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
Most Viewed Current Articles
15 Aug 2023 : Review article 7,203
Free-Circulating Nucleic Acids as Biomarkers in Patients After Solid Organ TransplantationDOI :10.12659/AOT.939750
Ann Transplant 2023; 28:e939750
03 Jan 2023 : Original article 7,086
Impact of Autologous Stem Cell Transplantation on Primary Central Nervous System Lymphoma in First-Line and...DOI :10.12659/AOT.938467
Ann Transplant 2023; 28:e938467
16 May 2023 : Original article 6,914
Breaking Antimicrobial Resistance: High-Dose Amoxicillin with Clavulanic Acid for Urinary Tract Infections ...DOI :10.12659/AOT.939258
Ann Transplant 2023; 28:e939258
28 May 2024 : Original article 6,394
Effect of Dexmedetomidine Combined with Remifentanil on Emergence Agitation During Awakening from Sevoflura...DOI :10.12659/AOT.943281
Ann Transplant 2024; 29:e943281