Article type: Research Article
Authors: Zhou, Juan | Zimmermann, Katrin | Krieg, Thomas | Soltow, Marieke | Pavlovic, Dragan | Cerny, Vladimir; | Lehmann, Christian
Affiliations: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada | Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Germany | Department of Pharmacology, University of Cambridge, Cambridge, UK | Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Hradec Kralove, Charles University Prague, Prague, Czech Republic
Note: [] Corresponding author: Dr. Christian Lehmann, MD, PhD, FRCPC, Professor, Departments of Anesthesia, Pharmacology, Microbiology and Immunology, Dalhousie University, 10 North Victoria, 1278 Tower Road, Halifax, NS, B3H 2Y9, Canada. Tel.: +1 902 494 1287; Fax: +1 902 494 2493; E-mail: chlehmann@dal.ca
Abstract: Gut ischemia and reperfusion (IR), e.g. in small bowel transplantation or during resuscitation, may result in severe impairment of the intestinal microcirculation. Potential sequelae are mucosal damage, loss of intestinal barrier function, bacterial translocation, systemic inflammation, multiple organ failure and death. We hypothesized a protective role for extracellular adenosine signalling in intestinal IR injury. Using intravital microscopy we investigated the effects of the adenosine receptor (AR) agonist NECA (5′-N-ethyl carboxamide adenosine) on leukocyte-endothelial interactions and capillary perfusion in the intestinal microcirculation following intestinal IR. Six groups of Lewis rats (n = 44) were studied: control, NECA (5′-N-ethyl carboxamide adenosine), IR (30 minutes of intestinal ischemia, 2 hours of reperfusion), IR + NECA, IR + NECA + MRS1754 (A2BAR antagonist), IR + NECA + DPCPX (A1AR antagonist). All substances were administered i.v. immediately after declamping of the superior mesenteric artery. Intravital microscopy was performed after 2 hours of reperfusion. Following IR we observed a significant increase of leukocyte adhesion in the intestinal submucosal venules and a reduced capillary perfusion within the muscular layers. NECA reduced leukocyte activation and improved capillary perfusion significantly. Administration of A2BAR antagonist completely reversed the NECA effect, whereas A1AR inhibition only partially abolished the action of NECA. The data support the hypothesis that adenosine signalling is involved in intestinal IR injury. A2BAR may be more important than A1AR because A2BAR inhibition by MRS1754 completely reversed the effect of the adenosine receptor agonist NECA.
Keywords: Adenosine, adenosine receptor, intestine, microcirculation, intravital microscopy, ischemia, reperfusion, leukocyte adhesion, capillary perfusion, functional capillary density (FCD)
DOI: 10.3233/CH-141846
Journal: Clinical Hemorheology and Microcirculation, vol. 59, no. 3, pp. 257-265, 2015
