PULMONARY INTERSTITIAL PRESSURE AND PROTEOGLYCANS DURING DEVELOPMENT OF PULMONARY-EDEMA

In anesthetized adult rabbits, pulmonary perivascular interstitial pre ssure (P-ip), measured by micropuncture technique with intact pleural space, averaged -10.5 +/- 1.9 (SD) cmH(2)O in control conditions, with a wet-to-dry lung weight ratio (W/D) of 4.8 +/- 0.2, Saline infusion (120 ml iv over 120 min) induced interstitial edema, increasing P-ip t o 3.62 +/- 1.6 cmH(2)O with no significant increase in W/D (5.13 +/- 0 .1). For intravenous saline infusion exceeding 140 ml, P-ip decreased to about-atmospheric pressure with development of severe edema that wa s characterized by an increase of W/D (>7) with no further change in P -ip. In a separate set of animals, pulmonary interstitial proteoglycan s (PGs) were investigated after sequential extraction of the tissue wi th 0.4 and 4 M guanidinium chloride (GuHCl) under control conditions a nd with interstitial (100 ml saline load in 100 min) and severe edema (>200 ml total infusion). The extractability of PGs increased constant ly with increasing W/D. PG content in total extracts was evaluated by determination of hexuronate content which was 195.4 +/- 1.5 mu g/g dry tissue in control lungs, 217.9 +/- 1.6 in interstitial edema, and 316 .4 +/- 2.7 in severe edema. Moreover, edema development was coupled wi th an increase in efficiency of PG extraction with 0.4 M GuHCl. These findings suggested a weakening of PG interactions with other component s of the extracellular matrix (ECM). Electrophoretic and gel-filtratio n analyses showed that the relative content of PG populations of large molecular size decreased constantly in 0.4 M GuHCl extract with incre asing water loading. We propose relating the inflection of P-ip in the transition from interstitial to severe edema to PG breakdown, which m ight greatly affect ECM structural organization, including collagen sp reading and/or rupture of epithelial layer.