SAFETY AND FEASIBILITY OF MODIFIED HISTIDINE-TRYPTOPHAN-KETOGLUTARATE SOLUTION FOR LIVER PRESERVATION PRIOR TRANSPLANTATION

Gernot M. Kaiser¹, Matthias Heuer¹, Renate Reinhardt¹, Guntje Kneiseler², Hideo Baba³, Phillip Würzinger¹, Ursula Rauen⁴, Andreas Paul¹, Thomas Minor

¹General, Visceral and Transplantation Surgery, University Hospital Essen, Essen, Germany, ²Gastroenterology and Hepatology, University Hospital Essen, Essen, Germany, ³Pathology, University Hospital Essen, Essen, Germany, ⁴Institute of Pysiological Chemistry, University Duisburg-Essen, Essen, Germany, ⁵Surgical Research Division, University Clinic of Surgery, Bonn, Germany

Cold storage is still a major concern in liver transplantation. Previous animal studies pointed out better results for a modified Histidine-Tryptophan-Ketoglutarate solution (HTK) in heart, lung and kidney transplantation compared to previously used HTK. Aim of this study is to demonstrate safety and feasibility of the modified HTK solution in a large animal model.

20 female swine were randomized into two groups (n=10) each with 5 donors and 5 recipients. The solution used for each transplant was blinded and randomized to modified HTK and standard HTK as control group. Liver transplantations were performed with all anastomoses in an end-to-end fashion. Anesthesia was maintained by intravenous administration of fentanyl and propofol continuously. In each swine the observation period was 7 days, immunosuppression applied as cyclosporine A (8,5mg/kg BW/d) and prednisolone (500 mg intraoperative single dose).

Liver transplantations was performed after a mean cold ischemic time of 307±10 minutes. Mean warm ischemic time was 23.2±2.9 minutes. Mean total surgery time was 225±39 minutes. There were no significant differences in cold ischemic time (p=0,88), warm ischemic time (p=0,69),  time of surgery (p=0,98), donor weight (p=0,69) and recipient weight (p=0,81) between the both groups. All animals survived 7 days after operation, although one swine in the standard HTK group showed secondary dysfunction of the transplanted liver. Laboratory analysis demonstrated a tendency to improved liver function or less reperfusion injury, but no significant differences between the groups. On POD 7 the Quick´s value in the test group was 116.6±5.6 (control group 82.2±37.9; p=0.08); mean serum creatinine was 1.03±0.22 (control group 2.54±1.73; p=0.09). Partial thromboplastin time, serum bilirubin, alanine transaminase, cholinesterase and µ-GT were equal.

Orthotopic liver transplantations seems to be feasible and safe using the modified HTK solution due to first results of this in this large animal model. The advantages of the modified solution shown for other organs and in rat liver transplantation could not be reproduced, possibly due to the small number of animals in our study.Further evaluation in clinical setting seems to be justified to confirm the positive results shown in previous studies.