Thromb Haemost 2010; 104(05): 1022-1028
DOI: 10.1160/TH10-04-0241
Wound Healing and Inflammation/Infection
Schattauer GmbH

Argatroban administration reduces leukocyte adhesion and improves capillary perfusion within the intestinal microcirculation in experimental sepsis

Christian Fuchs
1  Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
,
Elena Ladwig
1  Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
,
Juan Zhou
2  Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
,
Dragan Pavlovic
1  Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
,
Kristina Behrend
1  Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
,
Sara Whynot
2  Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
,
Orlando Hung
2  Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
,
Michael Murphy
2  Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
,
Vladimir Cerny
3  Department of Anesthesiology and Intensive Care Medicine, University Hospital Hradec Kralove, Charles University in Prague, Czech Republic
,
Christian Lehmann
1  Department of Anesthesia and Intensive Care Medicine, Ernst-Moritz-Arndt-Universität, Greifswald, Germany
2  Department of Anesthesia, Dalhousie University, Halifax, Nova Scotia, Canada
› Author Affiliations
Financial support: The study was supported by an unrestricted grant from Mitsubishi Pharma Deutsch-land GmbH.
Further Information

Publication History

Received: 20 April 2010

Accepted after major revision: 19 July 2010

Publication Date:
24 November 2017 (online)

Summary

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. ARG administration in CASP rats significantly increased functional capillary density in mucosal (+128%) and muscular layers (longitudinal: +42%; circular: +64%) and decreased the number of firmly adhering leukocytes in the intestinal submucosa compared to untreated animals. In vitro findings indicated a vasodilating effect of ARG. ARG administration during experimental sepsis improved intestinal microcirculation by preserving functional capillary density, an indicator of microvascular perfusion, and by reducing leukocyte adherence to the endothelium in submucosal venules.