The effect of etomidate pretreatment on cerebral high energy metabolites, lactate, and glucose during severe hypoxia in the rat.
Etomidate was compared with thiopental with respect to preventing loss of brain high energy metabolites and accumulation of lactate during 20 min of hypoxemia (Pa2 of 16-19 mmHg) in rats with unilateral carotid artery ligation. Male Sprague-Dawley rats, anesthetized with halothane and nitrous oxide (N2O) in oxygen were randomly assigned to one of six groups. A normoxic control group which received 70% N2O in oxygen, a hypoxia group received no iv drug treatment (hypoxia-N2O), and four iv drug treatment groups (N2O was replaced by 70% nitrogen at the start of drug administration). The iv drug groups were treated as follows: hypoxia-etomidate low dose (1 mg.kg-1 iv followed by an infusion at 0.35 mg.kg-1.min-1); hypoxia-etomidate high dose (1 mg.kg-1 then 1.3 mg.kg-1.min-1); hypoxia-thiopental low dose (15 mg.kg-1, then 1.5 mg.kg-1.min-1); and hypoxia-thiopental high dose (15 mg.kg-1, then 5 mg.kg-1.min-1). After hypoxia or a corresponding period in the normoxic group, the brains were frozen in situ for later biochemical analysis. Blood was obtained prior to and at the end of hypoxia and analyzed for glucose. Brain metabolite concentrations on the side ipsilateral to the ligated carotid artery in the normoxia-N2O group were adenosine triphosphate (ATP), 2.76 +/- 0.1, phosphocreatione (PCr) 3.88 +/- 0.12, lactate 2.34 +/- 0.16, and glucose 3.56 +/- 0.28 (mumole.g-1 wet weight, mean +/- SE). There was no significant decrease in ATP in any of the hypoxia groups. PCr decreased by 45% (compared to normoxia-N2O) in the hypoxia-N2O group.(ABSTRACT TRUNCATED AT 250 WORDS)
Smith
D S
DS
Department of Anesthesiology, Hahnemann University, Philadelphia, Pennsylvania 19102.
Keykhah
M M
MM
O'Neill
J J
JJ
Harp
J R
JR
D000818:Animals; D001921:Brain / Q000187:drug effects* / Q000378:metabolism; D001923:Brain Chemistry / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005045:Etomidate / Q000008:administration & dosage / Q000494:pharmacology*; D005947:Glucose / Q000378:metabolism*; D006221:Halothane; D000860:Hypoxia / Q000378:metabolism*; D007773:Lactates / Q000378:metabolism*; D019344:Lactic Acid; D008297:Male; D009609:Nitrous Oxide; D011897:Random Allocation; D051381:Rats; D011919:Rats, Inbred Strains; D013874:Thiopental / Q000008:administration & dosage / Q000494:pharmacology
D007773:Lactates; D019344:Lactic Acid; D005947:Glucose; D013874:Thiopental; D009609:Nitrous Oxide; D006221:Halothane; D005045:Etomidate