Ketamine suppresses tumor necrosis factor-alpha activity and mortality in carrageenan-sensitized endotoxin shock model.
We have reported that an intravenous anesthetic, ketamine, has a potent suppressive effect on lipopolysaccharide (LPS)-induced TNF-alpha production in vitro [Takenaka et al., Anesthesiology 80:402-408, 1994]. The purpose of the present study was to investigate the overall effects of ketamine on hemodynamics, serum TNF-alpha level, arterial blood gases (ABGs), blood glucose level, liver function, and lethality in carrageenan (CAR)-sensitized endotoxemic models. All animals were pretreated intraperitoneally with CAR (150 mg/kg) 16 hr before LPS stimulation. The control rats were injected LPS with 0.5 mg/kg intravenously (i.v.). The ketamine-treated rats were injected with 100 mg/kg of ketamine intramuscularly 30 min before LPS (0.5 mg/kg) i.v. injection, followed by an i.v. infusion at 0, 5, or 10 mg/kg/hr. Serum TNF-alpha, ABGs, blood glucose, and hematological studies were determined at 0, 2, and 6 hr after the LPS challenge. Serum hepatocellular enzyme levels were measured at 6 hr after the injection. In CAR-sensitized rats, serum TNF-alpha activity remarkably increased in accordance with the mild decrease of mean arterial pressure (MAP) at 2 hr after LPS stimulation. In addition, severe metabolic acidosis, hypoglycemia as well as severe hepatic injury were induced at 6 hr after the LPS challenge. By contrast, ketamine treatment significantly attenuated the decrease in MAP and LPS-induced TNF-alpha activity. Ketamine also significantly improved arterial oxygen tension (PaO2), metabolic acidosis and hypoglycemia, and attenuated endotoxin-induced hepatic injury in a dose-dependent fashion. In addition, ketamine treatment significantly improved LPS-induced lethality in CAR-sensitized mice.(ABSTRACT TRUNCATED AT 250 WORDS)
Koga
K
K
Department of Anesthesiology, School of Medicine, University of Occupational and Environmental Health, Japan.
Ogata
M
M
Takenaka
I
I
Matsumoto
T
T
Shigematsu
A
A
D000138:Acidosis / Q000209:etiology / Q000517:prevention & control; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D001794:Blood Pressure; D002245:Carbon Dioxide / Q000097:blood; D002351:Carrageenan / Q000494:pharmacology*; D004731:Endotoxins / Q000008:administration & dosage; D006863:Hydrogen-Ion Concentration; D007003:Hypoglycemia / Q000209:etiology / Q000517:prevention & control; D007649:Ketamine / Q000494:pharmacology* / Q000627:therapeutic use; D007700:Kinetics; D008099:Liver / Q000503:physiopathology; D008107:Liver Diseases / Q000209:etiology / Q000517:prevention & control; D008297:Male; D010100:Oxygen / Q000097:blood; D051381:Rats; D017208:Rats, Wistar; D012772:Shock, Septic / Q000150:complications / Q000401:mortality* / Q000503:physiopathology; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism*
D001786:Blood Glucose; D004731:Endotoxins; D014409:Tumor Necrosis Factor-alpha; D002245:Carbon Dioxide; D007649:Ketamine; D002351:Carrageenan; D010100:Oxygen