Systematic evaluation of nitric oxide, tetrahydrobiopterin, and anandamide levels in a porcine model of endotoxemia.
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.
Hashiguchi
Tetsuaki
T
Department of Anesthesiology and Critical Care Medicine, Kagoshima University Graduate School of Medical and Dental Science, Kagoshima, Japan.
Kakihana
Yasuyuki
Y
Isowaki
Sumikazu
S
Kuniyoshi
Tamotsu
T
Kaminosono
Tatsuya
T
Nagata
Etsuro
E
Tobo
Kazumi
K
Tahara
Masamichi
M
Okayama
Naoko
N
Arakawa
Yuki
Y
Kakihara
Yoshie
Y
Goromaru
Tsuyoshi
T
Nakanishi
Nobuo
N
Nakazawa
Hiroe
H
Kanmura
Yuichi
Y
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
D001095:Arachidonic Acids; D063388:Endocannabinoids; D053284:Polyunsaturated Alkamides; D001708:Biopterins; D009569:Nitric Oxide; D019344:Lactic Acid; C003402:sapropterin; C078814:anandamide