Lung vascular permeability: inferences from measurements of plasma to lung lymph protein transport

In chronically instrumented unanesthetized sheep, we measured steady-state hemodynamic and lung lymph responses to mechanically increased pressure and to intravenous infusions of histamine, Pseudomonas bacteria and E. coli endotoxin. Histamine, Pseudomonas bacteria and E. coli endotoxin caused exchanging vessel permeability to increase, as evidenced by high flows of protein rich lung lymph. This contrasts to the effects of increased pressure where lymph protein concentration falls as lymph flow increases. Microvascular sieving of proteins less than 100 Angstrom radius persisted in all increased permeability states, but with endotoxin, lymph clearance of larger proteins increased much more than with histamine or Pseudomonas. We compared several approaches to quantitative interpretations of lymph data and found that direct methods for calculating permeability-surface area products and reflection coefficients for proteins produced values which were difficult to interpret, probably because fundamental assumptions of the methods were violated in our experiments. A mathematical model based on multiple pore theory produced more plausible coefficients.