Pulmonary clearance of 99mTc-DTPA: role of the pulmonary surfactant system.

It is established that in a wide variety of acute and chronic lung diseases the integrity of the alveolar-capillary membrane is altered. Increased permeability of the barrier is thought to cause increased filtration of fluids and proteins into the alveoli and increased absorption of inhaled substances into the blood stream. This can eventually lead to impaired gas exchange and, therefore, deterioration of tissue oxygenation. Attempts to elucidate the nature of changes occurring in the alveolar-capillary barrier has led to increasing research with radio-labelled tracer molecules, such as technetium-99m-labelled diethylene triamine pentaacetic acid (99mTc-DTPA) and technetium-99m-labelled human serum albumin r99mTc-HSA), in order to measure the permeability of this membrane. The alveolar-capillary membrane consists of lour layers, namely; the alveolar surfactant layer, the alveolar ep~helium, the interstitium with basement membrane, and the vascular endothelium. It is generally agreed that the epithelium is the main rate-limiting factor in determining permeability and, therefore, limiting the ability of different solutes to transfer across this barrier. Results of recent research indicate that the alveolar surfactant layer may also be a rate-limiting factor for solutes and, therefore, is of importance to the permeability of this membrane. This thesis focuses on the significance of the surfactant layer on permeability measurements with radio-labelled materials and also investigates how different medical interventions, such as artificial ventilation and inhalation anaesthetics, influence permeability of the alveolar-capillary barrier when measured with the described techniques. In addition, the effects of cigarette smoking on surfactant function and ssmTc-DTPA clearance was studied in humans.