title: Ex Situ Perfusion of Human Limb Allografts for 24 Hours.
abstract: BACKGROUND
  Vascularized composite allografts, particularly hand and forearm, have limited ischemic tolerance after procurement. In bilateral hand transplantations, this demands a 2 team approach and expedited transfer of the allograft, limiting the recovery to a small geographic area. Ex situ perfusion may be an alternative allograft preservation method to extend allograft survival time. This is a short report of 5 human limbs maintained for 24 hours with ex situ perfusion.
  
  
  METHODS
  Upper limbs were procured from brain-dead organ donors. Following recovery, the brachial artery was cannulated and flushed with 10 000 U of heparin. The limb was then attached to a custom-made, near-normothermic (30-33°C) ex situ perfusion system composed of a pump, reservoir, and oxygenator. Perfusate was plasma-based with a hemoglobin concentration of 4 to 6 g/dL.
  
  
  RESULTS
  Average warm ischemia time was 76 minutes. Perfusion was maintained at an average systolic pressure of 93 ± 2 mm Hg, flow 310 ± 20 mL/min, and vascular resistance 153 ± 16 mm Hg/L per minute. Average oxygen consumption was 1.1 ± 0.2 mL/kg per minute. Neuromuscular electrical stimulation continually displayed contraction until the end of perfusion, and histology showed no myocyte injury.
  
  
  CONCLUSIONS
  Human limb allografts appeared viable after 24 hours of near-normothermic ex situ perfusion. Although these results are early and need validation with transplantation, this technology has promise for extending allograft storage times.
authors.affiliation: 1 Department of Surgery, The University of Michigan Health System, Ann Arbor, MI.2 Department of Orthopedic Surgery, The University of Michigan Health System, Ann Arbor, MI.3 Gift of Life of Michigan, Ann Arbor, MI.4 Lung Bioengineering United Therapeutics Corporation, Silver Spring, MD.5 Section of Transplant Surgery, Department of Surgery, The University of Michigan Health System, Ann Arbor, MI.
authors.forename: Nicole L
authors.initials: NL
authors.lastname: Werner
authors.forename: Fares
authors.initials: F
authors.lastname: Alghanem
authors.forename: Stephanie L
authors.initials: SL
authors.lastname: Rakestraw
authors.forename: Dylan C
authors.initials: DC
authors.lastname: Sarver
authors.forename: Bruce
authors.initials: B
authors.lastname: Nicely
authors.forename: Richard E
authors.initials: RE
authors.lastname: Pietroski
authors.forename: Paul
authors.initials: P
authors.lastname: Lange
authors.forename: Steven M
authors.initials: SM
authors.lastname: Rudich
authors.forename: Christopher L
authors.initials: CL
authors.lastname: Mendias
authors.forename: Alvaro
authors.initials: A
authors.lastname: Rojas-Pena
authors.forename: John C
authors.initials: JC
authors.lastname: Magee
authors.forename: Robert H
authors.initials: RH
authors.lastname: Bartlett
authors.forename: Kagan
authors.initials: K
authors.lastname: Ozer
mesh_terms: D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D001926:Brain Death; D064595:Composite Tissue Allografts / Q000098:blood supply* / Q000294:innervation / Q000637:transplantation*; D004558:Electric Stimulation; D004867:Equipment Design; D005260:Female; D006439:Hemodynamics; D006801:Humans; D008297:Male; D008875:Middle Aged; D009119:Muscle Contraction; D009926:Organ Preservation / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D010101:Oxygen Consumption; D010477:Perfusion / Q000009:adverse effects / Q000295:instrumentation / Q000379:methods*; D015427:Reperfusion Injury / Q000209:etiology / Q000517:prevention & control; D013997:Time Factors; D014019:Tissue Donors; D014022:Tissue Survival; D034941:Upper Extremity / Q000098:blood supply* / Q000294:innervation / Q000601:surgery*; D063986:Vascularized Composite Allotransplantation / Q000009:adverse effects / Q000379:methods*; D052096:Warm Ischemia
chemical_list: D015415:Biomarkers