B. Banan1, H. Chung1, Z. Xiao1, Y. Tarabishy1, P. Manning2, D. McGraw2, G. Upadhya1, T. Mohanakumar1, Y. Lin1, W. C. Chapman1 1Washington University School Of Medicine In St. Louis,Trasnplant/Surgery/Medicine,St. Louis, MO, USA 2Vasculox, Inc,St. Louis, MO, USA
Introduction: A critical shortage of donor livers has led to increased efforts to expand the criteria for suitable donors. However, the higher sensitivity of extended criteria livers to ischemia reperfusion injury (IRI) is a major obstacle in organ cold preservation which jeopardizes post-transplant graft viability. Normothermic extracorporeal liver perfusion (NELP) has been investigated to reduce ischemic damage, restore physiologic function and enable surgeons to assess viability of the liver prior to transplant. The goal of this study was to investigate the efficacy of NELP to re-establish physiologic parameters and metabolic functions in livers procured after an extended warm ischemia time (WIT) in a porcine model. We for the first time compared physiological parameters of livers maintained continuously on NELP to ones which preserved in cold solution.
Methods: Livers from 9 female landrace pigs (30-34kg) were subjected to 20 min (WIT-20 group, n=3), 40 min (WIT-40 group, n=3) and 60 min (WIT-60 group, n=3) warm ischemia followed by 8 hours of NELP. To assess superiority of NELP over cold storage, WIT-40 group was compared to three livers subjected to 40 min warm ischemia time followed by 6 hours of cold storage (WCIT-40 group) in HTK solution and 2 hours of NELP. Blood samples and biopsies were taken at hourly intervals. We considered the final 2-hours of NELP as the test phase in all groups (ie, functional reperfusion period) for comparison purposes. Groups were compared using 2-way ANOVA test, with p<0.05 as significant.
Results: NELP stabilized transaminases and total bilirubin levels in all WIT groups. This was accompanied by significant improvement in bile and albumin production, and a remarkable decline in lactate and INR values. pH, Na+, K+, cl-, pCO2, bicarbonate and glucose measures were stabilized at physiologic levels. Oxygen extraction ratio was recovered in all WIT groups during first 30 minutes of machine perfusion and maintained until the end of study. Pathology review showed significant improvement from 0 hour (mild to moderate sinusoidal dilation and zone 3 necrosis) to end time of the NELP run (minimal hepatocyte necrosis and mild IRI) in all WIT study groups. WIT-40 and WCIT-40 comparison revealed significantly higher values of bile production, albumin and oxygen extraction ratio in WIT-40. However, WCIT-40 group showed higher AST, ALT, lactate and INR levels accompanied by moderate IRI. The following table summarizes some significant results obtained at the end of NELP run.
Conclusion: NELP improves and maintains metabolic and functional parameters of livers with either short or extended warm ischemia times and reduces IRI when compared to livers subjected to cold ischemia time.
