Downloaded from http://journals.lww.com/transplantjournal by BhDMf5ePHKbH4TTImqenVAHxkFJp/XpPk1L/H3vMGwqMxG9jwOd8eJPG+b4DlKuAX44qu/vwzmc= on 07/29/2018 Hypothermic Oxygenated Machine Perfusion in Porcine Donation After Circulatory Determination of Death Liver Transplant Constantino Fondevila, 1,4 Amelia J. Hessheimer, 1 Mark-Hugo J. Maathuis, 2 Javier Mun ˜oz, 1 Pilar Taura ´, 1 David Calatayud, 1 Henri Leuvenink, 2 Antoni Rimola, 1 Juan C. Garcı ´a-Valdecasas, 1 and Rutger J. Ploeg 3 Background. Livers from donation after circulatory determination-of-death (DCD) donors suffer ischemic injury during a preextraction period of cardiac arrest and are infrequently used for transplantation; they have the potential, however, to considerably expand the donor pool. We aimed to determine whether hypothermic oxygenated machine perfusion would improve or further deteriorate the quality of these livers using a clinically relevant porcine model. Methods. Donor livers were subjected to 90 min of cardiac arrest and preserved at 4-C with either static cold storage using University of Wisconsin solution (CS, n=6) or oxygenated machine perfusion using University of Wisconsin machine perfusion solution and 25% physiological perfusion pressures (HMP, n=5). After 4 hr of preservation, livers were transplanted into recipient pigs, which were followed intensively for up to 5 days. Results. Five-day survival was 0 in CS and 20% in HMP. Immediately after reperfusion, hepatocellular injury and function were improved in HMP versus CS. However, HMP grafts also demonstrated significant endothelial and Kupffer cell injury, and a progressive lesion developed 24 to 48 hr after reperfusion that led to death in all but one of the recipient animals. Conclusions. Although hypothermic oxygenated machine perfusion performed using subphysiological perfusion pressures seems to offer some advantages over cold storage in the preservation of ischemically damaged livers, it simultaneously conditions endothelial and Kupffer cell injury that may ultimately lead to the failure of these grafts. Keywords: Liver transplant, Donation after cardiac death, Marginal liver, Cold storage, Hypothermic perfusion. (Transplantation 2012;94: 22Y29) D onation after circulatory determination-of-death (DCD) donors have significant potential to expand the donor pool. The ischemic injury they suffer during cardiac arrest (CA) increases the risk for immediate and delayed graft complications (1Y3), however, and their livers are infrequently recovered. A primary factor limiting the broader clinical ap- plication of DCD liver transplantation is that cold storage (CS) inadequately maintains graft viability. Using CS merely slows organ degradation during ischemia. Machine perfusion, in contrast, delivers metabolic substrates, eliminates toxins, and may help revert preextraction injury and prevent further damage from developing. The conditions under which ma- chine perfusion should be performed, however, are debated. The logic behind using oxygenated hypothermic ma- chine perfusion (HMP) is that mitochondrial electron transport and oxidative energy production continue at low temperatures (4Y6), and HMP provides a continuous oxy- gen supply for adenosine triphosphate production during preservation (7). From a logistical standpoint, HMP is relatively easier to perform. Unlike normothermic machine perfusion (NMP), it does not require a heat exchanger or Research was supported by FIS Grant PI050610, Instituto de Salud Carlos III, Spain. A.J.H. was supported by the Fundacio ´ n BBVA, the Vanderbilt Medical School Medical Scholars Program, and the Fundacio ´ Catalana de Trasplantament. M.-H.J.M. was supported by a Novartis Study Grant from the European Society for Organ Transplantation. CIBERehd is funded by Instituto de Salud Carlos III, Spain. The authors declare no conflicts of interest. 1 Currently, Liver Transplant Unit, Institut de Malaties Digestives, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, Barcelona, Spain. 2 Currently, Surgical Research Laboratory, Department of Surgery, University Medical Center Groningen, Groningen, the Netherlands. 3 Currently, Nuffield Department of Surgical Sciences, Oxford Transplant Centre, Churchill Hospital, Headington, Oxford, United Kingdom; formerly, Surgical Research Laboratory, Department of Surgery, Uni- versity Medical Center Groningen, University of Groningen, Groningen, the Netherlands. 4 Address correspondence to: Constantino Fondevila, MD, PhD, Liver Transplant Unit, Department of Surgery, Hospital Clı ´nic, University of Barcelona, C/ Villarroel 170, 08036 Barcelona, Spain. E-mail: cfonde@clinic.ub.es Received 7 February 2012. Revision requested 27 February 2012. Accepted 26 March 2012. C.F., A.J.H., and M.-H.J.M. designed the study. C.F., A.J.H., M.-H.J.M., J.M., P.T., and D.C. performed the research. C.F., A.J.H., J.M., and H.L. an- alyzed the data. C.F. and A.J.H. wrote the article. A.R., J.C.G.-V., and R.J.P. critically revised and approved the article. Copyright * 2012 by Lippincott Williams & Wilkins ISSN: 0041-1337/12/9401-22 DOI: 10.1097/TP.0b013e31825774d7 CLINICAL AND TRANSLATIONAL RESEARCH 22 www.transplantjournal.com Transplantation & Volume 94, Number 1, July 15, 2012 Copyright © 2012 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.