Hepatoprotective effect by pretreatment with olprinone in a swine partial hepatectomy model.
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説明
Excessive portal flow to a small remnant liver or small-for-size graft is a primary factor of small-for-size syndrome. We demonstrated that olprinone (OLP), a phosphodiesterase III inhibitor, had a hepatoprotective effect in a rat extended hepatectomy model and a small-for-size liver transplantation model through a modification of the portal venous pressure (PVP). To identify the appropriate dose and duration of treatment for clinical applications, we conducted experiments with a swine partial hepatectomy model. Twenty microminipigs were divided into 4 groups that received the following treatments: (A) saline (control group), (B) OLP at 0.3 μg/kg/minute (preoperative and postoperative administration), (C) OLP at 0.1 μg/kg/minute (preoperative administration), and (D) OLP at 0.3 μg/kg/minute (preoperative administration). The pigs underwent 70% partial hepatectomy. Hemodynamic changes, including changes in PVP, were examined. Liver biopsy was performed 1 and 3 hours after hepatectomy. Blood samples were collected until postoperative day 7 (POD7). In comparison with group A, PVP elevations, periportal edema, and sinusoidal hemorrhaging were attenuated after left Glisson's ligation in groups C and D. Pretreatment with OLP in groups C and D preserved the microstructure of sinusoids and improved the prothrombin activity 1 and 3 hours after hepatectomy. These animals showed better recovery of the remnant liver volume and the plasma disappearance rate of indocyanine green on POD7. In contrast, group B showed exacerbation of liver damage. Measurements of the serum OLP concentration showed that 10 ng/mL OLP was appropriate for a hepatoprotective effect. In conclusion, pretreatment with OLP shows hepatoprotective effects in a swine partial hepatectomy model. OLP may have the potential to ameliorate patients' outcomes after hepatectomy or liver transplantation.
収録刊行物
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- Liver transplantation
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Liver transplantation 20 (7), 838-849, 2014-07
wiley
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キーワード
- Animals
- Bilirubin/blood
- Biopsy
- Edema
- Endothelial Cells/cytology
- Enzyme Inhibitors/therapeutic use
- Female
- Hemodynamics
- Hepatectomy/adverse effects
- Hepatectomy/methods
- Imidazoles/therapeutic use
- Immunohistochemistry
- Laparotomy
- Liver/pathology
- Liver Transplantation/adverse effects
- Microscopy, Electron
- Nitric Oxide Synthase Type III/metabolism
- Phosphodiesterase 3 Inhibitors/therapeutic use
- Portal Pressure
- Postoperative Period
- Prothrombin/metabolism
- Pyridones/therapeutic use
- Swine
- Swine, Miniature
- Translational Medical Research
- Treatment Outcome
詳細情報 詳細情報について
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- CRID
- 1050845760743772032
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- NII論文ID
- 120005652823
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- ISSN
- 15276473
- 15276465
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- DOI
- 10.1002/lt.23884
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- HANDLE
- 2433/199896
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- PubMed
- 24700629
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- 本文言語コード
- en
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- 資料種別
- journal article
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- データソース種別
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- IRDB
- Crossref
- CiNii Articles
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- OpenAIRE