title: Sublethal endotoxin administration evokes super-resistance to systemic hypoxia in rats.
abstract: BACKGROUND
  Systemic hypoxia following surgical injury modulates cytokine and catecholamine responses. Endotoxin tolerance develops after pretreatment of animals with sublethal endotoxin doses and is characterized by a reduced inflammatory cytokine response to subsequent endotoxin challenges. The administration of endotoxin also attenuates ischemic injury of rat myocardial tissue following hypoxia, a phenomenon described as cross-tolerance. The objectives of this study were: 1) to determine whether endotoxin evokes a cross-tolerance to systemic hypoxia in rats; and 2) to estimate circulatory and pulmonary performance in rats with systemic hypoxia after endotoxin pretreatment.
  
  
  METHODS
  Seventy-two hours before the experiment, Wistar rats were given an intraperitoneal injection of endotoxin at a dose of 10 microg/kg. Polyethylene catheters were inserted into the femoral vein for infusion, and into the femoral artery for blood sampling and blood pressure monitoring. Systemic hypoxia was achieved by continuous inhalation of a modified gas mixture (9% oxygen+ 91% N2) for 4 hours. Plasma TNF-alpha and IL-6 were measured by ELISA, and norepinephrine (NE) by HPLC.
  
  
  RESULTS
  The hypoxic rats that were pretreated with saline showed a significant decrease in mean arterial blood and base excess, as compared with the normoxic rats. Endotoxin pretreatment prevented the drop in mean arterial pressure during hypoxia and reduced the decrease in base excess. Hypoxic conditions markedly stimulated TNF-alpha and IL-6 release and increased NE levels, compared to the normoxic rats. Pretreatment with endotoxin suppressed the hypoxia-induced cytokine production as well as attenuating the increase in NE levels
  
  
  CONCLUSIONS
  In this rat hypoxia model, endotoxin pretreatment ameliorated the hypoxia-induced inflammatory response as well as suppressing the effects on arterial oxygenation, anaerobic metabolism and NE stimulation.
authors.affiliation: Department of Gastrointestinal Surgery, University of Tokyo, Japan. naki@bd.mbn.or.jp
authors.forename: Naoki
authors.initials: N
authors.lastname: Hiki
authors.forename: Yoshikazu
authors.initials: Y
authors.lastname: Mimura
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hatao
authors.forename: Junichi
authors.initials: J
authors.lastname: Kojima
authors.forename: Toshihisa
authors.initials: T
authors.lastname: Ogawa
authors.forename: Eiichi
authors.initials: E
authors.lastname: Tsuji
authors.forename: Michio
authors.initials: M
authors.lastname: Kaminishi
mesh_terms: D000222:Adaptation, Physiological / Q000187:drug effects*; D000818:Animals; D001794:Blood Pressure; D004305:Dose-Response Relationship, Drug; D004731:Endotoxins / Q000008:administration & dosage / Q000627:therapeutic use*; D004797:Enzyme-Linked Immunosorbent Assay; D004837:Epinephrine / Q000097:blood; D000860:Hypoxia / Q000378:metabolism / Q000517:prevention & control*; D007249:Inflammation / Q000517:prevention & control*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D017202:Myocardial Ischemia / Q000517:prevention & control; D051381:Rats; D017208:Rats, Wistar; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: D004731:Endotoxins; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D004837:Epinephrine