title: Desmopressin improves intestinal functional capillary density and decreases leukocyte activation in experimental endotoxemia.
abstract: BACKGROUND
  Blood flow to the intestine is decreased in sepsis in favor of vital organs resulting in ischemic damage of the gut mucosa. Once the mucosa is damaged, increased translocation of intestinal bacteria to the systemic circulation may occur. This in turn aggravates the inflammatory response contributing to the development of multi-organ failure. Desmopressin is a synthetic analog of vasopressin, an anti-diuretic hormone which has been shown to induce vasodilation and is thought to be implicated in immunomodulation. In this study, we investigate the effects of desmopressin on the intestinal microcirculation during sepsis in an experimental endotoxemia model in rats using intravital microscopy. In addition, we investigate the effects of desmopressin on systemic inflammation.
  
  
  METHODS
  Forty Lewis rats were subdivided into four groups, where rats received intravenous saline (control), desmopressin (1μg/kg/ml), lipopolysaccharide (5mg/kg) or lipopolysaccharide followed by desmopressin. Inflammatory response was assessed by quantifying the number of temporary and firmly adherent leukocytes in submucosal venules. Capillary perfusion was determined by assessing the number of functional, non-functional and dysfunctional capillaries in the intestinal wall layers (muscularis longitudinalis, muscularis circularis and mucosa). Additionally, inflammatory cytokine levels were determined by multiplex assays.
  
  
  RESULTS
  The number of firmly adhering leukocytes in V1 venules of rats receiving lipopolysaccharide and treated with desmopressin was significantly reduced compared to lipopolysaccharide only group (LPS: 259±25.7 vs. LPS+DDAVP: 203±17.2; n/mm(2); p<0.05). Additionally, desmopressin treatment improved impaired intestinal microcirculation by improving functional capillary density following lipopolysaccharide administration in all examined layers of the intestinal wall. We also observed a significant decrease in TNF-α levels in rats which received desmopressin in endotoxemia compared to untreated rats (LPS: 383±64.2; LPS+DDAVP: 261.3±22; pg/ml; p<0.05).
  
  
  CONCLUSIONS
  Desmopressin administration improved intestinal capillary perfusion and reduced inflammatory response in rat endotoxemia.
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
authors.forename: K
authors.initials: K
authors.lastname: Wafa
authors.affiliation: Department of Anesthesia, Dalhousie University, Halifax, NS, Canada; Department of Microbiology and Immunology, Dalhousie University, Halifax, NS, Canada; Department of Pharmacology, Dalhousie University, Halifax, NS, Canada; Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany. Electronic address: chlehmann@dal.ca.
authors.forename: C
authors.initials: C
authors.lastname: Lehmann
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: L
authors.initials: L
authors.lastname: Wagner
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: I
authors.initials: I
authors.lastname: Drzymulski
authors.affiliation: Department of Anesthesiology and Intensive Care Medicine, Ernst Moritz Arndt University, Greifswald, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Wegner
authors.affiliation: Department of Pathophysiology, American School of Medicine, European University, Belgrade, Serbia.
authors.forename: D
authors.initials: D
authors.lastname: Pavlovic
mesh_terms: D000818:Animals; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D062186:Arterial Pressure / Q000187:drug effects; D001783:Blood Flow Velocity; D002196:Capillaries / Q000187:drug effects* / Q000503:physiopathology; D003894:Deamino Arginine Vasopressin / Q000494:pharmacology*; D004195:Disease Models, Animal; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D006339:Heart Rate / Q000187:drug effects; D018836:Inflammation Mediators / Q000097:blood; D007422:Intestines / Q000098:blood supply*; D036904:Leukocyte Rolling / Q000187:drug effects*; D007962:Leukocytes / Q000187:drug effects* / Q000276:immunology; D008070:Lipopolysaccharides; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D008856:Microscopy, Fluorescence; D018715:Microscopy, Video; D011917:Rats, Inbred Lew; D013152:Splanchnic Circulation / Q000187:drug effects*; D013997:Time Factors
chemical_list: D000893:Anti-Inflammatory Agents; D018836:Inflammation Mediators; D008070:Lipopolysaccharides; C433788:lipopolysaccharide, E. coli O26-B6; D003894:Deamino Arginine Vasopressin