Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.

Henning Bundgaard; Keld Kjeldsen; Karen Suarez Krabbe; Gerrit van Hall; Lene Simonsen; Jesper Qvist; Christian Muff Hansen; Kirsten Moller; Lise Fonsmark; Per Lav Madsen; Bente Klarlund Pedersen

doi:10.1152/ajpheart.00639.2002

Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.

Henning Bundgaard, Keld Kjeldsen, Karen Suarez Krabbe, Gerrit van Hall, Lene Simonsen, Jesper Qvist, Christian Muff Hansen, Kirsten Moller, Lise Fonsmark, Per Lav Madsen, Bente Klarlund Pedersen

Exercise and Muscle

57 Citations (Scopus)

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.

Original language	English
Journal	American Journal of Physiology: Heart and Circulatory Physiology
Volume	284
Issue number	3
Pages (from-to)	H1028-34
ISSN	0363-6135
DOIs	https://doi.org/10.1152/ajpheart.00639.2002
Publication status	Published - 2002

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Bundgaard, H., Kjeldsen, K., Suarez Krabbe, K., van Hall, G., Simonsen, L., Qvist, J., Hansen, C. M., Moller, K., Fonsmark, L., Lav Madsen, P., & Klarlund Pedersen, B. (2002). Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans. American Journal of Physiology: Heart and Circulatory Physiology, 284(3), H1028-34. https://doi.org/10.1152/ajpheart.00639.2002

Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans. / Bundgaard, Henning; Kjeldsen, Keld; Suarez Krabbe, Karen et al.

In: American Journal of Physiology: Heart and Circulatory Physiology, Vol. 284, No. 3, 2002, p. H1028-34.

Research output: Contribution to journal › Journal article › Research › peer-review

Bundgaard, H, Kjeldsen, K, Suarez Krabbe, K, van Hall, G, Simonsen, L, Qvist, J, Hansen, CM, Moller, K, Fonsmark, L, Lav Madsen, P & Klarlund Pedersen, B 2002, 'Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.', American Journal of Physiology: Heart and Circulatory Physiology, vol. 284, no. 3, pp. H1028-34. https://doi.org/10.1152/ajpheart.00639.2002

@article{07e25b50ac0211ddb5e9000ea68e967b,

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.",

author = "Henning Bundgaard and Keld Kjeldsen and {Suarez Krabbe}, Karen and {van Hall}, Gerrit and Lene Simonsen and Jesper Qvist and Hansen, {Christian Muff} and Kirsten Moller and Lise Fonsmark and {Lav Madsen}, Per and {Klarlund Pedersen}, Bente",

note = "Keywords: Adult; Aerobiosis; Arm; Arteries; Endotoxemia; Endotoxins; Epinephrine; Fever; Humans; Hypokalemia; Kidney; Lactic Acid; Leg; Lipopolysaccharides; Muscle, Skeletal; Potassium; Reference Values; Sodium-Potassium-Exchanging ATPase; Tumor Necrosis Factor-alpha; Veins",

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doi = "10.1152/ajpheart.00639.2002",

language = "English",

volume = "284",

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T1 - Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.

AU - Bundgaard, Henning

AU - Kjeldsen, Keld

AU - Suarez Krabbe, Karen

AU - van Hall, Gerrit

AU - Simonsen, Lene

AU - Qvist, Jesper

AU - Hansen, Christian Muff

AU - Moller, Kirsten

AU - Fonsmark, Lise

AU - Lav Madsen, Per

AU - Klarlund Pedersen, Bente

N1 - Keywords: Adult; Aerobiosis; Arm; Arteries; Endotoxemia; Endotoxins; Epinephrine; Fever; Humans; Hypokalemia; Kidney; Lactic Acid; Leg; Lipopolysaccharides; Muscle, Skeletal; Potassium; Reference Values; Sodium-Potassium-Exchanging ATPase; Tumor Necrosis Factor-alpha; Veins

PY - 2002

Y1 - 2002

N2 - 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.

AB - 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.

U2 - 10.1152/ajpheart.00639.2002

DO - 10.1152/ajpheart.00639.2002

M3 - Journal article

C2 - 12446281

SN - 0363-6135

VL - 284

SP - H1028-34

JO - American Journal of Physiology - Heart and Circulatory Physiology

JF - American Journal of Physiology - Heart and Circulatory Physiology

IS - 3

ER -

Endotoxemia stimulates skeletal muscle Na+-K+-ATPase and raises blood lactate under aerobic conditions in humans.

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