Effects of olprinone on hepatosplanchnic circulation and mitochondrial oxidation in a porcine model of endotoxemia |
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Authors: | Tamotsu Kuniyoshi Yasuyuki Kakihana Sumikazu Isowaki Etsuro Nagata Kazumi Tobo Tatsuya Kaminosono Tetsuaki Hashiguchi Masamichi Tahara Hirokazu Kawamae Naoko Okayama Yuichi Kanmura |
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Institution: | (1) Department of Anesthesiology and Critical Care Medicine, Kagoshima University School of Medicine, 8-35-1 Sakuragaoka, Kagoshima 890-8520, Japan;(2) Division of Intensive Care Medicine, Kagoshima University Hospital, Kagoshima, Japan |
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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 VO2H 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. |
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Keywords: | Olprinone Endotoxemia Hepatic blood flow Hepatic oxygen delivery Cytochrome aa3 |
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