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14 April 2014 : Original article  

Hydroxyectoine ameliorates preservation injury in deceased after cardiac death donors in experimental liver grafts

Pramod Kadaba SrinivasanABCDEF, Ngwi FetBCDE, Christian BleilevensBCD, Mamdouh AfifyCDE, Benedict DoorschodtDEF, Shintaro YagiACD, Gerhild van Echten-DeckertDEF, René Hany TolbaABCDEF

DOI: 10.12659/AOT.889958

Ann Transplant 2014; 19:165-173

Abstract

BACKGROUND: Due to the drastic shortage of organ donors, clinicians are increasingly considering the use of deceased after cardiac death donors (DCD). Compatible solutes like Ectoine and Hydroxyectoine are produced by extremophilic bacteria as a cell protectant to survive in harsh environments. We hypothesized that the addition of Hydroxyectoine to Histidine-Tryptophan-Ketoglutarate solution (HTK) could ameliorate cold ischemic preservation injury of DCD livers.

MATERIAL AND METHODS: Rat livers were harvested from male Wistar rats weighing 250–300 g. Three experimental groups (n=5 per group) were studied: (1) Controls: cold static storage in HTK for 24 h, (2) DCD: 30-min warm ischemia time and 24-h cold static storage in HTK, and (3) DCD+Hydroxyectoine: like DCD, but with 24-h cold static storage in HTK+Hydroxyectoine. Viability of the livers was assessed after 24 h of preservation by isolated perfusion for 45 min with oxygenated Krebs-Henseleit buffer solution.

RESULTS: (mean ±SEM, Control vs. DCD vs. DCD+Hydroxyectoine) Parenchymal enzyme release was significantly lower in DCD+Hydroxyectoine compared to DCD (AST: 9±0.54; 56.8±2.05; 32.2±7.25 U/L, ALT: 9.5±0.5; 37.75±9.6; 17.5±4.17 U/L). Bile production at the end of 45 min reperfusion was significantly higher in DCD+Hydroxyectoine (5.16±1.32; 1.36±0.34; 10.75±2.24 µL/g liver weight/45 min). Malondialdehyde values were significantly lower in DCD+Hydroxyectoine (0.8±0.09, 1.14±0.18, 0.77±0.08 nmol/mL). Intercellular adhesion molecule-1 showed significantly lower values in DCD+Hydroxyectoine (219.07±51.79, 431.9±35.70, 205.2±37.71 pg/mL) and the portal venous pressure at 45 min was lower compared to DCD (20.41±0.12, 27.47±0.45, 22.08±0.78 mmHg).

CONCLUSIONS: Our data provide evidence for the beneficial role of Hydroxyectoine-modified HTK solution for the preservation of DCD livers compared to HTK.

Keywords: , cold ischemia, Organ Preservation, Ischemia-Reperfusion Injury, HTK, Hydroxyectoine

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