title: Myocardial lactate deprivation is associated with decreased cardiovascular performance, decreased myocardial energetics, and early death in endotoxic shock.
abstract: OBJECTIVE
  We examined whether lactate availability is a limiting factor for heart function during endotoxic shock, and whether lactate deprivation thus induces heart energy depletion, thereby altering cardiovascular performance. The study goals were to determine whether muscle lactate production is linked to beta(2)-stimulation and to ascertain the effects of systemic lactate deprivation on hemodynamics, lactate metabolism, heart energetics, and outcome in a lethal model of rat's endotoxic shock.
  
  
  METHODS
  We modulated the adrenergic pathway in skeletal muscle using microdialysis with ICI-118551, a selective beta(2)-blocker. Muscle lactate formation in endotoxic shock was further inhibited by intravenous infusion of ICI-118551 or dichloroacetate (DCA), an activator of pyruvate dehydrogenase (DCA) and their combination.
  
  
  RESULTS
  Muscle lactate formation was decreased by ICI-118551. During endotoxic shock both ICI-118151 and DCA decreased circulating and heart lactate concentrations in parallel with a decrease in tissue ATP content. The combination ICI-118551-DCA resulted in early cardiovascular collapse and death. The addition of molar lactate to ICI-1185111 plus DCA blunted the effects of ICI-118551+DCA on hemodynamics. Survival was markedly less with ICI-118551 than with endotoxin alone.
  
  
  CONCLUSIONS
  Systemic lactate deprivation is detrimental to myocardial energetics, cardiovascular performance, and outcome.
authors.affiliation: Coordination Circulation UHP-INSERM, Groupe CHOC, Faculté de Médecine, Université Henri Poincaré Nancy 1, Nancy, France. b.levy@chu-nancy.fr
authors.forename: Bruno
authors.initials: B
authors.lastname: Levy
authors.forename: Arnauld
authors.initials: A
authors.lastname: Mansart
authors.forename: Chantal
authors.initials: C
authors.lastname: Montemont
authors.forename: Sebastien
authors.initials: S
authors.lastname: Gibot
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Mallie
authors.forename: Veronique
authors.initials: V
authors.lastname: Regnault
authors.forename: Thomas
authors.initials: T
authors.lastname: Lecompte
authors.forename: Patrick
authors.initials: P
authors.lastname: Lacolley
mesh_terms: D000704:Analysis of Variance; D000818:Animals; D003326:Coronary Circulation; D004734:Energy Metabolism; D004837:Epinephrine / Q000378:metabolism; D006019:Glycolysis; D000860:Hypoxia / Q000378:metabolism; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D018343:Receptors, Adrenergic, beta-2 / Q000378:metabolism; D012772:Shock, Septic / Q000378:metabolism / Q000503:physiopathology*; D016019:Survival Analysis
chemical_list: D018343:Receptors, Adrenergic, beta-2; D019344:Lactic Acid; D004837:Epinephrine