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Evaluation of a Modified HTK Solution Containing the New Iron Chelator LK 614 in an Isolated Rat Liver Perfusion Model
Authors:Shengli Wu  Jeremias Wohlschlaeger  Herbert de Groot  Ursula Rauen
Affiliation:1. Institut für Physiologische Chemie, Universit?tsklinikum, Hufelandstr. 55, D-45122, Essen, Germany;2. Institut für Pathologie und Neuropathologie, Universit?tsklinikum, Hufelandstr. 55, D-45122, Essen, Germany
Abstract:
Background: Cold storage-induced injury to donor organs remains a persistent problem in transplantation medicine. We here evaluated a modified HTK solution including, among others, a new, membrane-permeable iron chelator, LK 614, in the isolated perfused rat liver model. Methods: Rat livers were stored at 4°C for 24 hr in modified HTK solution, in modified HTK solution with LK 614 or in traditional HTK solution, and reperfused for 60 min at 37°C with Krebs-Henseleit buffer (KH buffer). Bile secretion and lactate dehydrogenase (LDH) release into the perfusate were measured, and hepatic microcirculation evaluated optically after the addition of trypan blue to the perfusate. Biopsies were evaluated by a pathologist blinded to the experimental conditions. Results: Compared with HTK-preserved livers, LDH leakage was significantly lower and bile secretion significantly higher in the modified HTK solution with the iron chelator (both p <. 05), while values for the modified solution without the iron chelator were in between (no significant difference to either of the two other solutions). The hepatic microcirculation was also preserved best in livers stored in the modified HTK solution with LK 614. Histomorphological investigation confirmed the improved preservation in the modified HTK solution with LK 614. Conclusions: These results suggest that livers might be better preserved in modified HTK solution containing the iron chelator LK 614 (and also, but less so, in the modified solution without the iron chelator) than in the original HTK solution, and such a modified solution should now be evaluated in an animal model of liver transplantation.
Keywords:liver preservation  HTK solution  preservation solution  iron chelator  hydroxamic acid  deferoxamine  glycine  alanine  arginine  N-acetylhistidine
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