Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia

• Published in: Journal of anesthesia Vol. 19; no. 4; pp. 295 - 301
• Main Authors: Kuniyoshi, Tamotsu, Kakihana, Yasuyuki, Isowaki, Sumikazu, Nagata, Etsuro, Tobo, Kazumi, Kaminosono, Tatsuya, Hashiguchi, Tetsuaki, Tahara, Masamichi, Kawamae, Hirokazu, Okayama, Naoko, Kanmura, Yuichi
• Format: Journal Article
• Language: English
• Published: Japan Springer 07.11.2005
• Subjects: Animals; Care and treatment; Disease Models, Animal; Dosage and administration; Electron Transport Complex IV - metabolism; Endotoxemia - drug therapy; Endotoxemia - etiology; Endotoxemia - metabolism; Endotoxins; Hemoglobins - metabolism; Imidazoles - administration & dosage; Imidazoles - pharmacology; Lactic Acid - blood; Liver Circulation - drug effects; Liver failure; Male; Mitochondria, Liver - drug effects; Mitochondria, Liver - metabolism; Oxygen Consumption; Phosphodiesterase Inhibitors - administration & dosage; Phosphodiesterase Inhibitors - pharmacology; Phosphodiesterases; Pyridones - administration & dosage; Pyridones - pharmacology; Splanchnic Circulation - drug effects; Swine; Japan
• ISSN: 0913-8668; 1438-8359
• DOI: 10.1007/s00540-005-0340-2

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. 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. 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). 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.