title: Ethyl pyruvate improves systemic and hepatosplanchnic hemodynamics and prevents lipid peroxidation in a porcine model of resuscitated hyperdynamic endotoxemia.
abstract: OBJECTIVE
  To investigate the systemic, pulmonary, and hepatosplanchnic hemodynamic and metabolic effects of delayed treatment with ethyl pyruvate in a long-term porcine model of hyperdynamic endotoxemia.
  
  
  METHODS
  Prospective, randomized, controlled experimental study with repeated measures.
  
  
  METHODS
  Investigational animal laboratory.
  
  
  METHODS
  Anesthetized, mechanically ventilated, and instrumented pigs.
  
  
  METHODS
  After 12 hrs of continuous infusion of lipopolysaccharide and hydroxyethyl starch to keep mean arterial pressure >60 mm Hg, swine randomly received placebo (Ringer's solution; control group, n = 11) or ethyl pyruvate in lactated Ringer's solution (n = 8; 0.03 g.kg(-1) loading dose over 10 mins, thereafter 0.03 g.kg(-1)hr(-1) for 12 hrs).
  
  
  RESULTS
  Whereas mean arterial pressure significantly decreased in control animals, mean arterial pressure was maintained at the baseline level in pigs treated with ethyl pyruvate. Global oxygen uptake was comparable, so that the trend toward a higher oxygen transport and the significantly higher mixed venous hemoglobin oxygen saturation resulted in a significantly lower oxygen extraction in the ethyl pyruvate group. Ethyl pyruvate reduced intrapulmonary venous admixture and resulted in significantly greater Pa(O2)/F(IO2) ratios. Despite comparable urine production in the two groups during the first 18 hrs of endotoxemia, ethyl pyruvate significantly increased diuresis during the last 6 hrs of the study. Lipopolysaccharide-induced systemic and regional venous metabolic acidosis was significantly ameliorated by ethyl pyruvate. Endotoxemia increased both blood nitrate + nitrite and isoprostane concentrations, and ethyl pyruvate attenuated the response of these markers of nitric oxide production and lipid peroxidation.
  
  
  CONCLUSIONS
  Ethyl pyruvate infusion resulted in improved hemodynamic stability and ameliorated acid-base derangements induced by chronic endotoxemia in pigs. Reduced oxidative stress and an decreased nitric oxide release probably contributed to these effects.
authors.affiliation: Sektion Anästhesiologische Pathophysiologie und Verfahrensentwicklung, Universitätsklinikum, Ulm, Germany.
authors.forename: Balázs
authors.initials: B
authors.lastname: Hauser
authors.forename: Jochen
authors.initials: J
authors.lastname: Kick
authors.forename: Pierre
authors.initials: P
authors.lastname: Asfar
authors.forename: Ulrich
authors.initials: U
authors.lastname: Ehrmann
authors.forename: Maura
authors.initials: M
authors.lastname: Albicini
authors.forename: Josef
authors.initials: J
authors.lastname: Vogt
authors.forename: Ulrich
authors.initials: U
authors.lastname: Wachter
authors.forename: Uwe Bernd
authors.initials: UB
authors.lastname: Brückner
authors.forename: Mitchell P
authors.initials: MP
authors.lastname: Fink
authors.forename: Peter
authors.initials: P
authors.lastname: Radermacher
authors.forename: Hendrik
authors.initials: H
authors.lastname: Bracht
mesh_terms: D000138:Acidosis / Q000188:drug therapy; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D004195:Disease Models, Animal; D004231:Diuresis / Q000187:drug effects; D019446:Endotoxemia / Q000097:blood / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology*; D006439:Hemodynamics / Q000187:drug effects*; D015227:Lipid Peroxidation / Q000187:drug effects*; D008070:Lipopolysaccharides / Q000008:administration & dosage; D008102:Liver Circulation / Q000187:drug effects*; D009566:Nitrates / Q000097:blood; D009573:Nitrites / Q000097:blood; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption / Q000187:drug effects; D011446:Prospective Studies; D011652:Pulmonary Circulation / Q000187:drug effects; D011773:Pyruvates / Q000008:administration & dosage / Q000627:therapeutic use*; D011897:Random Allocation; D012121:Respiration, Artificial; D012151:Resuscitation; D013152:Splanchnic Circulation / Q000187:drug effects*; D013552:Swine
chemical_list: D008070:Lipopolysaccharides; D009566:Nitrates; D009573:Nitrites; D011773:Pyruvates; C046522:ethyl pyruvate; D010100:Oxygen