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Abstract

Objectives: Iloprost has the potential to protect the liver transplant graft before and during cold ischemia. We studied iloprost administration during organ procurement and reperfusion in an extracorporeal pig liver perfusion model. Materials and Methods: German Landrace pigs (n = 7/group; 22-26 kg each) were used as donors. Preservation was performed by aortic perfusion with 2L Bretschneiders' Histidine-Tryptophan-Ketoglutarate solution HTK and cold ischemia time (4°C) 20 hours followed by normothermic extracorporeal perfusion for 8 hours. Untreated controls (1) were compared to iloprost (2) donor bolus-treatment (1 μg/kg body weight), (3) addition of iloprost to Bretschneiders´ Histidine-Tryptophan-Ketoglutarate solution HTK (0.0125 μg/mL), (4) continuous infusion during reperfusion (2 ng/kg/min), and (5) combined treatment (2) and (4). Results: Iloprost donor treatment led to significantly higher bile production. Addition of iloprost to the preservation solution significantly improved hepatic artery perfusion and was accompanied by improvements of microcirculation and bile production. Iloprost reperfusion treatment alone significantly improved bile production. Enzyme levels were positively affected by all treatment regimens.Combined use of iloprost before and after ischemia improved hepatic artery flow and microcirculation and showed significantly lower hypoxia staining versus controls. Conclusions: Iloprost donor treatment and use of iloprost in the preservation solution significantly improved graft perfusion and function. The effects of graft treatment seemed greater before than after reperfusion. Combined treatment did not reveal a synergistic advantage. Key words: End-stage liver disease, Graft, Prostaglandin, Transplant IntroductionThe use of iloprost clinically and experimentally is widely accepted after liver transplant. 1-4 However, although beneficial clinically and experimentally, its use in donor pretreatment is uncommon and the exact recommendations about type of application are pending. [5][6][7] The purpose of this study was to compare 4 different iloprost treatment regimens to a control group and to determine their effect on liver injury and function after extended cold ischemia time (CIT) (20 h) in an isolated 8-hour extracorporeal pig liver perfusion model. The following parameters were assessed:• Liver perfusion (macro-and microcirculation). Materials and Methods Animals and anesthesiaGerman Landrace pigs aged 10 to 16 weeks with a mean body weight (BW) 23.7 ± 1.56 kg (range, 22-26 kg) were used as organ donors. Animals were purchased (Fa. Sommerfeld, Brandenburg, Germany) and housed in our animal facility located at Charité Campus Virchow Klinikum, Berlin, Germany, approximately 1 week before each experiment. Animals were examined after delivery and kept species-appropriate with free access to water. Twice daily they were fed with standard pig nutrition pellets (Mpig-H, Sniff Spezialitäten GmbH, Soest, Germany) and housed at a day and night cycle of 12 hours and mean temperature ...