title: Regional and systemic oxygen delivery/uptake relations and lactate flux in hyperdynamic, endotoxin-treated dogs.
abstract: Pathologic oxygen supply dependency (PO2SD) may be etiologic in multisystem organ failure (MSOF) and has been related to mortality in sepsis. Although elevated lactate levels are generally assumed to be a marker of anaerobiosis in these patients, endotoxin may increase serum lactate by inactivation of pyruvate dehydrogenase (PDH), unrelated to tissue PO2. We hypothesized that regional lactate flux may correlate poorly with local oxygen delivery in sepsis. This study examined both the whole-body (WB) and regional (isolated hind limb L and gut G) responses to endotoxin infusion in terms of oxygen delivery, oxygen uptake, and lactate flux in 12 pentobarbital-anesthetized dogs. To separate hypoxia-induced lactate production from that related to inactivation of PDH by endotoxin, half the dogs received dichloroacetate (DCA), a PDH activator. After endotoxin and volume resuscitation, each animal had low systemic vascular resistance with normal to high cardiac output. Despite adequate oxygen delivery to WB, L, and G, arterial lactate levels rose significantly. A 30-min hypoxic challenge (12% FIO2) did not increase lactate levels but did increase WB O2 uptake. DCA normalized lactate levels without influencing oxygen delivery and uptake relations. These data show that lactate levels in endotoxic states may be a poor marker of tissue hypoxia and may be more related to PDH activity.
authors.affiliation: Department of Pediatrics, University of Alabama, Birmingham 35294.
authors.forename: S E
authors.initials: SE
authors.lastname: Curtis
authors.forename: S M
authors.initials: SM
authors.lastname: Cain
mesh_terms: D000140:Acidosis, Lactic / Q000209:etiology / Q000378:metabolism; D000818:Animals; D002302:Cardiac Output; D003999:Dichloroacetic Acid / Q000494:pharmacology; D004285:Dogs; D004731:Endotoxins; D004789:Enzyme Activation; D004926:Escherichia coli; D005260:Female; D006614:Hindlimb / Q000098:blood supply; D007082:Ileum / Q000098:blood supply / Q000378:metabolism; D007773:Lactates / Q000097:blood*; D008297:Male; D010100:Oxygen / Q000097:blood*; D010101:Oxygen Consumption; D011768:Pyruvate Dehydrogenase Complex / Q000378:metabolism; D012039:Regional Blood Flow; D012772:Shock, Septic / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D014655:Vascular Resistance
chemical_list: D004731:Endotoxins; D007773:Lactates; D011768:Pyruvate Dehydrogenase Complex; D003999:Dichloroacetic Acid; D010100:Oxygen