Role of skeletal muscle Na+-K+ ATPase activity in increased lactate production in sub-acute sepsis.
Bacterial sepsis is frequently accompanied by increased blood concentration of lactic acid, which traditionally is attributed to poor tissue perfusion, hypoxia and anaerobic glycolysis. Therapy aimed at improving oxygen delivery to tissues often does not correct the hyperlactatemia, suggesting that high blood lactate in sepsis is not due to hypoxia. Various tissues, including skeletal muscle, demonstrate increased lactate production under well-oxygenated conditions when the activity of the Na+-K+ ATPase is stimulated. Although both muscle Na+-K+ ATPase activity and muscle plasma membrane content of Na+, K+-ATPase subunits are increased in sepsis, no studies in vivo have demonstrated correlation between lactate production and changes in intracellular Na+ and K+ resulting from increased Na+-K+ pump activity in sepsis. Plasma concentrations of lactate and epinephrine, a known stimulator of the Na+-K+ pump, were increased in rats made septic by E. coli injection. Muscle lactate content was significantly increased in septic rats, although muscle ATP and phosphocreatine remained normal, suggesting oxygen delivery remained adequate for mitochondrial energy metabolism. In septic rats, muscle intracellular ratio of Na+:K+ was significantly reduced, indicating increased Na+-K+ pump activity. These data thus demonstrate that increased muscle lactate during sepsis correlates with evidence of elevated muscle Na+-K+ ATPase activity, but not with evidence of impaired oxidative metabolism. This study also further supports a role for epinephrine in this process.
McCarter
Freda D
FD
Department of Surgery, University of Cincinnati College of Medicine, Ohio 45267, USA.
Nierman
S Renee
SR
James
J Howard
JH
Wang
Li
L
King
Jy-Kung
JK
Friend
Lou Ann
LA
Fischer
Josef E
JE
D000255:Adenosine Triphosphate / Q000378:metabolism; D000818:Animals; D004837:Epinephrine / Q000097:blood; D019344:Lactic Acid / Q000378:metabolism*; D008297:Male; D018482:Muscle, Skeletal / Q000201:enzymology*; D010725:Phosphocreatine / Q000378:metabolism; D011188:Potassium / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000378:metabolism*; D012964:Sodium / Q000032:analysis; D000254:Sodium-Potassium-Exchanging ATPase / Q000502:physiology*
D010725:Phosphocreatine; D019344:Lactic Acid; D000255:Adenosine Triphosphate; D012964:Sodium; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium; D004837:Epinephrine