Endotoxin-induced hyperlactatemia results from decreased lactate clearance in hemodynamically stable rats. Crit Care Med 2002 Nov;30(11):2509-14
Date
11/21/2002Pubmed ID
12441762DOI
10.1097/00003246-200211000-00017Scopus ID
2-s2.0-0036852909 (requires institutional sign-in at Scopus site) 20 CitationsAbstract
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).
DESIGN: Prospective, controlled trial.
SETTING: Research laboratory in a university hospital.
SUBJECTS: Male Sprague-Dawley rats weighing 275-425 g with chronic vascular catheters.
INTERVENTIONS: 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.
MEASUREMENTS AND MAIN 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.
Author List
Severin PN, Uhing MR, Beno DW, Kimura REAuthor
Michael R. Uhing MD Professor in the Pediatrics department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Acidosis, LacticAnalysis of Variance
Animals
Hemodynamics
Lactates
Lipopolysaccharides
Liver
Male
Prospective Studies
Rats
Rats, Sprague-Dawley
Sepsis
Splanchnic Circulation