title: Effects of epinephrine and norepinephrine on hemodynamics, oxidative metabolism, and organ energetics in endotoxemic rats.
abstract: OBJECTIVE
  To determine whether epinephrine increases lactate concentration in sepsis through hypoxia or through a particular thermogenic or metabolic pathway.
  
  
  METHODS
  Prospective, controlled experimental study in rats.
  
  
  METHODS
  Experimental laboratory in a university teaching hospital.
  
  
  METHODS
  Three groups of anesthetized, mechanically ventilated male Wistar rats received an intravenous infusion of 15 mg/kg Escherichia coli O127:B8 endotoxin. Rats were treated after 90 min by epinephrine ( n=14), norepinephrine ( n=14), or hydroxyethyl starch ( n=14). Three groups of six rats served as time-matched control groups and received saline, epinephrine, or norepinephrine from 90 to 180 degrees min. Mean arterial pressure, aortic, renal, mesenteric and femoral blood flow, arterial blood gases, lactate, pyruvate, and nitrate were measured at baseline and 90 and 180 min after endotoxin challenge. At the end of experiments biopsy samples were taken from the liver, heart, muscle, kidney, and small intestine for tissue adenine nucleotide and lactate/pyruvate measurements.
  
  
  RESULTS
  Endotoxin induced a decrease in mean arterial pressure and in aortic, mesenteric, and renal blood flow. Plasmatic and tissue lactate increased with a high lactate/pyruvate (L/P) ratio. ATP decreased in liver, kidney, and heart. The ATP/ADP ratio did not change, and phosphocreatinine decreased in all organs. Epinephrine and norepinephrine increased mean arterial pressure to baseline values. Epinephrine increased aortic blood flow while renal blood low decreased with both drugs. Plasmatic lactate increased with a stable L/P ratio with epinephrine and did not change with norepinephrine compared to endotoxin values. Nevertheless epinephrine and norepinephrine when compared to endotoxin values did not change tissue L/P ratios or ATP concentration in muscle, heart, gut, or liver. In kidney both drugs decreased ATP concentration.
  
  
  CONCLUSIONS
  Our data demonstrate in a rat model of endotoxemia that epinephrine-induced hyperlactatemia is not related to cellular hypoxia.
authors.affiliation: Réanimation Médicale, Hôpital Central, 54035, Nancy Cedex, France. b.levy@chu-nancy.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
authors.forename: Arnaud
authors.initials: A
authors.lastname: Mansart
authors.forename: Pierre-Edouard
authors.initials: PE
authors.lastname: Bollaert
authors.forename: Patricia
authors.initials: P
authors.lastname: Franck
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mallie
mesh_terms: D000140:Acidosis, Lactic / Q000378:metabolism / Q000382:microbiology / Q000503:physiopathology; D000244:Adenosine Diphosphate / Q000032:analysis; D000255:Adenosine Triphosphate / Q000032:analysis; D000818:Animals; D001784:Blood Gas Analysis; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D019446:Endotoxemia / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D004734:Energy Metabolism / Q000187:drug effects*; D004837:Epinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D004927:Escherichia coli Infections / Q000150:complications / Q000188:drug therapy* / Q000378:metabolism / Q000503:physiopathology; D006019:Glycolysis / Q000187:drug effects; D006439:Hemodynamics / Q000187:drug effects*; D006801:Humans; D007668:Kidney / Q000737:chemistry; D019344:Lactic Acid / Q000032:analysis / Q000097:blood; D008099:Liver / Q000737:chemistry; D009206:Myocardium / Q000737:chemistry; D009566:Nitrates / Q000032:analysis; D009638:Norepinephrine / Q000494:pharmacology / Q000627:therapeutic use*; D010725:Phosphocreatine / Q000031:analogs & derivatives* / Q000032:analysis; D011773:Pyruvates / Q000032:analysis / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D014018:Tissue Distribution
chemical_list: D009566:Nitrates; D011773:Pyruvates; D010725:Phosphocreatine; D019344:Lactic Acid; C025403:phosphocreatinine; D000244:Adenosine Diphosphate; D000255:Adenosine Triphosphate; D009638:Norepinephrine; D004837:Epinephrine