0041-1337/02/7407-944/0 TRANSPLANTATION Vol. 74, 944–951, No. 7, October 15, 2002 Copyright © 2002 by Lippincott Williams & Wilkins, Inc. Printed in U.S.A. FUNCTIONAL RECOVERY OF PRESERVED LIVERS FOLLOWING WARM ISCHEMIA: IMPROVEMENT BY MACHINE PERFUSION PRESERVATION CHARLES Y. LEE, 1 JIAN X. ZHANG, 2 JON W. JONES,JR., 3 JAMES H. SOUTHARD, 4 AND MARK G. CLEMENS 2 Background. Hypothermic machine perfusion pres- ervation has the potential to relieve the current donor shortage problem by reclaiming and preserving mar- ginal donor organs including those from viable non- heart-beating donors. A number of problems exist with the current machine perfusion technology for preserv- ing livers, and much research is needed to determine the clinical impact of this technology in preserving non-heart-beating donor livers. Methods. This study was conducted to compare the poststorage function and microcirculation of simple cold stored and machine perfusion preserved livers that had experienced 30 min of warm ischemia fol- lowed by a 10 hr preservation period. In an isolated rat liver perfusion model, lactate dehydrogenase activity, indocyanine green secretion, and portal pressure values were determined at major time points. An intravital mi- croscopy was conducted to assess microcirculation. Results. The results showed an increase in flow ho- mogeneity of machine perfused livers, which corre- lated with the reduction in portal pressure when com- pared with simple cold storage (5.40.4 vs. 8.70.6 mm Hg). A reduction in lactate dehydrogenase levels in the perfusate (33322 vs.1038 U/L) and an increase in bile production of the machine perfused livers (4.90.5 vs. 33.21.7 g/min/g liver) and indocyanine green se- cretion (11.71.7 vs. 21.22.1 Abs/g bile) were observed at all time points (meanSE of final point given). In- travital microscopic examination indicated that large regions of non flow, as indicated by the absence of fluorescein isothiocyanate-labeled albumin, were ob- served in the simple cold stored tissue, whereas machine perfused liver showed increase flow homogeneity. Val- ues of bile production, indocyanine secretion, and cellu- lar damages were comparable with controls. Histologic examination confirmed that simple cold stored tissue displayed increased vacuolization, and machine per- fused tissue showed regions of normal hepatic structure. Conclusion. These results suggest that machine per- fusion for 10 hr improves both poststorage function and microcirculation while reducing cellular damage of liver tissue that has experienced 30 min of warm ischemia, when compared with simple cold storage. Further studies need to be conducted, but this study suggests that machine perfusion preservation has the potential to reclaim and preserve liver tissues after warm ischemic insult. INTRODUCTION Given the ever-growing need for donor livers, extending the current donor criteria to include more non-heart-beating donors (NHBD) (1–3) has been suggested. Although this ex- tension would increase the number of donors available and transplantations performed, a number of problems exist with these donor organs. There are studies suggesting that trans- plantation of NHBD livers is feasible (4–6), but methods to reclaim and preserve these organs for general use in trans- plant centers remain unsatisfactory (7, 8). Two issues are associated with retrieval and preservation of NHBD livers. First, a preflush is needed to remove stag- nant blood following the period of warm noncirculatory isch- emia (9, 10). Several groups are investigating the optimal preflush solution and the protocol for organ retrieval and are assessing such factors as preflush temperature, viscosity, endothelin antagonists, and the use of plasminogen activa- tors (10 –13). Second, the method of storage needs to be im- proved for these tissues after the warm ischemic insult (7, 8). Currently, simple cold storage with the University of Wis- consin (UW) solution is used as the standard to assess pre- flush protocols (7, 8), but this method may not be optimal, as demonstrated by the experience in kidney preservation from NHBD (14, 15). Machine perfusion has been shown to improve preserva- tion of NHBD kidneys at several centers (14, 16, 17). In a recent report at the University Hospital of Maastricht, 70% of NHBD kidneys have been successfully transplanted (18). The concept of machine perfusion preservation in liver trans- plantation has not been successfully transferred (19). Ma- chine perfusion has not increased preservation time of stan- dard heart-beating donor livers; however, preliminary studies by two groups have recently suggested that machine perfusion can be used to reclaim and preserve, for short periods, NHBD livers (20, 21). No definitive consensus has been reached regarding this method, and more studies are needed to assess the potential of this method to reclaim and preserve NHBD livers. This article reports on improved pres- ervation of liver tissues after warm ischemic insult with machine perfusion. This study compares poststorage function and microcirculation after 10 hr of machine perfusion pres- This work was supported by a Whitaker Foundation Grant #RG- 00 – 0359, NIH Bioengineering Research Partnership Award NIDDK #DK58503, and NIDDK DK#38201. 1 Department of Mechanical Engineering and Engineering Sci- ence, University of North Carolina at Charlotte, Charlotte, North Carolina. 2 Department of Biology, University of North Carolina at Char- lotte, Charlotte, North Carolina. 3 Transplantation Center, Carolinas Medical Center, Charlotte, North Carolina. 4 Department of Surgery, University of Wisconsin-Madison Med- ical School, Madison, Wisconsin. Address correspondence to: Dr. Charles Y. Lee, 278 Smith, De- partment of Mechanical Engineering and Engineering Science, Uni- versity of North Carolina at Charlotte, 9201 University City Blvd, Charlotte, NC 28223. E-mail: cyclee@uncc.edu. Received 12 February 2001. Accepted 1 April 2002. 944 DOI: 10.1097/01.TP.0000026246.17635.67