Regulation of Gas Phase Nitric Oxide (NO) by Ventilation and Pulmonary Blood Flow in Human Lungs

摘要

NO have been demonstrated in exhaled breath of animals and humans and have been increasingly used as markers of a variety of lung pathologies. Despite recent progress in understanding of the physiological regulation of NO, fundamental aspects remain unresolved such as the local and systemic origin of NO, its distribution alongside the airways and regulation of alveolar concentrations. To clarify these issues we investigated the influence of ventilation and pulmonary blood flow on NO concentrations in the lower airways of patients undergoing open heart surgery in exclusion of NO from ambient air and upper airways. This study reveals that concentrations of NO in the lower airways increase as ventilation decrease, suggesting importance of ventilation in eliminating NO from human lungs. In the absence of air flow, NO accumulated rapidly in the main airways reaching plateau levels of app.10 times of end tidal levels within 30 seconds. Breath holding maneuvers followed by inspiration or expiration reveal that alveolar concentrations of NO remain low despite accumulation of NO in the main airways during breath holding, suggesting that NO is continuously removed from the alveoli. Rapid reduction in pulmonary arterial blood flow at instrumentation of cardiopulmonary bypass results in increased NO concentrations in the airways suggesting that pulmonary blood flow is responsible for tonic removal of NO from the lower airways and that NO is not delivered from systemic sources but produced locally within the lungs. The potential significance of these observations on one lung ventilation was tested in patients undergoing thoracic surgery. Measurement of NO concentrations in the non-dependent and dependent lungs demonstrate that one lung ventilation creates a NO gradient between non-ventilated and ventilated lungs in the magnitude of 20-50 fold in favour of the non ventilated lung. This provides the basis for a hypothesis that accumulation of the selective pulmonary vasodilator NO in unventilated lung regions might contribute to the pathophysiology of right to left transpulmonary shunt and hypoxemia in a variety of lung pathologies.