title: Cilostazol improves hepatic blood perfusion, microcirculation, and liver regeneration after major hepatectomy in rats.
abstract: 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.
authors.affiliation: Department of General, Visceral, Vascular, and Paediatric Surgery.
authors.forename: Maximilian
authors.initials: M
authors.lastname: von Heesen
authors.affiliation: Department of General, Visceral, Vascular, and Paediatric Surgery.
authors.forename: Stefan
authors.initials: S
authors.lastname: Dold
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Simon
authors.initials: S
authors.lastname: Müller
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Claudia
authors.initials: C
authors.lastname: Scheuer
authors.affiliation: Department of General, Visceral, Vascular, and Paediatric Surgery.
authors.forename: Otto
authors.initials: O
authors.lastname: Kollmar
authors.affiliation: Department of General, Visceral, Vascular, and Paediatric Surgery.
authors.forename: Martin K
authors.initials: MK
authors.lastname: Schilling
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Michael D
authors.initials: MD
authors.lastname: Menger
authors.affiliation: Institute for Clinical and Experimental Surgery, University of Saarland, Homburg/Saar, Germany.
authors.forename: Mohammed R
authors.initials: MR
authors.lastname: Moussavian
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001646:Bile / Q000378:metabolism; D000077407:Cilostazol; D004353:Drug Evaluation, Preclinical; D005260:Female; D008099:Liver / Q000187:drug effects / Q000378:metabolism; D008102:Liver Circulation / Q000187:drug effects*; D017093:Liver Failure / Q000517:prevention & control*; D008115:Liver Regeneration / Q000187:drug effects*; D023421:Models, Animal; D058987:Phosphodiesterase 3 Inhibitors / Q000494:pharmacology / Q000627:therapeutic use*; D017207:Rats, Sprague-Dawley; D013777:Tetrazoles / Q000494:pharmacology / Q000627:therapeutic use*; D016212:Transforming Growth Factor beta / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D058987:Phosphodiesterase 3 Inhibitors; D013777:Tetrazoles; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; C467498:vascular endothelial growth factor A, rat; D000077407:Cilostazol