Desmopressin improves intestinal functional capillary density and decreases leukocyte activation in experimental endotoxemia

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 (1 mu g/kg/ml), lipopolysaccharide (5 mg/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, nonfunctional 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-alpha 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). Conclusion: Desmopressin administration improved intestinal capillary perfusion and reduced inflammatory response in rat endotoxemia. (C) 2013 Published by Elsevier Inc.