title: Systematic evaluation of nitric oxide, tetrahydrobiopterin, and anandamide levels in a porcine model of endotoxemia.
abstract: OBJECTIVE
  Using a lipopolysaccharide (LPS)-treated porcine model, we examined: (1) whether nitric oxide (NO), anandamide, and tetrahydrobiopterin (BH4) increased or not in early endotoxic shock; and (2) the location of the major site of production of these molecules, by comparing their concentrations in arteries and the portal and hepatic veins.
  
  
  METHODS
  Ten pigs received an infusion of LPS at 1.7 microg x kg(-1)x h(-1) via the portal vein for 240 min. Consecutive changes in systemic hemodynamics, hepatosplanchnic circulation, and oxygen delivery were measured. Furthermore, the variable changes in the concentrations of nitrite and nitrate (NOx), anandamide, and BH4 were measured. To access the effects of surgery, anesthesia, and fluid management on BH4, an experiment without LPS infusion was performed in two other animals.
  
  
  RESULTS
  Mean arterial pressure and cardiac index started to decrease at 60 min after LPS infusion. However, systemic vascular resistance remained unchanged. Total hepatic blood flow and hepatic oxygen delivery also decreased significantly. NOx and anandamide did not change during LPS infusion. BH4 values did not change without LPS infusion. However, BH4 values increased significantly in the arterial, portal, and hepatic circulation during LPS infusion, especially in the hepatic vein (from 136.8 +/- 27.5 to 281.3 +/- 123.2 mol/ml; P < 0.01).
  
  
  CONCLUSIONS
  Our data suggest that the BH4 values were significantly increased in several organs, especially in the liver during endotoxic shock. Impaired cardiac output and decreased blood pressure appeared in the early phase of porcine endotoxemia. Longer-term observation of these parameters after LPS treatment should be performed as the next step in future studies.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kakihana
authors.forename: Sumikazu
authors.initials: S
authors.lastname: Isowaki
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kuniyoshi
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kaminosono
authors.forename: Etsuro
authors.initials: E
authors.lastname: Nagata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tobo
authors.forename: Masamichi
authors.initials: M
authors.lastname: Tahara
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Yuki
authors.initials: Y
authors.lastname: Arakawa
authors.forename: Yoshie
authors.initials: Y
authors.lastname: Kakihara
authors.forename: Tsuyoshi
authors.initials: T
authors.lastname: Goromaru
authors.forename: Nobuo
authors.initials: N
authors.lastname: Nakanishi
authors.forename: Hiroe
authors.initials: H
authors.lastname: Nakazawa
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanmura
mesh_terms: D000818:Animals; D001095:Arachidonic Acids / Q000097:blood*; D001708:Biopterins / Q000031:analogs & derivatives* / Q000097:blood; D004195:Disease Models, Animal; D063388:Endocannabinoids; D019446:Endotoxemia / Q000097:blood* / Q000503:physiopathology; D006439:Hemodynamics / Q000502:physiology; D019344:Lactic Acid / Q000097:blood; D008102:Liver Circulation; D008297:Male; D009569:Nitric Oxide / Q000097:blood*; D053284:Polyunsaturated Alkamides / Q000097:blood*; D011168:Portal System / Q000503:physiopathology; D013552:Swine
chemical_list: D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D001708:Biopterins; D009569:Nitric Oxide; D019344:Lactic Acid; C003402:sapropterin; C078814:anandamide