxidase(MPO) and SOD activities, lung and plasma malondialdehyde (MDA) content, and microscopic examination (light and electron microscopy). By using immunohistochemistry combined with in situ quantitive analysis, the distribution and relative contents of NFκB, IκB in lung were determinded. The total lung homogenates were prepared to detect TNF-a level by ELISA.Results: There were no significant changes in lung water, SOD activities, TNF-a level,malondialdehyde (MDA) content of lung and plasma at 0 h of reoxygenation in the three groups(P>0.05);compared with group C,the expression of NFκB was significantly higher but IκB was lower in group CH(P<0.05). Lung water, lung and plasma malondialdehyde (MDA), and the expression of NFκB and TNFa level in lung tissue in group CH1 were significantly higher than those in group C and group CH2 at 1h, 3h and 6h after reoxygenation, whereas the expression of IκB and SOD activities in group CH1 were significantly lower (P<0.05~0.01). In group CH1, MPO activity in lung tissue was significantly higher than that in group CH2 at 6hafter reoxygenation and in group C at 1h, 3h and 6h after reoxygenation(P<0.05~0.01). Compared with group CH1, the pathologic changes induced by reoxygenation were significantly attenuated in group CH2.Conclusion: Chronically hypoxia reoxygenation can lead to acute lung injury. Activation of NFκB, degradation of IκB, and upregulation of TNF-a expression may play an important role in chronically hypoxia reoxygenation injury in rat lung. During reoxygenation, the degree of lung injury, activation of NFκB, degradation of IκB, and upregulation of TNF-a expression was low with 21% O2 but remain high with 100% O2. We speculate that oxygen should be reintroduced with more caution in chronically hypoxia lungs.