Naloxone therapy in awake endotoxemic Yucatan minipigs.
Twelve Yucatan miniature pigs were fitted with jugular, portal, hepatic vein, and carotid artery catheters, and hepatic artery and portal vein flow cuffs to quantitate portosystemic and transhepatic kinetics. Seventy-two hours later they were placed in slings, and following a 3-hr control period were infused with Escherichia coli endotoxin at 15 micrograms/kg/hr for 6 hr. Eight were controls and 4 received a primed (2 mg/kg) continuous infusion (2 mg/kg/hr) of naloxone 1 hr after initiation of endotoxin. In the naloxone group, arterial hypotension developed by 60 min. Arterial pressure increased to 125 mm Hg by 80 min (20 min post naloxone) and maintained this level for 3 hr. [6-3H]Glucose-derived rate of disappearance (Rd) values were increased above their own control period at 60 and 80 min, but were approximately 55% lower than untreated controls. Rate of appearance (Ra) values remained unchanged in the naloxone group resulting in a net glucose deficit. After 1 hr of endotoxin, blood pyruvate increased from 1.0 to 1.8 mg%, reached 3.3 mg% at 80 min, and remained elevated. Blood lactate similarly increased from 11 to 35 mg% by 60 min, increasing further to 82 mg% 20 min after naloxone infusion, in concert with signs of severe distress. Portal and hepatic total O2 decreased by 60 min and 100 min, respectively, reflecting depressed hepatic O2, input. Lethality was 75% in naloxone-treated pigs by the end of the experiment, vs 0% in untreated animals. Naloxone improves some hemodynamic parameters. However, in these conscious postsurgical patients, naloxone blocked some beneficial effects of endogenous opiates resulting in severe metabolic derangements and increased mortality.
D000818:Animals; D001786:Blood Glucose / Q000032:analysis; D004731:Endotoxins / Q000097:blood*; D004926:Escherichia coli; D005260:Female; D006439:Hemodynamics / Q000187:drug effects; D007328:Insulin / Q000097:blood; D007700:Kinetics; D007773:Lactates / Q000097:blood; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects; D009270:Naloxone / Q000494:pharmacology / Q000627:therapeutic use*; D010100:Oxygen / Q000097:blood; D010101:Oxygen Consumption; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine; D013556:Swine, Miniature
D001786:Blood Glucose; D004731:Endotoxins; D007328:Insulin; D007773:Lactates; D009270:Naloxone; D010100:Oxygen