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Desmopressin improves intestinal functional capillary density and decreases leucocyte activation in experimental endotoxemia.
MedLine Citation:
PMID:  24035754     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
BACKGROUND: Blood flow to the intestine is decreased in sepsis in favour 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 analogue 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 leucocytes 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).
CONCLUSION: Desmopressin administration improved intestinal capillary perfusion and reduced inflammatory response in rat endotoxemia.
Authors:
K Wafa; C Lehmann; L Wagner; I Drzymulski; A Wegner; D Pavlovic
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2013-9-12
Journal Detail:
Title:  Microvascular research     Volume:  -     ISSN:  1095-9319     ISO Abbreviation:  Microvasc. Res.     Publication Date:  2013 Sep 
Date Detail:
Created Date:  2013-9-16     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  0165035     Medline TA:  Microvasc Res     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
© 2013.
Affiliation:
Department of Anesthesia, Dalhousie University, Halifax, NS, Canada.
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