title: Functional recovery of preserved livers following warm ischemia: improvement by machine perfusion preservation.
abstract: BACKGROUND
  Hypothermic machine perfusion preservation has the potential to relieve the current donor shortage problem by reclaiming and preserving marginal donor organs including those from viable non-heart-beating donors. A number of problems exist with the current machine perfusion technology for preserving 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 followed 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 microscopy was conducted to assess microcirculation.
  
  
  RESULTS
  The results showed an increase in flow homogeneity of machine perfused livers, which correlated with the reduction in portal pressure when compared 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 microg/min/g liver) and indocyanine green secretion (11.7+/-1.7 vs. 21.2+/-2.1 Abs/g bile) were observed at all time points (mean+/-SE of final point given). Intravital microscopic examination indicated that large regions of non flow, as indicated by the absence of fluorescein isothiocyanate-labeled albumin, were observed in the simple cold stored tissue, whereas machine perfused liver showed increase flow homogeneity. Values of bile production, indocyanine secretion, and cellular damages were comparable with controls. Histologic examination confirmed that simple cold stored tissue displayed increased vacuolization, and machine perfused tissue showed regions of normal hepatic structure.
  
  
  CONCLUSIONS
  These results suggest that machine perfusion 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.
authors.affiliation: Department of Mechanical Engineering and Engineering Science, University of North Carolina at Charlotte, Charlotte, North Carolina 28223, USA. cyclee@uncc.edu
authors.forename: Charles Y
authors.initials: CY
authors.lastname: Lee
authors.forename: Jian X
authors.initials: JX
authors.lastname: Zhang
authors.forename: Jon W
authors.initials: JW
authors.lastname: Jones
authors.forename: James H
authors.initials: JH
authors.lastname: Southard
authors.forename: Mark G
authors.initials: MG
authors.lastname: Clemens
mesh_terms: D000818:Animals; D004396:Coloring Agents; D015925:Cryopreservation; D004867:Equipment Design; D006358:Hot Temperature; D066298:In Vitro Techniques; D007208:Indocyanine Green; D007511:Ischemia / Q000473:pathology / Q000503:physiopathology*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008099:Liver / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology*; D008102:Liver Circulation; D008297:Male; D008833:Microcirculation; D009926:Organ Preservation / Q000379:methods*; D010477:Perfusion / Q000295:instrumentation* / Q000379:methods*; D011169:Portal Vein / Q000503:physiopathology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors; D014690:Venous Pressure
chemical_list: D004396:Coloring Agents; D007770:L-Lactate Dehydrogenase; D007208:Indocyanine Green