Increased levels of nitric oxide (NO) have been measured in exhaled gas in a variety of pulmonary pathologies with a prominent inflammatory component. Inflammation with both the appearance of inflammatory cells and elevation of a variety of inflammatory mediators appears to be a consistent component in the pathology of hyaline membrane disease (HMD) and early neonatal chronic lung disease (CLD). We report pulmonary NO production in the baboon model of HMD and CLD. Ten premature baboons, Papio sp., at 140 days (77%) gestation were delivered by hysterotomy and placed on IMV at an FiO2=1.0 (5 animals-induced HMD/CLD), or at an FiO2 adjusted “prn” (5 animals- controls) to maintain normal arterial oxygen levels. Four additional baboons were delivered at 125 days (70%) gestation and were managed on IMV with FiO2 adjusted “prn.” Gas was sampled and measurements were paired from both the proximal limb of the ventilator(<2 ppb), and endotracheally via a double lumen endotracheal tube at hour of life 1,2,4, and every 4 hours until necropsy at 144 or 240 hours. The sampled gas was analyzed by chemiluminescence after verification of baseline with “zero” gas, and calibration to known NO gas standards. The resulting digital signal was recorded and subsequently processed to yield peak NO levels in parts per billion (ppb) for each respiratory cycle. Comparisons were analyzed with one way ANOVA with correction for repeated measures and Student-Newman-Keuls method. Overall mean peak endotracheal NO levels measured at the distal ETT in the two gestational ages were: 140 day gestation prn animals 5.2 ppb (95% confidence interval 0.8 ppb), 125 day gestation prn animals 2.4 ppb (95% confidence interval 0.3 ppb). Comparison at each sampling time revealed a significantly lower (p=0.004) mean peak endotracheal NO levels over the first 28 hours of life in the 70% gestation animals. No statistically significant differences were found between the 140 day gestation prn group and the FiO2=1.0 group. No correlation was found when comparing mean peak endotracheal NO levels with a/AO2 ratio or oxygenation index. Endogenous pulmonary production of NO measured endotracheally in the intubated premature baboon appears to be significantly lower at earlier gestational ages. Despite evidence suggesting the importance of inflammation in the evolution of CLD, exhaled NO levels do not appear to increase in this primate model of neonatal CLD.

funding granl HL 52646