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Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats
Author(s) -
von Heesen Maximilian,
Dold Stefan,
Müller Simon,
Scheuer Claudia,
Kollmar Otto,
Schilling Martin K.,
Menger Michael D.,
Moussavian Mohammed R.
Publication year - 2015
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.24114
Subject(s) - medicine , liver regeneration , hepatectomy , cilostazol , liver transplantation , microcirculation , liver function , perfusion , blood flow , transplantation , regeneration (biology) , urology , surgery , biology , aspirin , resection , microbiology and biotechnology
Major hepatectomy or small‐for‐size liver transplantation may result in postoperative liver failure. So far, no treatment is available to improve liver regeneration. Herein, we studied whether cilostazol, a selective phosphodiesterase III inhibitor, is capable of improving liver regeneration after major hepatectomy. Sprague‐Dawley rats (n = 74) were treated with cilostazol (5 mg/kg daily) or a glucose solution and underwent either 70% liver resection or a sham operation. Before and after surgery, hepatic arterial and portal venous blood flow and hepatic microvascular perfusion were analyzed. Liver morphology, function, and regeneration were studied with histology, immunohistochemistry, western blotting, and bile excretion analysis. Cilostazol significantly increased hepatic blood flow and microcirculation before and after hepatectomy in comparison with sham‐operated controls. This was associated with an elevation of hepatic vascular endothelial growth factor expression, an increase of hepatocellular proliferation, and an acceleration of liver regeneration. Furthermore, cilostazol protected the tissue of the remnant liver as indicated by an attenuation of hepatocellular disintegration. In conclusion, cilostazol increases hepatic blood perfusion, microcirculation, and liver regeneration after a major hepatectomy. Thus, cilostazol may represent a novel strategy to reduce the rate of liver failure after both extended hepatectomy and small‐for‐size liver transplantation. Liver Transpl 21:792–800, 2015 . © 2015 AASLD.