Docetaxel and prostaglandin E 1 (PGE 1 ) increase transcapillary albumin extravasation and reduce interstitial fluid pressure in the skin. In this study the microdialysate concentration (C m ) 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 µl/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 = 5) increased C m of 125 I-HSA and EPP of sizes 73, 65, 56, and 39 Å significantly ( P < 0.05) compared with control. PGE 1 (20 µg/ml, n = 6) increased C m of 125 I-HSA significantly ( P < 0.05) but none of the different-sized EPP was increased compared with control. Intravenous RS (20 ml, n = 6) increased C m of 125 I-HSA and increased all the different-sized EPP significantly ( P < 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 permeability-surface 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 Address for reprint requests and other correspondence: B. Å. Borge, Dept. of Biomedicine, Section of Physiology, Univ. of Bergen, Jonas Lies vei 91, N-5009 Bergen, Norway (email: firstname.lastname@example.org )
AJP - Heart and Circulatory Physiology – The American Physiological Society
Published: May 1, 2006
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