Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.
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.
Bundgaard
Henning
H
Department of Medicine, University of Copenhagen, 2100 Copenhagen, Denmark. HenningBungaard@dadlnet.dk
Kjeldsen
Keld
K
Suarez Krabbe
Karen
K
van Hall
Gerrit
G
Simonsen
Lene
L
Qvist
Jesper
J
Hansen
Christian Muff
CM
Moller
Kirsten
K
Fonsmark
Lise
L
Lav Madsen
Per
P
Klarlund Pedersen
Bente
B
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
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