Logo Annals of Transplantation Logo Annals of Transplantation Logo Annals of Transplantation

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. MoussavianACDG

DOI: 10.12659/AOT.893031

Ann Transplant 2015; 20:160-168


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

Add Comment 0 Comments

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 Recipients

Ann Transplant In Press; DOI:  

Most Viewed Current Articles

24 Aug 2021 : Review article  

Normothermic Machine Perfusion (NMP) of the Liver – Current Status and Future Perspectives

DOI :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 Models

DOI :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

Your Privacy

We use cookies to ensure the functionality of our website, to personalize content and advertising, to provide social media features, and to analyze our traffic. If you allow us to do so, we also inform our social media, advertising and analysis partners about your use of our website, You can decise for yourself which categories you you want to deny or allow. Please note that based on your settings not all functionalities of the site are available. View our privacy policy.

Annals of Transplantation eISSN: 2329-0358
Annals of Transplantation eISSN: 2329-0358