Solute exhange across the alveolo-capillary barrier

Sammanfattning: The aim of this thesis was to study the transfer of solutes across the alveolo-capillary barrier in experimental models of alveolar surfactant dysfunction and lung injury as well as in smokers. Experimental studies were performed in anaesthetized, and mechanically ventilated animals. Surfactant dysfunction was induced by administration of a synthetic detergent in aerosol form. Lung injury was induced by intravenous injection of oleic acid. A range of radiolabelled solutes were administrered in aerosol form and the clearance of the tracer from the lungs measured with a gamma camera. Detergent administration results in mild pulmonary oedema and has little effect on compliance of the respiratory system and gas exchange. Oleic acid administration produces severe oedema, reduces compliance and impairs gas exchange. The increase in pulmonary clearance of a small, hydrophilic solute was greater after detergent administration than after injection of oleic acid. Surfactant dysfunction dramatically increased the clearance of small, hydropholic solutes, but had little effect on albumin or on small, lipophilic solutes. The effect of detergent administration on clearance of a small, hydrophilic solute could be partly reversed by administration of natural surfactant. The effect of smoking on clearance of small and large solutes was studied in normal subjects. The effect of smoking was qualitatively similar, but the differences between smokers and non-smokers were greater for the small than for the large solute. The studies provide further evidence that the alveolar surfactant system forms part of the alveolo-capillary barrier against exchange of small, hydrophilic solutes. Clearance of larger solutes may to a greater extent reflect the properties of the structural components of the alveolo-capillary barrier.