Adherence of leucocytes to electrically damaged venules in vivo. Effects of iloprost, PGE1, indomethacin, forskolin, BW 755 C, sulotroban, hirudin, and thrombocytopenia

Abstract

Increased adherence of leucocytes to the vessel wall is thought to be a key event in potentially deleterious leucocyte-vessel wall interactions in a variety of diseases associated with microvasculatory dysfunction. As measured by videomicroscopy in mesenteric venules (phi 40 +/- 8 microns) of anaesthetized rats, an injury caused by one short electrical stimulus to the venule wall led to a prolonged increase of marginated (sticking and rolling) leucocytes from 228/mm2 to 797/mm2 without affecting red cell velocity and shear rate. Iloprost (0.1 micrograms/kg/min i.v.), PGE1 (2.0 micrograms/kg/min i.a.), BW 755 C (40 mg/kg s.c.), forskolin (0.3 mg/kg i.v.), and hirudin (500 IU/kg + 200 IU/kg/h i.v.) all significantly attenuated injury-induced leucocyte margination. Indomethacin (10 mg/kg s.c.) had no effect and sulotroban (0.5 mg/kg/min) showed borderline efficacy. Platelet depletion by rat antiplatelet serum completely inhibited increased leucocyte margination. PGI2 mimetics, drugs interfering with lipoxygenase metabolism, and thrombin inhibitors may therefore be useful to prevent exaggerated leucocyte-vessel wall interactions.