Quantitative assessment of microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs

We quantitatively assessed the change of pulmonary microvascular permeability following E. coli endotoxin infusion (1 mg/kg) in anaesthetized dogs. We used mathematical analysis to estimate membrane parameters from lung lymph data. Lung lymph was collected from the afferent lymphatic connecting to the left tracheobronchial lymph node whose lymph could be considered to represent an average sample of lung tissue fluid. To separate the effects of changes in the driving pressures and surface area on lymph fluid and protein flux from those in membrane permeability, lymph flow (Jv) was increased greater than 6 times baseline by left atrial pressure (Pla) elevation until lymph protein concentration (CL) approached to a constant value independent of Jv. Membrane parameters for plasma total protein, i.e., osmotic reflection coefficient (sigma d), solvent-drag reflection coefficient (sigma f), permeability surface area product (PS), filtration coefficient (Kfc), were calculated from lung lymphatic data in control (Pla elevation alone (n = 10), and endotoxin group (n = 7). Among these parameters, osmotic reflection coefficient (sigma d) decreased significantly to 0.61 in endotoxin group from the value of 0.71 in control group. This result indicates a moderate increase in pulmonary microvascular permeability following E. coli endotoxin infusion. However, there was no significant difference in the other membrane parameters (sigma f, PS, Kfc) between control and endotoxin group. Based on these results, we conclude that sigma d could quantitatively represent the moderate change of the microvascular permeability in endotoxin-induced lung injury in anaesthetized dogs.