title: Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia.
abstract: 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.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan.
authors.forename: Tamotsu
authors.initials: T
authors.lastname: Kuniyoshi
authors.forename: Yasuyuki
authors.initials: Y
authors.lastname: Kakihana
authors.forename: Sumikazu
authors.initials: S
authors.lastname: Isowaki
authors.forename: Etsuro
authors.initials: E
authors.lastname: Nagata
authors.forename: Kazumi
authors.initials: K
authors.lastname: Tobo
authors.forename: Tatsuya
authors.initials: T
authors.lastname: Kaminosono
authors.forename: Tetsuaki
authors.initials: T
authors.lastname: Hashiguchi
authors.forename: Masamichi
authors.initials: M
authors.lastname: Tahara
authors.forename: Hirokazu
authors.initials: H
authors.lastname: Kawamae
authors.forename: Naoko
authors.initials: N
authors.lastname: Okayama
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Kanmura
mesh_terms: 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
chemical_list: 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