Evaluation of a modified HTK solution containing the new iron chelator LK 614 in an isolated rat liver perfusion model.
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 degrees 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 degrees 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.
Wu
Shengli
S
Institut für Physiologische Chemie, Universitätsklinikum, Essen, Germany.
Wohlschlaeger
Jeremias
J
de Groot
Herbert
H
Rauen
Ursula
U
D000818:Animals; D005947:Glucose / Q000494:pharmacology; D066298:In Vitro Techniques; D007502:Iron Chelating Agents / Q000494:pharmacology*; D008099:Liver / Q000187:drug effects* / Q000473:pathology; D008102:Liver Circulation / Q000187:drug effects; D008297:Male; D008353:Mannitol / Q000494:pharmacology; D008833:Microcirculation / Q000187:drug effects; D009926:Organ Preservation / Q000379:methods; D019188:Organ Preservation Solutions / Q000494:pharmacology*; D010477:Perfusion / Q000379:methods; D011189:Potassium Chloride / Q000494:pharmacology; D011343:Procaine / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D014325:Tromethamine
C039984:Bretschneider cardioplegic solution; D007502:Iron Chelating Agents; C074097:Krebs-Henseleit solution; D019188:Organ Preservation Solutions; D014325:Tromethamine; D008353:Mannitol; D011343:Procaine; D011189:Potassium Chloride; D005947:Glucose