Plasma-lymph exchange and interstitial distribution volumes of charged macromolecules in the lung

The plasma-lymph exchange of two lactate dehydrogenase (LDH) isozymes (4.2 nM) of different molecular charge between plasma (CP) and lung lymph (CL), their initial clearances across the capillary wall, and their extravascular distribution volumes were studied in dog lungs at control and increased left atrial pressures (Pla = 23.3 +/- 2.1 cmH2O). The anionic LDH 1 [isoelectric point (pI) = 5.0] exhibited a more rapid plasma decay compared with cationic LDH 5 (pI = 7.9) after bolus injection but was maintained relatively constant in several experiments using a constant infusion. The mean 10- to 12-min lung tissue clearances were 40% higher for LDH 5 than LDH 1 at control Pla and 120% higher at increased Pla. The CL/CP ratios of the anionic LDH 1 were consistently higher at 4-5 h after simultaneous injection than those of cationic LDH 5. However, the extravascular distribution volumes of LDH 5 were significantly higher in lymph equivalents than those of LDH 1 at 4 h in both Pla groups. Fixed negative charges located on endothelial cells, basement membrane, and interstitial matrix could explain the observed differences between LDH isozymes in CL/CP ratios, tissue uptake, and extra-vascular distribution volumes by the ionic interaction of LDH 5 with these negative change sites which would retard the plasma-lymph transport and enhance the extravascular distribution volume and initial clearance of these cationic macromolecules.