Oxidants and antioxidants in the pathogenesis of chronic lung disease of prematurity

Reactive oxygen species and other radicals (e.g. peroxynitrite) are thought to play a role in the development of chronic lung disease of prematurity (CLD). I hypothesised that serial BAL may washout surfactant and cause persistent radiological changes. I also hypothesised that cellular antioxidants were depleted, and nitric oxide production was increased, in bronchoalveolar lavage fluid (BALF) from infants who developed CLD. Furthermore, my aim was to develop a technique to quantitate nitrite and nitrate in small (<50 microlitres) samples of BALF. 1 studied three groups of infants (those who developed CLD, those who recovered from respiratory distress syndrome (RDS), and control infants ventilated for surgical reasons) and (a) determined the safety of the BAL procedure, (b) developed methods to estimate nitric oxide (NO) products, (c) estimated nitrate and nitrite in BALF and (d) measured glutathione, urate and ascorbate in BALF and plasma. My data showed that serial BAL did not adversely affect radiological appearances. I studied several techniques for reducing nitrite to nitrate, and the Griess reaction and fluorometry to quantitate nitrite. I applied a modified enzymatic method, with fluorometric detection to measure NO products. BALF nitrate concentration was similar in all groups during the first week of life. Thereafter, nitrate concentration was significantly higher (p<0.05) in infants who developed CLD compared to those who did not. Nitrite concentration did not show any trends. There was a delayed increase in BALF ascorbate in the CLD group when compared to the RDS and Control groups. The BALF: plasma ratio of ascorbate was higher in the RDS group at 4 days of age than in the CLD group, suggesting that more mature infants have a better ability to concentrate ascorbate in their lungs. In summary, I noted differences in nitrate and ascorbate concentrations between infants who developed CLD, and those who didn't.