Advertisement
The hand surgery landscape| Volume 42, ISSUE 12, P1019-1024, December 2017

Download started.

Ok

Strategies to Reduce Ischemia Reperfusion Injury in Vascularized Composite Allotransplantation of the Limb

  • Kavit R. Amin
    Correspondence
    Corresponding author: Kavit R. Amin, MBBS, The Manchester Collaborative Centre for Inflammation Research, University of Manchester, UK.
    Affiliations
    The Manchester Collaborative Centre for Inflammation Research, University Hospital of South Manchester, Manchester, UK

    The Transplant Centre, University Hospital of South Manchester, Manchester, UK

    Blond McIndoe Laboratories, University of Manchester, University Hospital of South Manchester, Manchester, UK

    Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK
    Search for articles by this author
  • Jason K.F. Wong
    Affiliations
    Blond McIndoe Laboratories, University of Manchester, University Hospital of South Manchester, Manchester, UK

    Department of Plastic Surgery, University Hospital of South Manchester, Manchester, UK
    Search for articles by this author
  • James E. Fildes
    Affiliations
    The Manchester Collaborative Centre for Inflammation Research, University Hospital of South Manchester, Manchester, UK

    The Transplant Centre, University Hospital of South Manchester, Manchester, UK
    Search for articles by this author
Published:October 18, 2017DOI:https://doi.org/10.1016/j.jhsa.2017.09.013
      An important and often underinvestigated contributor to solid organ transplant rejection is ischemia reperfusion injury. This pathophysiological response releases damaging reactive oxygen species and cell stress signals that initiate inflammation, which has a critical role in priming the immune system for allorecognition. In time, this renders graft dysfunction and how this response is mediated in composite tissues remains unknown. Current protocols are drawn from solid organ transplantation with little scientific basis as to how this informs current hand transplantation practices. In addition to preservation flush and allograft cooling, machine perfusion is placing itself experimentally as a concept that could act to promote viability and increase the critical ischemic window, which is especially beneficial at a time of limited donors. With the increasing prevalence worldwide of hand transplantation, we review the potential contribution of ischemia reperfusion injury to hand allograft rejection including both current and experimental strategies.

      Key words

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Journal of Hand Surgery
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Win T.S.
        • Henderson J.
        Management of traumatic amputations of the upper limb.
        BMJ. 2014; 348: g255
        • Ziegler-Graham K.
        • MacKenzie E.J.
        • Ephraim P.L.
        • Travison T.G.
        • Brookmeyer R.
        Estimating the prevalence of limb loss in the United States: 2005 to 2050.
        Arch Phys Med Rehabil. 2008; 89: 422-429
        • McLaren A.J.
        • Friend P.J.
        Trends in organ preservation.
        Transpl Int. 2003; 16: 701-708
        • Pradka S.P.
        • Ong Y.S.
        • Zhang Y.
        • et al.
        Increased signs of acute rejection with ischemic time in a rat musculocutaneous allotransplant model.
        Transplant Proc. 2009; 41: 531-536
        • Collard C.D.
        • Gelman S.
        Pathophysiology, clinical manifestations, and prevention of ischemia-reperfusion injury.
        Anesthesiology. 2001; 94: 1133-1138
        • Maxwell S.R.
        • Lip G.Y.
        Reperfusion injury: a review of the pathophysiology, clinical manifestations and therapeutic options.
        Int J Cardiol. 1997; 58: 95-117
        • Halloran P.F.
        • Homik J.
        • Goes N.
        • et al.
        The “injury response”: a concept linking nonspecific injury, acute rejection, and long-term transplant outcomes.
        Transplant Proc. 1997; 29: 79-81
        • Dubernard J.M.
        • Owen E.
        • Lefrancois N.
        • et al.
        First human hand transplantation. Case report.
        Transpl Int. 2000; 13: S521-S524
        • Iijima Y.
        • Ajiki T.
        • Teratani T.
        • Hoshino Y.
        • Kobayashi E.
        Muscle is a target for preservation in a rat limb replantation model.
        Plast Reconstr Surg Glob Open. 2013; 1: e70
        • Hautz T.
        • Hickethier T.
        • Blumer M.J.
        • et al.
        Histomorphometric evaluation of ischemia-reperfusion injury and the effect of preservation solutions histidine-tryptophan-ketoglutarate and University of Wisconsin in limb transplantation.
        Transplantation. 2014; 98: 713-720
        • Wight J.
        • Chilcott J.
        • Holmes M.
        • Brewer N.
        The clinical and cost-effectiveness of pulsatile machine perfusion versus cold storage of kidneys for transplantation retrieved from heart-beating and non-heart-beating donors.
        Health Technol Assess. 2003; 7: 1-94
        • Gordon L.
        • Levinsohn D.G.
        • Borowsky C.D.
        • et al.
        Improved preservation of skeletal muscle in amputated limbs using pulsatile hypothermic perfusion with University of Wisconsin solution. A preliminary study.
        J Bone Joint Surg Am. 1992; 74: 1358-1366
        • Langer V.
        Management of major limb injuries.
        ScientificWorldJournal. 2014; 2014: 640430
        • Landin L.
        • Cavadas P.C.
        • Garcia-Cosmes P.
        • Thione A.
        • Vera-Sempere F.
        Perioperative ischemic injury and fibrotic degeneration of muscle in a forearm allograft: functional follow-up at 32 months post transplantation.
        Ann Plast Surg. 2011; 66: 202-209
        • Herzberg G.
        • Weppe F.
        • Masson N.
        • Gueffier X.
        • Erhard L.
        Clinical evaluation of two bilateral hand allotransplantations at six and three years follow-up.
        Chir Main. 2008; 27: 109-117
        • Zhao Y.
        • Feng Q.
        • Huang Z.
        • et al.
        Simvastatin inhibits inflammation in ischemia-reperfusion injury.
        Inflammation. 2014; 37: 1865-1875
        • Fox-Robichaud A.
        • Payne D.
        • Hasan S.U.
        • et al.
        Inhaled NO as a viable antiadhesive therapy for ischemia/reperfusion injury of distal microvascular beds.
        J Clin Invest. 1998; 101: 2497-2505
        • Villamaria C.Y.
        • Fries C.A.
        • Spencer J.R.
        • Roth M.
        • Davis M.R.
        Hydrogen sulfide mitigates reperfusion injury in a porcine model of vascularized composite autotransplantation.
        Ann Plast Surg. 2014; 72: 594-598
        • Nakao A.
        • Toyokawa H.
        • Abe M.
        • et al.
        Heart allograft protection with low-dose carbon monoxide inhalation: effects on inflammatory mediators and alloreactive T-cell responses.
        Transplantation. 2006; 81: 220-230
        • Snijder P.M.
        • van den Berg E.
        • Whiteman M.
        • Bakker S.J.
        • Leuvenink H.G.
        • van Goor H.
        Emerging role of gasotransmitters in renal transplantation.
        Am J Transplant. 2013; 13: 3067-3075
        • Wang L.C.
        • Lawson S.D.
        • Fries C.A.
        • Davis M.R.
        Hyperbaric sub-normothermic ex-vivo perfusion delays the onset of acute rejection in a porcine VCA model.
        Plast Reconstr Surg. 2015; 136: 34
        • Cooley B.C.
        • Tadych K.L.
        • Gould J.S.
        Perfusion of free flaps with heparinized whole blood during ischemic storage.
        J Reconstr Microsurg. 1990; 6: 49-53
        • Hobson II, R.W.
        • Neville R.
        • Watanabe B.
        • Canady J.
        • Wright J.G.
        • Belkin M.
        Role of heparin in reducing skeletal muscle infarction in ischemia-reperfusion.
        Microcirc Endothelium Lymphatics. 1989; 5: 259-276
        • Mohan C.
        • Gennaro M.
        • Marini C.
        • Ascer E.
        Reduction of the extent of ischemic skeletal muscle necrosis by perfusion with oxygenated perfluorocarbon.
        Am J Surg. 1992; 164: 194-198
        • Kalogeris T.
        • Baines C.P.
        • Krenz M.
        • Korthuis R.J.
        Cell biology of ischemia/reperfusion injury.
        Int Rev Cell Mol Biol. 2012; 298: 229-317
        • Guibert E.E.
        • Petrenko A.Y.
        • Balaban C.L.
        • Somov A.Y.
        • Rodriguez J.V.
        • Fuller B.J.
        Organ preservation: current concepts and new strategies for the next decade.
        Transfus Med Hemother. 2011; 38: 125-142
        • Gracia-Sancho J.
        • Villarreal Jr., G.
        • Zhang Y.
        • et al.
        Flow cessation triggers endothelial dysfunction during organ cold storage conditions: strategies for pharmacologic intervention.
        Transplantation. 2010; 90: 142-149
        • Ozer K.
        • Rojas-Pena A.
        • Mendias C.L.
        • Bryner B.S.
        • Toomasian C.
        • Bartlett R.H.
        The effect of ex situ perfusion in a swine limb vascularized composite tissue allograft on survival up to 24 hours.
        J Hand Surg Am. 2016; 41: 3-12
        • Muller S.
        • Constantinescu M.A.
        • Kiermeir D.M.
        • et al.
        Ischemia/reperfusion injury of porcine limbs after extracorporeal perfusion.
        J Surg Res. 2013; 181: 170-182
        • Munoz M.
        • Slappendel R.
        • Thomas D.
        Laboratory characteristics and clinical utility of post-operative cell salvage: washed or unwashed blood transfusion?.
        Blood Transfus. 2011; 9: 248-261
        • Steen S.
        • Liao Q.
        • Wierup P.N.
        • Bolys R.
        • Pierre L.
        • Sjoberg T.
        Transplantation of lungs from non-heart-beating donors after functional assessment ex vivo.
        Ann Thorac Surg. 2003; 76 (discussion 252): 244-252
        • Constantinescu M.A.
        • Knall E.
        • Xu X.
        • et al.
        Preservation of amputated extremities by extracorporeal blood perfusion; a feasibility study in a porcine model.
        J Surg Res. 2011; 171: 291-299
        • Bing R.J.
        Lindbergh and the biological sciences (a personal reminiscence).
        Tex Heart Inst J. 1987; 14: 230-237
        • Lapchinsky A.G.
        Recent results of experimental transplantation of preserved limbs and kidneys and possible use of this technique in clinical practice.
        Ann N Y Acad Sci. 1960; 87: 539-571
        • Kueckelhaus M.
        • Fischer S.
        • Sisk G.
        • et al.
        A mobile extracorporeal extremity salvage system for replantation and transplantation.
        Ann Plast Surg. 2016; 76: 355-360