title: Small intestinal production of nitric oxide is decreased following resuscitated hemorrhage.
abstract: BACKGROUND
  Small intestine microvascular vasoconstriction and hypoperfusion develop after resuscitation (RES) from hemorrhage (HEM), despite restoration of central hemodynamics. The responsible mechanisms are unclear. We hypothesized that the microvascular impairment following HEM/RES was due to decreased intestinal microvascular nitric oxide (NO) production.
  
  
  METHODS
  Male Sprague-Dawley rats (195-230 g) were utilized and three experimental groups were studied: (1) SHAM (cannulated but no HEM), (2) HEM only, and (3) HEM/RES. HEM was to 50% of baseline mean arterial pressure for 60 min, and RES was with shed blood and an equivalent volume of saline. Ex vivo isolated intestinal perfusion and a fluorometric modification of the Greiss reaction were used to quantify production of NO metabolites (NOx). Perfusate von Willebrand factor (vWF) was used as an indirect marker of endothelial cell activation or injury. To assess the degree of NO scavenging by oxygen-derived free radicals, immunohistochemistry was used to detect nitrotyrosine formation in the intestine.
  
  
  RESULTS
  Intestinal NOx decreased following HEM/RES (SHAM 1.35 +/- 0.2 mM vs HEM/RES 0.60 +/- 0.1 mM, P < 0.05), but not with HEM alone (1.09 +/- 0.3 mM). There were no differences in serum NOx levels between the three groups. Release of vWF was increased during the HEM period (SHAM 0.18 +/- 0.1 g/dl vs HEM 1.66 +/- 0.6 g/dl, P < 0.05). There was no detectable nitrotyrosine formation in any group.
  
  
  CONCLUSIONS
  Intestinal NO metabolites decrease following HEM/RES. Elevated vWF levels during HEM and the lack of detectable nitrotyrosine suggest that this is due to decreased endothelial cell production of NO. HEM/RES-induced endothelial cell dysfunction may contribute to persistent small intestine post-RES hypoperfusion and vasoconstriction.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Louisville, Kentucky, 40292, USA.
authors.forename: T M
authors.initials: TM
authors.lastname: Fruchterman
authors.forename: D A
authors.initials: DA
authors.lastname: Spain
authors.forename: P J
authors.initials: PJ
authors.lastname: Matheson
authors.forename: A W
authors.initials: AW
authors.lastname: Martin
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: P D
authors.initials: PD
authors.lastname: Harris
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D006471:Gastrointestinal Hemorrhage / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006439:Hemodynamics / Q000502:physiology; D007150:Immunohistochemistry; D007421:Intestine, Small / Q000378:metabolism* / Q000473:pathology; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D014841:von Willebrand Factor / Q000032:analysis
chemical_list: D014841:von Willebrand Factor; D009569:Nitric Oxide