title: Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.
abstract: We assessed the hypothesis that the epinephrine surge present during sepsis accelerates aerobic glycolysis and lactate production by increasing activity of skeletal muscle Na(+)-K(+)-ATPase. Healthy volunteers received an intravenous bolus of endotoxin or placebo in a randomized order on two different days. Endotoxemia induced a response resembling sepsis. Endotoxemia increased plasma epinephrine to a maximum at t = 2 h of 0.7 +/- 0.1 vs. 0.3 +/- 0.1 nmol/l (P < 0.05, n = 6-7). Endotoxemia reduced plasma K(+) reaching a nadir at t = 5 h of 3.3 +/- 0.1 vs. 3.8 +/- 0.1 mmol/l (P < 0.01, n = 6-7), followed by an increase to placebo level at t = 7-8 h. During the declining plasma K(+), a relative accumulation of K(+) was seen reaching a maximum at t = 6 h of 8.7 +/- 3.8 mmol/leg (P < 0.05). Plasma lactate increased to a maximum at t = 1 h of 2.5 +/- 0.5 vs. 0.9 +/- 0.1 mmol/l (P < 0.05, n = 8) in association with increased release of lactate from the legs. These changes were not associated with hypoperfusion or hypoxia. During the first 24 h after endotoxin infusion, renal K(+) excretion was 27 +/- 7 mmol, i.e., 58% higher than after placebo. Combination of the well-known stimulatory effect of catecholamines on skeletal muscle Na(+)-K(+)-ATPase activity, with the present confirmation of an expected Na(+)-K(+)- ATPase-induced decline in plasma K(+), suggests that the increased lactate release was due to increased Na(+)-K(+)-ATPase activity, supporting our hypothesis. Thus increased lactate levels in acutely and severely ill patients should not be managed only from the point of view that it reflects hypoxia.
authors.affiliation: Department of Medicine, University of Copenhagen, 2100 Copenhagen, Denmark. HenningBungaard@dadlnet.dk
authors.forename: Henning
authors.initials: H
authors.lastname: Bundgaard
authors.forename: Keld
authors.initials: K
authors.lastname: Kjeldsen
authors.forename: Karen
authors.initials: K
authors.lastname: Suarez Krabbe
authors.forename: Gerrit
authors.initials: G
authors.lastname: van Hall
authors.forename: Lene
authors.initials: L
authors.lastname: Simonsen
authors.forename: Jesper
authors.initials: J
authors.lastname: Qvist
authors.forename: Christian Muff
authors.initials: CM
authors.lastname: Hansen
authors.forename: Kirsten
authors.initials: K
authors.lastname: Moller
authors.forename: Lise
authors.initials: L
authors.lastname: Fonsmark
authors.forename: Per
authors.initials: P
authors.lastname: Lav Madsen
authors.forename: Bente
authors.initials: B
authors.lastname: Klarlund Pedersen
mesh_terms: D000328:Adult; D000332:Aerobiosis; D001132:Arm / Q000098:blood supply; D001158:Arteries / Q000503:physiopathology; D019446:Endotoxemia / Q000139:chemically induced / Q000378:metabolism*; D004731:Endotoxins; D004837:Epinephrine / Q000097:blood; D005334:Fever / Q000139:chemically induced; D006801:Humans; D007008:Hypokalemia / Q000139:chemically induced / Q000503:physiopathology; D007668:Kidney / Q000503:physiopathology; D019344:Lactic Acid / Q000097:blood*; D007866:Leg / Q000098:blood supply; D008070:Lipopolysaccharides; D018482:Muscle, Skeletal / Q000201:enzymology*; D011188:Potassium / Q000097:blood / Q000378:metabolism / Q000652:urine; D012016:Reference Values; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D014680:Veins / Q000503:physiopathology
chemical_list: D004731:Endotoxins; D008070:Lipopolysaccharides; D014409:Tumor Necrosis Factor-alpha; D019344:Lactic Acid; C044101:endotoxin, Escherichia coli; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D004837:Epinephrine