title: Nitric oxide involvement in the hemodynamic response to fluid resuscitation in endotoxic shock in rats.
abstract: OBJECTIVE
  Fluid loading is an essential part of cardiovascular resuscitation in septic shock. We hypothesized that fluid administration increases blood flow velocity and thus endothelial shear stress, causing the release of nitric oxide by the vascular endothelium. Because of endothelial dysfunction in sepsis, this mechanism would be less effective in septic animals. Fluid loading may have different effects in septic compared with control animals.
  
  
  METHODS
  Prospective, randomized, controlled study.
  
  
  METHODS
  Animal research laboratory.
  
  
  METHODS
  Male Sprague-Dawley rats.
  
  
  METHODS
  We tested the involvement of nitric oxide in the fluid-induced cardiovascular response after administration of lipopolysaccharide (5 mg/kg, n = 10) or vehicle (control, n = 10) in rats subsequently randomized after 165 mins to receive L-N(G)-nitroarginine (7.5 mg/kg) or saline (n = 5 in each group). At 180 mins, all animals received hydroxyethyl starch (fluid loading, 15 mL/kg in 15 mins). Reversal of L-N(G)-nitroarginine was studied with an intravenous bolus of L-arginine (300 mg/kg).
  
  
  RESULTS
  Lipopolysaccharide injection induced a hypokinetic shock (low blood pressure: -30% +/- 9%, p < .05), low cardiac output (aortic pulsed-Doppler probe: -20% +/- 8, p < .05), and unchanged systemic conductance, which turned into a hyperkinetic shock by fluid loading. Pretreatment with L-N(G)-nitroarginine totally abolished this fluid loading-induced vasodilation in control rats but only partially in lipopolysaccharide-treated rats, suggesting an altered endothelial response after lipopolysaccharide injection. Maximal aortic blood flow acceleration was used as an index of left ventricular systolic function. The improvement of maximal aortic blood flow acceleration observed during fluid loading in lipopolysaccharide-treated or control animals was blunted by L-N(G)-nitroarginine pretreatment, suggesting the involvement of nitric oxide in the myocardial response to fluid loading.
  
  
  CONCLUSIONS
  These results suggest that the endothelium participates in the hemodynamic response to fluid loading in control rats, but less in rats with septic shock, secondary to an altered nitric oxide-dependent vasodilation.
authors.affiliation: Laboratoire du Département d'Anesthésie-Réanimation, Centre Hospitalier Universitaire Lariboisière, Assistance Publique-Hôpitaux de Paris, Université Paris 7, France.
authors.forename: Marie-Reine
authors.initials: MR
authors.lastname: Losser
authors.forename: Anne-Pascale
authors.initials: AP
authors.lastname: Forget
authors.forename: Didier
authors.initials: D
authors.lastname: Payen
mesh_terms: D000818:Animals; D001011:Aorta / Q000503:physiopathology; D001783:Blood Flow Velocity / Q000187:drug effects; D002303:Cardiac Output, Low / Q000139:chemically induced; D004195:Disease Models, Animal; D004730:Endothelium, Vascular / Q000187:drug effects / Q000378:metabolism; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D004926:Escherichia coli; D007275:Injections, Intravenous; D008070:Lipopolysaccharides / Q000494:pharmacology*; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D019335:Nitroarginine / Q000494:pharmacology*; D011446:Prospective Studies; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D012151:Resuscitation / Q000379:methods*; D012772:Shock, Septic / Q000503:physiopathology*; D014664:Vasodilation / Q000187:drug effects / Q000502:physiology
chemical_list: D004791:Enzyme Inhibitors; D008070:Lipopolysaccharides; D019335:Nitroarginine; D009569:Nitric Oxide