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)