title: Hypoxia is not the sole cause of lactate production during shock.
abstract: BACKGROUND
  Traditionally, elevated blood lactate after hemorrhage is interpreted as tissue hypoperfusion, hypoxia, and anaerobic glycolysis. The severity and duration of the increase in blood lactate correlate with death. Recent in vitro studies indicate that epinephrine stimulates lactate production in well-oxygenated skeletal muscle by increasing activity of the Na+-K+-adenosine triphosphatase (ATPase), which derives a significant amount of adenosine triphosphate from glycolysis. Using in vivo microdialysis, we tested whether inhibiting the Na+-K+ pump with ouabain could reduce muscle lactate production during local exposure, via the microdialysis probe, to epinephrine or during hemorrhage in rats.
  
  
  METHODS
  Microdialysis catheters were placed in the muscle of both thighs of pentobarbital-anesthetized male Sprague-Dawley rats (275-350 g) and perfused (1 microL/min) with Krebs-phosphate buffer (pH 7.4) containing ethanol (5 mmol/L) to permit assessment of changes in local blood flow. To inhibit the Na+-K+-ATPase, ouabain (2-3 mmol/L) was added to the perfusate of one leg. In one series of studies, epinephrine was added to the perfusate. In another series, rats were hemorrhaged to a mean arterial pressure of 45 mm Hg for 30 minutes, followed by resuscitation with shed blood and 0.9% sodium chloride. Dialysate fractions were analyzed for lactate and ethanol fluorometrically.
  
  
  RESULTS
  Lactate rose during epinephrine exposure or during hemorrhage and resuscitation. Treatment with ouabain reduced dialysate lactate concentration significantly in both series of studies. Local blood flow was reduced by either epinephrine or hemorrhage, but returned toward baseline afterward. Ouabain had no apparent effect on local blood flow.
  
  
  CONCLUSIONS
  Increased Na+-K+ATPase activity during epinephrine treatment or hemorrhage contributes to muscle lactate production. Hypoxia is not necessarily the sole cause of hyperlactatemia during and after hemorrhagic shock.
authors.affiliation: Department of Surgery, University of Cincinnati College of Medicine, and Shriners Hospital for Children, Shriners Burns Hospital, Cincinnati, Ohio, USA.
authors.forename: Fred A
authors.initials: FA
authors.lastname: Luchette
authors.forename: W Andrew
authors.initials: WA
authors.lastname: Jenkins
authors.forename: Lou Ann
authors.initials: LA
authors.lastname: Friend
authors.forename: Chunhua
authors.initials: C
authors.lastname: Su
authors.forename: Josef E
authors.initials: JE
authors.lastname: Fischer
authors.forename: J Howard
authors.initials: JH
authors.lastname: James
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D004837:Epinephrine / Q000494:pharmacology; D000431:Ethanol / Q000494:pharmacology; D000860:Hypoxia / Q000378:metabolism*; D019344:Lactic Acid / Q000096:biosynthesis* / Q000097:blood; D008297:Male; D017551:Microdialysis; D010042:Ouabain / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012039:Regional Blood Flow / Q000187:drug effects; D012771:Shock, Hemorrhagic / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*
chemical_list: D019344:Lactic Acid; D000431:Ethanol; D010042:Ouabain; D000254:Sodium-Potassium-Exchanging ATPase; D004837:Epinephrine