Exclusion of charged macromolecules in the pulmonary interstitium

The polyanionic glycosaminoglycans and glycoproteins of the interstitial ground substance could influence the interstitial distribution volumes (VA) of plasma proteins filtered across the pulmonary capillaries depending upon the molecular charge of the proteins. To determine if such differences occur, two isozymes of lactate dehydrogenase (LDH) were selectively labeled with either 125I or 131I and infused simultaneously at a rate sufficient to maintain constant plasma concentrations for 24 hr. The isoelectric points of LDH 1 and LDH 5 are 5.0 and 7.9, respectively, but they have the same mol wt (140,000) and hydrodynamic radius (42 A). VA values were calculated in lymph equivalents based on the respective activities in prenodal tracheobronchial lymph. We corrected the residual blood in the tissue using either 99mTc-labeled red cells or Dextran 70 washout of blood. At 24 hr the VA for cationic LDH 5 was significantly greater than that of anionic LDH 1 (0.299 vs 0.197 ml/g wet wt) in the lung. Lymph/plasma ratios for LDH 1 and 5 were not significantly different (0.63 vs 0.58) and total extravascular lung water was not significantly different from normal. This indicates the LDH 1 was excluded from a significantly greater portion (47%) of interstitial fluid than LDH 5 (21%), and suggests an interaction of the fixed negative charges on interstitial polysaccharides with cationic proteins.