26 March 2015 : Original article
Preconditioning by Cilostazol Protects against Cold Hepatic Ischemia-Reperfusion Injury
Maximilian von HeesenABCDEF, Simon MüllerBC, Ulrich KepplerBE, Moritz J. StrowitzkiBE, Claudia ScheuerC, Martin K. SchillingADG, Michael D. MengerADEF, Mohammed R. MoussavianACDGDOI: 10.12659/AOT.893031
Ann Transplant 2015; 20:160-168
Abstract
BACKGROUND: In liver transplantation, prolonged cold storage and post-transplant reperfusion are associated with endothelial inflammation, organ dysfunction, and graft failure. We herein studied whether cilostazol, a phosphodiesterase-3-inhibitor, attenuates post-ischemic liver injury after prolonged cold storage.
MATERIAL AND METHODS: Sprague-Dawley rats were assigned to 5 groups (n=6 each): sham animals (cold storage time (CST): 1 h), vehicle-treated (NaCl 0.9%) controls (CST: 24 h), and animals receiving 0.1, 1.0, or 10.0 mg/kg body weight (BW) cilostazol pre-treatment (CST: 24 h). After organ explantation, all livers were stored at 4°C in HTK solution, followed by 60 min of reperfusion with 37°C Krebs Henseleit buffer in a non-recirculating ex situ system. Bile flow was measured to evaluate liver function. To analyze inflammation and morphology, liver tissue samples were taken and histology, immunohistochemistry, and Western blotting were conducted.
RESULTS: In vehicle-treated controls, prolonged cold storage and warm reperfusion induced inflammation, organ dysfunction, and cell death. This was indicated by an increase of hepatocellular vacuolization, endothelial ICAM-1 expression, and apoptotic cell death compared to sham animals. Cilostazol pre-treatment protected against cold hepatic ischemia-reperfusion injury by preventing hepatocellular disintegration, ICAM-1-associated endothelial inflammation, and apoptotic death.
CONCLUSIONS: Inhibition of PDE3 reduces endothelial cell activation and hepatocellular injury in cold ischemia/reperfusion of the liver.
Keywords: Cyclic AMP, Microcirculation, Organ Preservation, Reperfusion Injury
1003 14
In Press
10 Nov 2023 : Original article
Effects of Preservation of Donor Liver Gastroduodenal Artery on Post-Transplant Biliary Complications in 18...Ann Transplant In Press; DOI:
07 Nov 2023 : Original article
Allogeneic Hematopoietic Stem Cell Transplantation Can Improve Prognosis of Extramedullary Infiltration Pos...Ann Transplant In Press; DOI:
06 Nov 2023 : Original article
Clinical Outcomes of Administration of Rituximab for Desensitization in Liver Transplant Patients with Pref...Ann Transplant In Press; DOI:
06 Nov 2023 : Original article
Short-Term Monitoring of Graft Regeneration in Partial Liver Transplantation RecipientsAnn Transplant In Press; DOI:
Most Viewed Current Articles
24 Aug 2021 : Review article
Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future PerspectivesDOI :10.12659/AOT.931664
Ann Transplant 2021; 26:e931664
26 Jan 2022 : Review article
Recurrence of Hepatocellular Carcinoma After Liver Transplantation: Risk Factors and Predictive ModelsDOI :10.12659/AOT.934924
Ann Transplant 2022; 27:e934924
29 Dec 2021 : Original article
Efficacy and Safety of Tacrolimus-Based Maintenance Regimens in De Novo Kidney Transplant Recipients: A Sys...DOI :10.12659/AOT.933588
Ann Transplant 2021; 26:e933588
15 Mar 2022 : Case report
Combined Liver, Pancreas-Duodenum, and Kidney Transplantation for Patients with Hepatitis B Cirrhosis, Urem...DOI :10.12659/AOT.935860
Ann Transplant 2022; 27:e935860