Reply to: “The rescue of DCD rodent livers grafts: Is there HOPE?”
Authors: Andrea Schlegel, Philipp Dutkowski, Pierre-Alain Clavien
Journal: Journal of Hepatology (2014)

The rescue of DCD rodent livers grafts: Is there HOPE?Journal of HepatologyVol. 62Issue 3PreviewIt is with great interest that we have read the article of Schlegel et al. [1] on normothermic machine perfusion (NMP) vs. hypothermic oxygenated perfusion (HOPE) to rescue rodent liver grafts, suffering from extended warm ischemia. In this study, a comparison was made between the ability of NMP and HOPE to rescue DCD rodent liver grafts with prolonged warm ischemia of 30 and 60 min. Grafts were subjected to ex vivo reperfusion using an isolated perfused rat liver model (IPRL) and orthotopic liver transplantation (OLT). Full-Text PDF Open AccessWarm vs. cold perfusion techniques to rescue rodent liver graftsJournal of HepatologyVol. 61Issue 6PreviewA variety of liver perfusion techniques have been proposed to protect liver grafts prior to implantation. We compared hypothermic and normothermic oxygenated perfusion techniques in a rat liver transplant model, using higher risk grafts obtained after cardiac arrest (DCD). Full-Text PDF We read with great interest the letter by Kopp et al. regarding our study on machine perfusion of rat livers, donated after cardiac death (DCD). Our goal was to compare the two main liver perfusion techniques, normothermic (NMP) and hypothermic oxygenated perfusion (HOPE) in terms of liver function and injury in a transplant model, closely adapted to the clinical situation [[1]Schlegel A. Kron P. Graf R. Dutkowski P. Clavien P.A. Warm vs. cold perfusion technique to rescue rodent liver grafts.J Hepatol. 2014; 61: 1267-1275Abstract Full Text Full Text PDF PubMed Scopus (115) Google Scholar]. We are pleased to discuss the points raised by the letter from the Leiden’s group. The first question targets on the perfusate composition used in the normothermic experiments. We have carefully chosen a perfusate for NMP experiments that is closely adapted to current leaders in the field. For normothermic perfusion experiments with diluted blood, we used a perfusate described by the group of Peter Friend [[2]Brockmann J. Reddy S. Coussios C. Pigott D. Guirriero D. Hughes D. et al.Normothermic perfusion: a new paradigm for organ preservation.Ann Surg. 2009; 250: 1-6Crossref PubMed Scopus (243) Google Scholar], who demonstrated very recently the first worldwide application of normothermic oxygenated perfusion in twenty human livers (reported at the WTC 2014, San Francisco). Second, for experiments with a leukocyte and platelet-depleted perfusate, we used the perfusate described by the group of Robert Porte [[3]Op den Dries S. Karimian N. Sutton M.E. Westerkamp A.C. Nijsten M.W. Gouw A.S. et al.Ex vivo normothermic machine perfusion and viability testing of discarded human donor livers.Am J Transplant. 2013; 13: 1327-1335Crossref PubMed Scopus (218) Google Scholar]. Both groups report a haematocrit of approximately 20%, insulin, heparin and nutritions were similarly as in our experiments. Adding of Williams E medium in normothermic experiments is based on recent experiments by Op den Dries et al. in rats [[4]Op den Dries, Karimian N, Sutton ME, Kuipers M, Wiersema-Buist J, Ottens PJ, et al. Machine perfusion reduces Bile duct injury and improves biliary epithelial function in rat donor livers, in Studies on etiology and the protective Role of machine perfusion, Chapter 9, page 128–146 [Ph.D. thesis]; 2013, submitted for publication.Google Scholar]. Both perfusates have been tested initially in healthy normal rat livers (no injury group) and achieved minimal AST release, sufficient bile flow, tissue ATP and 100% animal survival, thus demonstrating sufficient energy supply during normothermic perfusion experiments (Fig. 1). The second question is on oxygen levels during normothermic perfusion. Op den Dries et al. reported 50–70 kPa for human livers, while Brockmann et al. perfused with 15–20 kPa. We perfused rat livers with 50 kPa, as oxygen measurements at the liver outflow confirmed by far sufficient oxygenation in all experiments with this degree of oxygenation, also demonstrated by stable pH and lactate (Supplementary Fig. 1). The third question targets on the different perfusion routes in HOPE and in normothermic experiments (portal vein only vs. dual perfusion). We have also performed normothermic perfusion in rat livers (no injury and DCD) through the portal vein only. These grafts were compared to dually perfused rat livers and showed a comparable amount of injury in terms of AST release, pH, lactate and bile production (Supplementary Fig. 1). In addition, as healthy controls demonstrated good function after normothermic dual perfusion and transplantation, we assume no increased injury by the dual perfusion technique. Finally, we would like to state that all livers were flushed with UW solution after initial flush with heparinized saline (see Materials and methods). In summary, we would like to thank the authors for their valuable questions and comments. We agree that human trials are needed to discover the impact of both machine perfusion techniques. We have recently initiated a multicentre randomized trial on HOPE for human livers transplants, donated after brain death (DBD) (www.hope-liver.com). The authors declared that they do not have anything to disclose regarding funding or conflict of interest with respect to this manuscript. 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