The present study identifies proteins modified by nitration in the plasma of patients with ongoing acute respiratory distress syndrome (ARDS). The proteins modified by nitration in ARDS were revealed by microsequencing and specific antibody detection to be ceruloplasmin, transferrin, alpha(1)-protease inhibitor, alpha(1)-antichymotrypsin, and beta-chain fibrinogen. Exposure to nitrating agents did not deter the chymotrypsin-inhibiting activity of alpha(1)-antichymotrypsin. However, the ferroxidase activity of ceruloplasmin and the elastase-inhibiting activity of alpha(1)-protease inhibitor were reduced to 50.3 +/- 1.6 and 60.3 +/- 5.3% of control after exposure to the nitrating agent. In contrast, the rate of interaction of fibrinogen with thrombin was increased to 193.4 +/- 8.5% of the control value after exposure of fibrinogen to nitration. Ferroxidase activity of ceruloplasmin and elastase-inhibiting activity of the alpha(1)-protease inhibitor in the ARDS patients were significantly reduced (by 81 and 44%, respectively), whereas alpha(1)-antichymotrypsin activity was not significantly altered. Posttranslational modifications of plasma proteins mediated by nitrating agents may offer a biochemical explanation for the reported diminished ferroxidase activity, elevated levels of elastase, and fibrin deposits detected in patients with ongoing ARDS.

We describe a simple apparatus for analysis of perfluorochemicals (PFC) in expired gas and thus a means for determining PFC vapor and liquid elimination from the respiratory system. The apparatus and data analysis are based on thermal conduction and mass transfer principles of gases. In vitro studies were conducted with the PFC vapor analyzer to determine calibration curves for output voltage as a function of individual respiratory gases, respiratory gases saturated with PFC vapor, and volume percent standards for percent PFC saturation (%PFC-Sat) in air. Voltage-concentration data for %PFC-Sat of the vapor from the in vitro tests were accurate to within 2.0% from 0 to 100% PFC-Sat, linear (r = 0.99, P < 0.001), and highly reproducible. Calculated volume loss of PFC liquid over time correlated well with actual loss by weight (r = 0.99, P < 0. 001). In vivo studies with neonatal lambs demonstrated that PFC volume loss and evaporation rates decreased nonlinearly as a function of time. These relationships were modulated by changes in PFC physical properties, minute ventilation, and postural repositioning. The results of this study demonstrate the sensitivity and accuracy of an on-line method for PFC analysis of expired gas and describe how it may be useful in liquid-assisted ventilation procedures for determining PFC volume loss, evaporation rate, and optimum dosing and ventilation strategy.

No abstract

Inhaled nitric oxide (INO) therapy is currently used clinically to selectively dilate the pulmonary vasculature and to help treat persistent pulmonary hypertension and bronchopulmonary dysplasia in the neonate. However, in the presence of oxygen or superoxide, nitric oxide forms potentially harmful reactive nitrogen species. Using an experimental mice model, we examined the effects of concurrent hyperoxia and INO on protein tyrosine nitration and cysteine S-nitrosylation in pulmonary tissue. Data showed enhanced 3-nitrotyrosine staining within the airway epithelium and alveolar interstitium of mice lungs treated with hyperoxia, which did not increase significantly with INO administration. Within the alveolar interstitium, 3-nitrotyrosine staining was localized to macrophages. S-Nitrosocysteine staining in airway epithelium was significantly enhanced with INO administration regardless of oxygen content. These data suggest that the formation of protein S-nitrosocysteine is the major protein modification during administration of INO.

No abstract