Borge, B. Å ., V. V. Iversen, and R. K. Reed. Changes in plasma protein extravasation in rat skin during inflammatory challenges evaluated by microdialysis. Am J Physiol Heart Circ Physiol 290: H2108-H2115, 2006. First published December 22, 2005 doi:10.1152/ajpheart.00395.2005.-Docetaxel and prostaglandin E 1 (PGE1) increase transcapillary albumin extravasation and reduce interstitial fluid pressure in the skin. In this study the microdialysate concentration (Cm) of 125 I-labeled human serum albumin ( 125 I-HSA) and different-sized endogenous plasma proteins (EPP) was compared to evaluate changes in transcapillary extravasation of plasma proteins.125 I-HSA was also used to estimate changes in the specific activity of albumin. Extravasation of 125 I-HSA and EPP from plasma to interstitium in the rat skin was compared during continuous administration of docetaxel and PGE 1 by using microdialysis in anesthetized rats. Also, 20 ml of Ringer solution (RS) were injected intravenously during 10 min in a separate group. Two hollow plasmapheresis fibers (3 cm, cut off 3,000 kDa), one acting as control, were placed subcutaneously on the back skin and perfused with RS (5 l/min, 140 min, collected every 10 min). The size of the different EPP was estimated to be 73, 65, 56, 47, and 39 Å , separated by a size-exclusion high-performance liquid chromatography column and quantified by UV detection (280 nm). Docetaxel (0.5 mg/ml, n ϭ 5) increased Cm of 125 I-HSA and EPP of sizes 73, 65, 56, and 39 Å significantly (P Ͻ 0.05) compared with control. PGE 1 (20 g/ml, n ϭ 6) increased Cm of 125 I-HSA significantly (P Ͻ 0.05) but none of the different-sized EPP was increased compared with control. Intravenous RS (20 ml, n ϭ 6) increased C m of 125 I-HSA and increased all the different-sized EPP significantly (P Ͻ 0.05) compared with control. Although the microdialysis method is able to monitor qualitative changes in capillary permeability, a quantitative determination of the capillary reflection coefficient or permeabilitysurface area product was not possible, because steady state between plasma and dialysate was not achieved during the measurement period. The different pattern of extravasation of EPP and 125 I-HSA after docetaxel, PGE 1, and RS indicates increased interstitial transport rate and/or increased capillary permeability after docetaxel and RS, whereas PGE 1 seems to increase transcapillary fluid flux without altering the permeability.high-performance liquid chromatography; prostaglandin E 1; docetaxel; transcapillary transport QUANTIFICATION of macromolecular passage from plasma to interstitial fluid may give important information of the integrity of the capillary barrier. Many pharmacological agents and pathological conditions have been shown to alter the permeability and/or protein flux across the capillaries in subcutaneous tissue (39) Docetaxel is a microtubule fixating agent and has previously been demonstrated to lower interstitial fluid pressure (P if ) and increase the extravasation of 125