title: Heparan preserves intestinal perfusion after hemorrhage and resuscitation.
abstract: BACKGROUND
  Multiple system organ failure (MOF) remains a major source of morbidity and mortality in trauma patients. Despite restoration of central hemodynamics, intestinal hypoperfusion can persist. Mucosal ischemia and barrier breakdown are factors in the genesis of MOF. Heparan sulfate is a gycosaminoglycan similar to heparin, but with minimal anticoagulant properties. As an adjunct to resuscitation, it improves immunologic function and restores mucosal oxygenation and function. We hypothesized that resuscitation with heparan following hemorrhage wound prevents intestinal hypoperfusion.
  
  
  METHODS
  In vivo videomicroscopy was used to study small intestine microcirculation in rats. Animals were hemorrhaged to 50% of baseline mean arterial pressure (MAP) and maintained there. Resuscitation was initiated when the return of 10% shed blood was required to keep MAP at 50%. Animals received either heparan (7 mg/kg/1 ml saline) or saline (1 ml) followed by the remaining shed blood and an equal volume of saline. MAP, cardiac output (CO), A1 arteriole diameters, and flow were determined.
  
  
  RESULTS
  Resuscitation of the saline control group resulted in normal MAP with elevation of CO to 25-40% above baseline. The heparan group had return of MAP but only a moderate increase in CO (7-15%). Saline resuscitation led to progressive deterioration in A1 diameters and flow. The addition of heparan prevented delayed A1 constriction and significantly improved perfusion.
  
  
  CONCLUSIONS
  Heparan prior to resuscitation improved intestinal perfusion, despite a relative reduction in CO. Improvement in nutrient blood flow may protect the mucosal barrier, reducing the incidence of MOF, and suggests that heparan may be useful in resuscitation of trauma patients.
authors.affiliation: Department of Surgery, University of Louisville School of Medicine, Kentucky 40292, USA.
authors.forename: J M
authors.initials: JM
authors.lastname: Watkins
authors.forename: D A
authors.initials: DA
authors.lastname: Spain
authors.forename: R J
authors.initials: RJ
authors.lastname: Krysztopik
authors.forename: P J
authors.initials: PJ
authors.lastname: Downard
authors.forename: M A
authors.initials: MA
authors.lastname: Wilson
authors.forename: R N
authors.initials: RN
authors.lastname: Garrison
mesh_terms: D000818:Animals; D006439:Hemodynamics / Q000187:drug effects; D006497:Heparan Sulfate / Q000494:pharmacology*; D007422:Intestines / Q000098:blood supply*; D008297:Male; D008833:Microcirculation / Q000187:drug effects; D009102:Multiple Organ Failure / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation; D012771:Shock, Hemorrhagic / Q000503:physiopathology; D014741:Video Recording
chemical_list: D006497:Heparan Sulfate