title: Endotoxin-induced hyperlactatemia results from decreased lactate clearance in hemodynamically stable rats.
abstract: OBJECTIVE
  To determine whether endotoxin-induced hyperlactatemia in hemodynamically stable animals is due to increased lactate production or decreased lactate clearance by measuring lactate turnover rate in the vascular compartment (LTRvc).
  
  
  METHODS
  Prospective, controlled trial.
  
  
  METHODS
  Research laboratory in a university hospital.
  
  
  METHODS
  Male Sprague-Dawley rats weighing 275-425 g with chronic vascular catheters.
  
  
  METHODS
  Chronically catheterized rats were treated with 6 microg/kg endotoxin or saline. LTRvc was determined from the specific activity of carbon-14 [14C]lactate in aortic blood during a constant infusion of [14C]lactate into the inferior vena cava. The role of the splanchnic organs in lipopolysaccharide-induced alterations in LTRvc was determined from the splanchnic first-pass clearance of [14C]lactate infused into the superior mesenteric artery and direct measurements of blood lactate concentration gradients across the splanchnic organs.
  
  
  RESULTS
  Despite a 260% increase in lactate concentrations after lipopolysaccharide treatment, the specific activity of [14C]lactate and the LTRvc did not change, indicating that lipopolysaccharide-induced hyperlactatemia is caused by decreased lactate clearance from the vascular compartment rather than increased lactate flux into the vascular compartment. In contrast, lactate clearance by the splanchnic system was increased. The specific activity of [14C]lactate in aortic blood decreased 33% after lipopolysaccharide treatment when the [14C]lactate was infused into the superior mesenteric artery, indicating increased first-pass clearance of [14C]lactate by the splanchnic organs. Furthermore, the hepatic venous-aortic concentration gradient of lactate became increasingly negative after lipopolysaccharide treatment, indicating increased vascular extraction of lactate by the splanchnic system (0.07 +/- 0.07 micromol/mL vs. -0.34 +/- 0.14 micromol/mL).
  
  
  CONCLUSIONS
  Lipopolysaccharide-induced hyperlactatemia in hemodynamically stable rats is caused by a net decrease in lactate clearance from the vascular compartment despite the fact that the clearance of lactate by the splanchnic system remains intact.
authors.affiliation: Division of Critical Care, Department of Pediatrics, Rush-Presbyterian-St. Luke's Medical Center, Chicago, IL, USA.
authors.forename: Paul N
authors.initials: PN
authors.lastname: Severin
authors.forename: Michael R
authors.initials: MR
authors.lastname: Uhing
authors.forename: David W A
authors.initials: DW
authors.lastname: Beno
authors.forename: Robert E
authors.initials: RE
authors.lastname: Kimura
mesh_terms: D000140:Acidosis, Lactic / Q000097:blood / Q000209:etiology / Q000503:physiopathology*; D000704:Analysis of Variance; D000818:Animals; D006439:Hemodynamics; D007773:Lactates / Q000097:blood*; D008070:Lipopolysaccharides; D008099:Liver / Q000378:metabolism; D008297:Male; D011446:Prospective Studies; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000097:blood / Q000150:complications / Q000503:physiopathology*; D013152:Splanchnic Circulation / Q000502:physiology
chemical_list: D007773:Lactates; D008070:Lipopolysaccharides