Transvascular clearance and distribution of charged macromolecules in ANTU lung injury

Tissue uptake, extravascular distribution volumes, and plasma-lymph equilibration of two isozymes of lactate dehydrogenase (LDH) were labeled with radioiodine and studied in dogs with either normal or injured lungs. Cationic LDH 5 [isoelectric point (pI) = 7.9] was initially cleared from plasma by lung tissue at a rate 1.61 times higher (9.3 vs. 5.8 X 10(-3) ml X min-1 X g-1 extravascular wet wt) than anionic LDH 1 (pI = 5.0). LDH 5 also had a significantly higher extravascular distribution volume but equilibrated more slowly between plasma and pulmonary lymph (t1/2 = 120 min) than LDH 1 (t1/2 = 78 min) in normal lungs. Respective lymph-to-plasma ratios were 0.53 and 0.43 for LDH 1 and LDH 5 after 4 h of infusion. Infusion of the isozymes 2 h after injection of alpha-naphthylthiourea (ANTU) resulted in larger initial tissue plasma clearances for both isozymes compared with control, but greater relative tissue plasma clearances and extravascular distribution volumes for LDH 5 compared with LDH 1. Plasma-lymph equilibration half times of LDH 5 and LDH 1 were reduced after ANTU to 50 min and 41 min, respectively, whereas the respective alveolar fluid-to-plasma ratios of the two isozymes at termination of the ANTU experiments were 0.56 and 0.84. These data suggest that the fixed anionic charges on endothelial cell surfaces, intercellular junctions, basement membranes, and interstitial structures act much like a cation exchange gel to rapidly take up cationic proteins and retard the plasma-lymph equilibration of these proteins relative to anionic proteins of the same size.(ABSTRACT TRUNCATED AT 250 WORDS)