BACKGROUND: Following pig to primate kidney transplantation, xenogenic activation of the coagulation (XAC) system of the recipient eventually leading to organ dysfunction and disseminated intravascular coagulation (DIC) can be observed. METHODS: Using an ex-vivo perfusion circuit based on low-dose heparin-mediated anticoagulation and exogenous complement inhibition by C1- Inhibitor (C1-Inh), we have analysed XAC following contact of human blood with porcine endothelium. Porcine kidneys (n = 23) were recovered following in situ cold perfusion with histidine-tryptophan-ketoglutarate (HTK) solution and were connected to a perfusion circuit utilizing freshly drawn pooled human AB blood. RESULTS: Kidney survival during organ perfusion with human blood, CI-Inh, heparin but without any further pharmacological intervention was 126 +/- 78 min. XAC was observed with significantly elevated levels of D-dimer and thrombin antithrombin complexes (TAT). Pharmacological intervention with nitroprusside and prostacycline resulted in increased organ survival (220 +/- 28 min and 180 +/- 85 min respectively) but failed to inhibit XAC. In contrast, addition of activated protein C (APC) significantly reduced the increase in D-dimer and TAT and prolonged organ survival to 240 min (+/-0). On histology, no remarkable signs of XAC were observed. CONCLUSIONS: We conclude that exogenous APC is able to reduce XAC in this ex vivo perfusion model.
BACKGROUND: Following pig to primate kidney transplantation, xenogenic activation of the coagulation (XAC) system of the recipient eventually leading to organ dysfunction and disseminated intravascular coagulation (DIC) can be observed. METHODS: Using an ex-vivo perfusion circuit based on low-dose heparin-mediated anticoagulation and exogenous complement inhibition by C1- Inhibitor (C1-Inh), we have analysed XAC following contact of human blood with porcine endothelium. Porcine kidneys (n = 23) were recovered following in situ cold perfusion with histidine-tryptophan-ketoglutarate (HTK) solution and were connected to a perfusion circuit utilizing freshly drawn pooled human AB blood. RESULTS: Kidney survival during organ perfusion with human blood, CI-Inh, heparin but without any further pharmacological intervention was 126 +/- 78 min. XAC was observed with significantly elevated levels of D-dimer and thrombin antithrombin complexes (TAT). Pharmacological intervention with nitroprusside and prostacycline resulted in increased organ survival (220 +/- 28 min and 180 +/- 85 min respectively) but failed to inhibit XAC. In contrast, addition of activated protein C (APC) significantly reduced the increase in D-dimer and TAT and prolonged organ survival to 240 min (+/-0). On histology, no remarkable signs of XAC were observed. CONCLUSIONS: We conclude that exogenous APC is able to reduce XAC in this ex vivo perfusion model.
Authors: Hellen E Ahrens; Björn Petersen; Wolf Ramackers; Stoyan Petkov; Doris Herrmann; Janet Hauschild-Quintern; Andrea Lucas-Hahn; Petra Hassel; Maren Ziegler; Wiebke Baars; Sabine Bergmann; Reinhard Schwinzer; Michael Winkler; Heiner Niemann Journal: Transplant Direct Date: 2015-07-28