Cl-esterase inhibitor and its effects on endotoxin-induced leukocyte adherence and plasma extravasation in postcapillary venules

Background. C1-esterase inhibitor (C1-INH) has been shown to have beneficia l effects in patients with sepsis. However, the microcirculatory effects of C1-INH during sepsis are unknown. This study investigated the influence of C1-INH on leukocyte-endothelial cell adhesion, vascular leakage, and venul ar microhemodynamics in postcapillary venules of rat mesentery during endot oxemia. Methods. Thirty-two anesthetized Wistar rats randomly received 1 of 4 treat ments: pretreatment with infusion of C1-INH in a concentration of 7.5 U . k g(-1) body weight (C1-INH-7.5 group, n = 8) or in a concentration of 15 U . kg(-1) body weight (C1-INH-15 group, n = 8)followed by continuous infusion of Escherichia coli lipopolysaccharide (LPS). The LPS group (n = 8) was pr etreated with saline solution 30 minutes before LPS infusion. The control g roup (n = 8) received equivalent mounts of saline infusion. Leukocyte adher ence, red blood cell velocity, and vessel diameters in postcapillary venule s of rat mesentery were determined every 60 minutes during a period of 120 minutes using in vivo videomicroscopy. Vascular permeability was determined by measuring the extravasation of fluorescence-labeled albumin. Venular wa ll shear rate was calculated from mean red blood cell velocity and vessel d iameter. Results. LPS infusion induced a decrease in venular wall shear rate and an increase in leukocyte adherence and vascular permeability in postcapillary venules of rat mesentery. All microcirculatory disturbances were attenuated by pretreatment with C1-INH, showing no significant difference between the 2 concentrations. Conclusions. Pretreatment with C1-INH attenuates endotoxin-induced leukocyt e adherence and macromolecular leakage in postcapillary venules of rat mese ntery, indicating that complement inhibition might be a therapeutic tool in the treatment of sepsis.