title: Adenosine receptor activation improves microcirculation in experimental intestinal ischemia/reperfusion.
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 (A(2B)AR antagonist), IR + NECA + DPCPX (A(1)AR 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 A(2B)AR antagonist completely reversed the NECA effect, whereas A(1)AR inhibition only partially abolished the action of NECA. The data support the hypothesis that adenosine signalling is involved in intestinal IR injury. A(2B)AR may be more important than A(1)AR because A(2B)AR inhibition by MRS1754 completely reversed the effect of the adenosine receptor agonist NECA.
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Juan
authors.initials: J
authors.lastname: Zhou
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Germany.
authors.forename: Katrin
authors.initials: K
authors.lastname: Zimmermann
authors.affiliation: Department of Pharmacology, University of Cambridge, Cambridge, UK.
authors.forename: Thomas
authors.initials: T
authors.lastname: Krieg
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Germany.
authors.forename: Marieke
authors.initials: M
authors.lastname: Soltow
authors.affiliation: Department of Anesthesia and Intensive Care Medicine, Ernst Moritz Arndt University Greifswald, Germany.
authors.forename: Dragan
authors.initials: D
authors.lastname: Pavlovic
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada Department of Anesthesiology and Intensive Care Medicine, Faculty of Medicine Hradec Kralove, Charles University Prague, Prague, Czech Republic.
authors.forename: Vladimir
authors.initials: V
authors.lastname: Cerny
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: Christian
authors.initials: C
authors.lastname: Lehmann
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D051381:Rats; D011917:Rats, Inbred Lew; D018047:Receptors, Purinergic P1 / Q000235:genetics* / Q000378:metabolism*; D015427:Reperfusion Injury
chemical_list: D018047:Receptors, Purinergic P1
keywords: Adenosine; adenosine receptor; capillary perfusion; functional capillary density (FCD); intestine; intravital microscopy; ischemia; leukocyte adhesion; microcirculation; reperfusion