May 2012, 1:6,
Open Access This content is freely available online to anyone, anywhere at any time.
Date: 09 May 2012
A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation
Liver donor shortages stimulate the development of strategies that incorporate damaged organs into the donor pool. Herein we present a simplified machine perfusion system without the need for oxygen carriers or temperature control, which we validated in a model of orthotopic liver transplantation.
Rat livers were procured and subnormothermically perfused with supplemented Williams E medium for 3 hours, then transplanted into healthy recipients (Fresh-SNMP group). Outcome was compared with static cold stored organs (UW-Control group). In addition, a rat liver model of donation after cardiac death was adapted using a 60-minute warm ischemic period, after which the grafts were either transplanted directly (WI group) or subnormothermically perfused and transplanted (WI-SNMP group).
One-month survival was 100% in the Fresh-SNMP and UW-Control groups, 83.3% in the WI-SNMP group and 0% in the WI group. Clinical parameters, postoperative blood work and histology did not differ significantly between survivors.
This work demonstrates for the first time in an orthotopic transplantation model that ischemically damaged livers can be regenerated effectively using practical subnormothermic machine perfusion without oxygen carriers.
Human Resources and Services AdministrationOrgan Procurement and Transplantation Network and the Scientific Registry of Transplant Recipients: 2009 OPTN/SRTR Annual Report: Transplant Data 1999–2008 [http://optn.transplant.hrsa.gov/ar2009/]
Schleifer D: A simple heart-lung machine for the perfusion of small laboratory animals and for organ perfusion] [in German. Chirurg 1967, 38:477–480.PubMed
Vogel T, Brockmann JG, Friend PJ: Ex-vivo normothermic liver perfusion: an update. Curr Opin Organ Transplant 2011, 15:167–172.CrossRef
Perkins JD: Defatting the fatty liver with normothermic perfusion of the liver allograft. Liver Transpl 2009, 15:1366–1367.PubMed
Mann CD, Metcalfe MS, Nicholson ML: Normothermic perfusion of ischaemic porcine kidneys: an evaluation of ex vivo function and endothelin receptor antagonism. J Nephrol 2009, 22:144–151.PubMed
Uygun K, Tolboom H, Izamis ML, Uygun B, Sharma N, Yagi H, Soto-Gutierrez A, Hertl M, Berthiaume F, Yarmush ML: Diluted blood reperfusion as a model for transplantation of ischemic rat livers: alanine aminotransferase is a direct indicator of viability. Transplant Proc 2010, 42:2463–2467.PubMedCrossRef
Hellinger A, Fiegen R, Lange R, Rauen U, Schmidt U, Hirche H, Kaiser S, de Groot H, Erhard J, Eigler FW: Preservation of pig liver allografts after warm ischemia: normothermic perfusion versus cold storage. Langenbecks Arch Chir 1997, 382:175–184.PubMed
Filipponi F, Bacci S, Romagnoli P: Normothermic liver perfusion ex situ: a resuscitation tool for hepatic grafts damaged by warm ischemia. G Chir 1993, 14:254–258.PubMed
Bond M, Pitt M, Akoh J, Moxham T, Hoyle M, Anderson R: The effectiveness and cost-effectiveness of methods of storing donated kidneys from deceased donors: a systematic review and economic model. Health Technol Assess 2009, 13:iii-iv, xi-xiv, 1–156.
Matias JE, Morais FA, Kato DM, Koziak V, Brioschi ML, Tambara EM, Agulham MÂ, Coelho JC: Prevention of normothermic hepatic ischemia during in situ liver perfusion with three different preservation solutions: experimental analysis by realtime infrared radiation thermography] [in Portuguese. Rev Col Bras Cir 2010, 37:211–217.PubMedCrossRef
Plauth M, Zimmermann B, Raible A, Vieillard-Baron D, Bauder-Gross D, Hartmann F: Use of an artificial oxygen carrier in isolated rat liver perfusion: first demonstration of net glucose uptake at physiological portal glucose concentrations using a hemoglobin-free perfusate. Res Exp Med (Berl) 1991, 191:339–347.CrossRef
Tolboom H, Izamis ML, Sharma N, Milwid JM, Uygun B, Berthiaume F, Uygun K, Yarmush ML: Subnormothermic machine perfusion at both 20°C and 30°C recovers ischemic rat livers for successful transplantation. J Surg Res in press
Muriel A, López V, Zamora Vincente J, Gutiérrez C, Abraira Santos V, Hernández Marrero D: [Does hypothermic machine perfusion provide an advantage over cold storage in the incidence rate of delayed graft function following a deceased-donor kidney transplant?] [in Spanish]. Nefrologia 2009,29(6 Suppl):85–87.PubMed
Olschewski P, Gass P, Ariyakhagorn V, Jasse K, Hunold G, Menzel M, Schöning W, Schmitz V, Neuhaus P, Puhl G: The influence of storage temperature during machine perfusion on preservation quality of marginal donor livers. Cryobiology 2011, 60:337–343.CrossRef
- A simplified subnormothermic machine perfusion system restores ischemically damaged liver grafts in a rat model of orthotopic liver transplantation
- Open Access
- Available under Open Access This content is freely available online to anyone, anywhere at any time.
- Online Date
- May 2012
- Online ISSN
- BioMed Central
- Additional Links
- Author Affiliations
- 1. Center for Engineering in Medicine/Surgical Services, Massachusetts General Hospital, Harvard Medical School, and Shriners Burns Hospital, 51 Blossom Street, Boston, MA, 02114, USA
- 2. Department of Biomedical Engineering, Rutgers University, 599 Taylor Road, Piscataway, NJ, 08854, USA