Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia.
OBJECTIVE
This study was performed in order to assess the effects of olprinone, a phosphodiesterase III inhibitor, on hepatic oxygen delivery (DO2H), oxygen consumption (VO2H), and mitochondrial oxidation in the liver of a porcine endotoxemia model.


METHODS
Fourteen pigs received continuous infusion of endotoxin via the portal vein for 240 min. From t = 150 to t = 240 min, animals were randomly divided into two groups to receive saline (control [CONT]; n = 7), or olprinone (OLP; n = 7) via the central vein.


RESULTS
In the OLP group, prior to olprinone treatment at 150 min, endotoxin induced significant decreases in the cardiac index (CI; from 120 +/- 31 to 65 +/- 13 ml.kg(-1).min(-1); P < 0.01) and DO2H (from 3.58 +/- 0.81 to 1.55 +/- 0.49 ml.kg(-1).min(-1); P < 0.01), while VO2H was maintained. After administration of olprinone (from t = 150 to t = 240 min), CI was unchanged, while DO2H increased from 1.55 +/- 0.49 to 1.93 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01) and VO(2)H increased from 0.42 +/- 0.28 to 0.69 +/- 0.38 ml.kg(-1).min(-1) (P < 0.01). At t = 240 min, the oxidation level of cytochrome aa3 was significantly higher in the OLP group than in the CONT group (OLP, 66.2 +/- 19.3% vs CONT, 26.4 +/- 17.3%; P < 0.01).


CONCLUSIONS
Our data for this porcine endotoxemia model suggest that olprinone may have beneficial therapeutic effects in restoring not only systemic and hepatic circulation but also mitochondrial oxidation in the liver.
Kuniyoshi
Tamotsu
T
Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
Kakihana
Yasuyuki
Y
Isowaki
Sumikazu
S
Nagata
Etsuro
E
Tobo
Kazumi
K
Kaminosono
Tatsuya
T
Hashiguchi
Tetsuaki
T
Tahara
Masamichi
M
Kawamae
Hirokazu
H
Okayama
Naoko
N
Kanmura
Yuichi
Y
D000818:Animals; D004195:Disease Models, Animal; D003576:Electron Transport Complex IV / Q000378:metabolism; D019446:Endotoxemia / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism; D004731:Endotoxins; D006454:Hemoglobins / Q000378:metabolism; D007093:Imidazoles / Q000008:administration & dosage / Q000494:pharmacology*; D019344:Lactic Acid / Q000097:blood; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008930:Mitochondria, Liver / Q000187:drug effects* / Q000378:metabolism; D010101:Oxygen Consumption; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000494:pharmacology*; D011728:Pyridones / Q000008:administration & dosage / Q000494:pharmacology*; D013152:Splanchnic Circulation / Q000187:drug effects; D013552:Swine
D004731:Endotoxins; D006454:Hemoglobins; D007093:Imidazoles; D010726:Phosphodiesterase Inhibitors; D011728:Pyridones; D019344:Lactic Acid; C059498:olprinone; C044101:endotoxin, Escherichia coli; D003576:Electron Transport Complex IV