Bronchial microdialysis of cytokines in the epithelial lining fluid in experimental intestinal ischemia and reperfusion before onset of manifest lung injury.

This thesis describes the stepwise development of a new method for monitoring the dynamic composition of the epithelial lining fluid in bronchi in large animals and humans. The starting point was the belief that existing methods had significant limitations. Existing methods were invasive and their use created lung injury or failed to measure substances of interest. The idea was to find a method for continuous measurement that did not harm patients. The method was to be evaluated monitoring lung involvement in organ crosstalk after experimental intestinal ischemia-reperfusion injury and during aortic surgery.The first paper evaluated microdialysis in the bronchi and blood in an experimental setting with controlled blood-concentration of one small substance (lactate) and one larger substance (fluorescein-isothiocyanate-dextran 4000Da). We concluded that bronchial microdialysis could measure concentration of substances within the bronchial epithelial lining fluid. The use of the concentration gradient of an endogenous correction factor (urea) improved the accuracy. In the second paper we used bronchial microdialysis to describe the inflammatory response in the bronchi in a pig model of intestinal ischemia-reperfusion injury. We found an increase in the bronchial concentration of inflammatory mediators within the first 60 minutes of intestinal reperfusion after intestinal ischemia. The third paper was a study of the inflammatory response in patients undergoing aortic surgery. A broad spectrum of inflammatory markers was measured in bronchi and blood during and immediately after surgery. Inflammatory mediators increased within the first 60 minutes of reperfusion of the lower body when the aortic graft was in place. The concentrations of seventeen out of eighteen inflammatory mediators, as measured by bronchial microdialysis, were significantly different in patients suffering organ failure directly after surgery.The thesis concluded by answering the thesis questions and claims that bronchial microdialysis is feasible in pigs and humans, can be done with no registered complications and is able to measure the dynamics of inflammatory mediators in the bronchi. However the method needs further evaluation of methods to ease secure placement of the probe, measure the absolute concentration of substances in the bronchial epithelial lining fluid. The delay in analysis of cytokines needs to be significantly reduced to take advantage of the results in support for expedited clinical judgement.