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Olprinone attenuates excessive shear stress through up-regulation of endothelial nitric oxide synthase in a rat excessive hepatectomy model.
MedLine Citation:
PMID:  21254346     Owner:  NLM     Status:  In-Data-Review    
Abstract/OtherAbstract:
After extended hepatectomy, excessive shear stress in the remnant liver causes postoperative liver failure. Olprinone (OLP), a selective phosphodiesterase inhibitor, has been reported to improve microcirculation and attenuate inflammation. The aim of this study was to investigate the effects of OLP on shear stress in rats with an excessive hepatectomy (EHx) model. In this study, EHx comprised 90% hepatectomy with ligation of the left and right Glisson's sheaths in Lewis rats. OLP or saline was intraperitoneally administered with an osmotic pump 48 hours before EHx. To evaluate the shear stress, we measured the portal vein (PV) pressure. We also assessed sinusoidal endothelial cell injury by immunohistochemistry and electron microscopy. Furthermore, we assessed apoptosis in the liver with the terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick-end labeling method. Treatment with OLP up-regulated hepatic endothelial nitric oxide synthase (eNOS) expression. The increase in the PV pressure due to Glisson's sheath ligation was attenuated in OLP-treated rats during a 30-minute period after ligation. Treatment with OLP preserved sinusoidal endothelial cells and reduced apoptosis in the remnant liver. The probability of survival in the OLP-treated rats was significantly better than that in the controls (33.3% versus 13.3%). Furthermore, the postoperative eNOS activity in the OLP-treated rats was higher than that in the controls. The administration of Nω-nitro-l-arginine methyl ester to OLP-treated rats eliminated the effects of OLP on PV pressure and survival after EHx. Therefore, we concluded that OLP attenuates excessive shear stress through the up-regulation of eNOS and improves the survival rate after EHx. Liver Transpl 17:60-69, 2011. © 2011 AASLD.
Authors:
Kenya Yamanaka; Etsuro Hatano; Masato Narita; Koji Kitamura; Atsuko Yanagida; Hiroyuki Asechi; Hiromitsu Nagata; Kojiro Taura; Takashi Nitta; Shinji Uemoto
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Liver transplantation : official publication of the American Association for the Study of Liver Diseases and the International Liver Transplantation Society     Volume:  17     ISSN:  1527-6473     ISO Abbreviation:  Liver Transpl.     Publication Date:  2011 Jan 
Date Detail:
Created Date:  2011-01-21     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  100909185     Medline TA:  Liver Transpl     Country:  United States    
Other Details:
Languages:  eng     Pagination:  60-9     Citation Subset:  IM    
Copyright Information:
Copyright © 2011 American Association for the Study of Liver Diseases.
Affiliation:
Department of Surgery, Graduate School of Medicine, Kyoto University, Kyoto, Japan.
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