Continuous measurements of plasma protein extravasation with microdialysis after various inflammatory challenges in rat and mouse skin

Abstract

This study describes the use of microdialysis technique for continuous measurement of plasma protein extravasation (PPE) in rat and mouse skin with drug application either intravenously or via the microdialysis fiber. Hollow plasmapheresis fibers (3-cm length, 0.4-mm diameter, cutoff 3,000 kDa) were placed subcutaneously on the back of anesthetized mice and rats. Intravenous injection of dextran (Macrodex, 60 mg/ml) increased PPE by 355% from baseline within 30 min in rats with ligated kidneys ( n = 6; P < 0.05) but not in animals with intact kidneys. Phalloidin (500 μg/kg iv 40 min before dextran, n = 6; P < 0.05) did not change the response to dextran in either group. Animals receiving PGE₁, compound 48/80 (mice), paclitaxel, docetaxel, and cremophor EL via the microdialysis fiber were also provided with a control fiber receiving vehicle. Both rats and mice had constant PPE in the control fiber, and there was no change in PPE in the NaCl-treated groups (rats, n = 4; mice, n = 6). Application via the fiber of PGE₁(20 μg/ml), compound 48/80 (mice; 4 mg/ml), and docetaxel (0.5 mg/ml) increased PPE compared with baseline within 60 min by 139% ( n = 6; P < 0.05), 273% ( n = 6; P < 0.05), and 325% ( n = 5; P < 0.05), respectively. Phalloidin alone did not increase PPE ( n = 5; P < 0.05). Pretreatment with phalloidin did not inhibit the increase after PGE₁or compound 48/80 but inhibited that after docetaxel ( n = 6). Paclitaxel (0.6 mg/ml, n = 5) or vehicle (Cremophor) ( n = 5) gave no increase in PPE. The results demonstrate that microdialysis can be used to continuously measure changes in PPE after inflammatory challenges in skin of rats and mice.