title: Effects of endotoxin on lactate metabolism in humans.
abstract: BACKGROUND
  Hyperlactatemia represents one prominent component of the metabolic response to sepsis. In critically ill patients, hyperlactatemia is related to the severity of the underlying condition. Both an increased production and a decreased utilization and clearance might be involved in this process, but their relative contribution remains unknown. The present study aimed at assessing systemic and muscle lactate production and systemic lactate clearance in healthy human volunteers, using intravenous endotoxin (LPS) challenge.
  
  
  METHODS
  Fourteen healthy male volunteers were enrolled in 2 consecutive studies (n = 6 in trial 1 and n = 8 in trial 2). Each subject took part in one of two investigation days (LPS-day with endotoxin injection and placebo-day with saline injection) separated by one week at least and in a random order. In trial 1, their muscle lactate metabolism was monitored using microdialysis. In trial 2, their systemic lactate metabolism was monitored by means of a constant infusion of exogenous lactate. Energy metabolism was monitored by indirect calorimetry and glucose kinetics was measured with 6,6-H2 glucose.
  
  
  RESULTS
  In both trials, LPS increased energy expenditure (p = 0.011), lipid oxidation (p<0.0001), and plasma lactate concentration (p = 0.016). In trial 1, lactate concentration in the muscle microdialysate was higher than in blood, indicating lactate production by muscles. This was, however, similar with and without LPS. In trial 2, calculated systemic lactate production increased after LPS (p = 0.031), while lactate clearance remained unchanged.
  
  
  CONCLUSIONS
  LPS administration increases lactatemia by increasing lactate production rather than by decreasing lactate clearance. Muscle is, however, unlikely to be a major contributor to this increase in lactate production.
  
  
  BACKGROUND
  ClinicalTrials.gov NCT01647997.
authors: Burkhard
authors: B
authors: Michaeli
authors: Alexandre
authors: A
authors: Martinez
authors: Jean-Pierre
authors: JP
authors: Revelly
authors: Marie-Christine
authors: MC
authors: Cayeux
authors: René L
authors: RL
authors: Chioléro
authors: Luc
authors: L
authors: Tappy
authors: Mette M
authors: MM
authors: Berger
mesh_terms: D000293:Adolescent; D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D002153:Calorimetry, Indirect; D004731:Endotoxins / Q000494:pharmacology*; D004734:Energy Metabolism; D064368:Healthy Volunteers; D006801:Humans; D007773:Lactates / Q000378:metabolism*; D050356:Lipid Metabolism; D008297:Male; D017551:Microdialysis; D018482:Muscle, Skeletal / Q000378:metabolism*; D018805:Sepsis / Q000378:metabolism
chemical_list: D001786:Blood Glucose; D004731:Endotoxins; D007773:Lactates