Effects of anticoagulant treatment on intestinal ischaemia and reperfusion injury in rats

Abstract

Background: In recent years it has become increasingly clear that a cross‐talk between the inflammatory response and blood coagulation exists, although many of the underlying mechanisms remain unclear. In the present study we investigated the potential anti‐inflammatory properties of two different anticoagulant compounds, i.e. active‐site inactivated FVIIa (FVIIai) and fondaparinux sodium, a selective FXa inhibitor, administered as pretreatment in a model of intestinal I/R in rats. Methods: Endothelial barrier permeability was assessed using the vascular leakage of radiolabelled human serum albumin, tissue neutrophil sequestration was quantitated by myeloperoxidase (MPO) activity, and plasma levels of macrophage inflammatory protein (MIP)‐2 were examined using an enzyme‐linked‐immuno‐sorbent assay after 40 min of intestinal ischaemia and 6 h of reperfusion in the rat (n = 34). Pretreatment with FVIIai or fondaparinux sodium was administered 90 min before initiation of ischaemia. Results: Endothelial‐barrier permeability in all examined organs, myeloperoxidase activity in the lungs, and ileum and MIP‐2 levels in plasma increased after intestinal I/R. Pretreatment with FVIIai decreased the endothelial barrier permeability and MPO activity in the ileum, and a tendency towards decreased permeability was also observed in the lungs. Fondaparinux did not affect the endothelial barrier permeability or MPO activity. Both FVIIai and fondaparinux decreased the MIP‐2 levels in plasma after intestinal I/R. Conclusions: Inhibition of the TF‐FVIIa complex by FVIIai can attenuate inflammatory responses in connection with intestinal I/R‐injury and could represent a potentially important therapeutic strategy for the prevention of organ dysfunction. Potential anti‐inflammatory properties of fondaparinux and other inhibitors of FXa are not excluded and need further investigation.

Oral Administration of Lactoferrin Attenuates Intestinal Ischemia-Reperfusion Injury in Rats

“…Intestinal I/R induced by SMA occlusion results in the release of destructive proinflammatory cytokines, such as TNF-α, IL-1β and IL-6 and oxygen free radicals into the circulation, subsequently causing the systemic inflammatory response syndrome, a leading cause of morbidity and mortality during critical illness [5,24]. Here we have demonstrated that intestinal I/R markedly elevated serum levels of TNF-α, IL-1β and IL-6, in accordance with our previous report [5], and preoperative administration of Lf significantly reduced their levels.…”

Intestinal Ischemia-Reperfusion Injury Alters Purinergic Receptor Expression in Clinically Relevant Extraintestinal Organs

“…While this devastating progression is common, currently there are no directed therapeutic options available, and clinicians are forced to rely upon supportive measures to treat these patients (13). Although several therapeutic strategies have suggested benefit in the laboratory setting (14)(15)(16)(17), none of these interventions have gained clinical significance in the treatment of humans.…”

Effects of Preoperative Glycyrrhizin Infusion for the Prevention of Venous Thrombosis on the Tissue Expression of Antithrombin in a Rat Model

“…7) The clinical dose and administration method of fondaparinux are 5-7.5 mg/day and a subcutaneous injection, respectively, and its dose was 0.2 mg/kg (subcutaneous injection) in a study on intestinal ischemia-reperfusion in rats by Olanders et al,26) suggesting that the dose (1.5 mg/kg) administered to rats in our study was comparatively high for animal experiments. 'Inflammation' and venous thrombosis are cross-linked.…”

“…Fondaparinux did not inhibit venous thrombosis in the present study, and this may have been due to its weaker inhibitory effects on endothelial cell impairment, which subsequently occurs after 'inflammation' in a cascade initiated by the adhesion of neutrophils to the vascular endothelium at the local stressed site because of the absence of the inhibitory effects of fondaparinux on enhanced vascular endothelial permeability or MPO activity. 26) …”