Studies on nitric oxide in the respiratory system

Sammanfattning: STUDIES ON NITRIC OXIDE IN THE RESPIRATORY SYSTEM Ulla Schedin, MD, Dissertation from the Division of Anaesthesiaand Intensive Care, Karolinska Institute Danderyd Hospital, S-182 88, Danderyd, Sweden Nitric oxide (NO) is formed in biological tissues and has regulatory functionsin many organ systems. Endogenous NO has been found in exhaled air and NO is consideredto have effects on the pulmonary circulation and bronchial tone, and to be one ofthe mediators for the circulatory adaptation at birth. Exogenous NO inhalation hasbeen administered to patients with acute lung injury and pulmonary hypertension.but with varying responses and is not yet an approved therapy. The role of NO inthe respiratory system is still unclear. Objectives. A better understanding of NO in the respiratory system undernormal- and pathophysiological conditions. Material. Human adults with healthy and sick lungs. Premature and healthyterm neonates. Several different animal species, domestic animals as well as wildanimals at a zoo. Methods. Endogenous airway NO concentrations were measured by chemiluminescence.Analysers with different response times and sampling flow rates were utilised inmeasurements of mixed exhaled air, after timed occlusions and in single breaths.Exhaled gas from different parts of the airways was studied. Two clinically usedmethods, chemiluminescence and electrochemical techniques, were evaluated by measurementsin clinically relevant gas mixtures, containing up to 80 ppm NO in oxygen. Results. The measured NO concentrations were dependent on sampling site,gas flow, and measuring technique. In adults, significant but low tracheal NO concentrationswere measured, a few parts per billion (ppb), whereas nasal NO levels were severalhundred times higher. All neonates, term as well as preterm infants, displayed highnasal NO concentrations, up to 4.6 parts per million (ppm) after timed occlusionsalready within a few minutes after birth, independent of mode of delivery. NasalNO concentrations had increased 4-7 days after birth in term infants and were alsorelated to the postconceptional age of the preterm infants. In animals we found agreat difference in nasal NO concentrations between species. NO levels comparablewith humans were only found in other primates (Rhesus monkey, chimpanzee and gorilla)and in elephant. Rhesus monkey and pig were studied in more detail and displayedquite different excretion pattern. Both chemiluminescence and electrochemical cellswere found to be suitable for monitoring during NO inhalation therapy. Without precautions,toxic NO2 levels, up to 5 ppm, may be formed in a ventilatory circuit in hyperoxicNO-rich gas mixtures. Conclusions. In humans, NO is excreted from the respiratory system withthe highest concentrations from the nose. An autoinhalation from the upper to thelower airways is possible and might effect the pulmonary vessels. The high nasalNO concentrations, up to 4.6 ppm, found in neonates might be important for the circulatoryadaptation at birth and indicates that at least some tissue is adapted to such NOlevels. Microbes is not a prerequisite for nasal NO excretion as it was found alreadywithin a few minutes after delivery by Caesarean section. The great species differencesin nasal NO concentrations could not be related to differences in upper airway anatomyor living conditions. To extrapolate animal data to humans might be hazardous andso far only primates seem to be suitable for such studies. Key words: nitric oxide, endogenous, respiratory system, neonate, prematureinfant, animal, primate, elephant, chemiluminescence, electrochemical, nitrogen dioxide,trachea, nose, ISBN 91-628-2769-3