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Modelling neutrophil transit through the human pulmonary circulation

University of British Columbia

The object of this thesis was to construct a model to simulate the arterial, capillary and venous networks of the pulmonary circulation and to compute transit times of red blood cells and neutrophils through the human lung. A complete model of the arterial system was constructed using existing anatomical data for the arterial branching system combined with a set of probabilities to describe the branching nature of the arterial network beyond the existing data. Flow continuity and energy balance equations were used to estimate the total pressure drops through a wide range of possible pathways in this network. When flow had reached the capillary bed, a strictly stochastic model of cell transit through a randomly generated grid network was used to simulate capillary flow. Finally, the flow was returned to the left atrium by modifying the arterial network to represent the venous system. Studies in several species have shown that neutrophils have much longer transit times than red blood cells in the pulmonary circulation. The model described above was used to test the hypothesis that this delay is due to the greater deformability of red blood cells with respect to neutrophils. The results show that erythrocyte transit times are accurately predicted from physical data using the model. However, the neutrophil transit times predicted from the delay which neutrophils experience as they deform to enter smaller capillary segments are shorter than current experimental results. This suggests that factors additional to those that result from cell deformation times delay the neutrophils. These factors could include either receptor-mediated neutrophil adhesion to endothelial cells or the time required for neutrophils to actively move through segments with very low driving pressures. It further suggests that these components are responsible for a major time delay of neutrophils in the pulmonary microcirculation which could not be modelled with currently available data. The results obtained with the model also suggests that the fall in pulmonary vascular resistance and rise in circulating neutrophil count associated with increased pulmonary blood flow could be related to the flushing of neutrophils out of the pulmonary capillary bed.

Thesis/Dissertation

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2009-04-08

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http://hdl.handle.net/2429/6902

Experimental Medicine

University of British Columbia

UBCV

DSpace