Argatroban administration reduces leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation in experimental sepsis
Abstract
Co-activation of pro-coagulatory pathways in sepsis may result in disseminated intravascular coagulation and contributes to microvascular dysfunction. We investigated the effects of the direct thrombin inhibitor, argatroban (ARG), on the sepsis-induced impairment of the intestinal microcirculation (capillary perfusion, leukocyte adhesion) and the vascular contractility in rats.
Forty male Lewis rats were randomly assigned to one of four groups: sham surgery (SHAM), experimental sepsis (colon ascendens stent peritonitis - CASP), CASP+ARG, and SHAM+ARG. At 16 hours after colon stent insertion (or sham surgery), 2 mg/kg argatroban or buffer were given intravenously, and 1 hour thereafter, intravital microscopy was performed.
In addition, experiments to study the impact of ARG on vascular contractility were conducted in vitro.