1. Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia.
- Author
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Kuniyoshi T, Kakihana Y, Isowaki S, Nagata E, Tobo K, Kaminosono T, Hashiguchi T, Tahara M, Kawamae H, Okayama N, and Kanmura Y
- Subjects
- Animals, Disease Models, Animal, Electron Transport Complex IV metabolism, Endotoxemia etiology, Endotoxemia metabolism, Endotoxins, Hemoglobins metabolism, Imidazoles administration & dosage, Lactic Acid blood, Liver Circulation drug effects, Male, Mitochondria, Liver metabolism, Oxygen Consumption, Phosphodiesterase Inhibitors administration & dosage, Pyridones administration & dosage, Splanchnic Circulation drug effects, Swine, Endotoxemia drug therapy, Imidazoles pharmacology, Mitochondria, Liver drug effects, Phosphodiesterase Inhibitors pharmacology, Pyridones pharmacology
- Abstract
Purpose: 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)., Conclusion: 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.
- Published
- 2005
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