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Hepatoprotective effect by pretreatment with olprinone in a swine partial hepatectomy model
Author(s) -
Iguchi Kohta,
Hatano Etsuro,
Yamanaka Kenya,
Sato Motohiko,
Yamamoto Gen,
Kasai Yosuke,
Okamoto Tatsuya,
Okuno Masayuki,
Taura Kojiro,
Fukumoto Kyoko,
Ueno Kazuyuki,
Uemoto Shinji
Publication year - 2014
Publication title -
liver transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.814
H-Index - 150
eISSN - 1527-6473
pISSN - 1527-6465
DOI - 10.1002/lt.23884
Subject(s) - medicine , hepatectomy , liver transplantation , saline , prothrombin time , indocyanine green , ligation , transplantation , gastroenterology , anesthesia , surgery , resection
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. Liver Transpl 20:838–849, 2014 . © 2014 AASLD.