title: Effects of crystalloid and colloid resuscitation on hemorrhage-induced vascular hyporesponsiveness to norepinephrine in the rat.
abstract: BACKGROUND
  We have shown previously that hemorrhagic hypotension is associated with a progressive development of vascular hyporeactivity to norepinephrine (NE). The present study investigated whether select crystalloid or colloid resuscitation fluids would ameliorate this effect.
  
  
  METHODS
  Anesthetized male rats were hemorrhaged to and maintained at a mean arterial pressure (MAP) of 50 mm Hg for 60 minutes. Rats (n = 7 per group) were then resuscitated with lactated Ringer's (LR), 7.5% hypertonic saline (HS) for 1 hour followed by LR (HS-LR), Hespan, or Hextend to restore and maintain MAP to 70 mm Hg over 4 hours. Additional hemorrhaged groups were resuscitated with LR to the baseline MAP (LR-BL) or received no resuscitation. A sham hemorrhage group served as controls. The responses of MAP and the blood flow of the superior mesenteric, celiac, left renal, and left femoral arteries to NE (3 microg/kg administered intravenously) were measured at BL (prehemorrhage); at the end of the hypotensive period; and at 1, 2, and 4 hours after resuscitation.
  
  
  RESULTS
  Hemorrhagic hypotension significantly (p < 0.01) reduced the NE-induced pressor response in MAP and significantly reduced the contractile responses (reflected by the reduction of blood flow after NE administration) of the four arteries to NE. Hespan and Hextend infusion improved the NE response of MAP and the contractile responses of the observed arteries to NE significantly better than LR, HS-LR, or LR-BL. The colloids improved the vascular contractile responses to NE in the superior mesenteric and left femoral arteries and the pressor response of MAP to NE, to 80% to 90% of their basal response level compared with 40% to 60% with the crystalloid fluids (p < 0.05). LR-BL infusion resulted in hemodilution, with no added benefit to vascular responsiveness.
  
  
  CONCLUSIONS
  These data suggest that hypotensive resuscitation to 70 mm Hg with colloids was better than crystalloids in improving vascular responsiveness to the pressor effects of NE and required smaller volumes. Normotensive resuscitation with LR was not better than hypotensive resuscitation. Not all vasculatures improved equally after fluid resuscitation.
authors.affiliation: U.S. Army Institute of Surgical Research, Fort Sam Houston, Texas 78234-6315, USA.
authors.forename: Liang-Ming
authors.initials: LM
authors.lastname: Liu
authors.forename: John A
authors.initials: JA
authors.lastname: Ward
authors.forename: Michael A
authors.initials: MA
authors.lastname: Dubick
mesh_terms: D000818:Animals; D001794:Blood Pressure / Q000187:drug effects / Q000502:physiology; D003102:Colloids / Q000494:pharmacology* / Q000627:therapeutic use*; D000077324:Crystalloid Solutions; D004195:Disease Models, Animal; D005440:Fluid Therapy; D006470:Hemorrhage / Q000150:complications* / Q000503:physiopathology / Q000628:therapy*; D006895:Hydroxyethyl Starch Derivatives / Q000494:pharmacology* / Q000627:therapeutic use*; D007022:Hypotension / Q000209:etiology* / Q000503:physiopathology / Q000628:therapy*; D007552:Isotonic Solutions / Q000494:pharmacology* / Q000627:therapeutic use*; D008297:Male; D009131:Muscle, Smooth, Vascular / Q000187:drug effects / Q000503:physiopathology; D009638:Norepinephrine / Q000494:pharmacology*; D010952:Plasma Substitutes / Q000494:pharmacology* / Q000627:therapeutic use*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects / Q000502:physiology; D012151:Resuscitation; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic / Q000494:pharmacology* / Q000627:therapeutic use*; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D003102:Colloids; D000077324:Crystalloid Solutions; D006895:Hydroxyethyl Starch Derivatives; D007552:Isotonic Solutions; D010952:Plasma Substitutes; D000077325:Ringer's Lactate; D012462:Saline Solution, Hypertonic; D014662:Vasoconstrictor Agents; D009638:Norepinephrine