Technique for prolonged normothermic ex vivo lung perfusion.
BACKGROUND
The inhibition of cellular metabolism induced by hypothermia obviates the possibility of substantial reparative processes occurring during organ preservation. The aim of this study was to develop a technique of extended (12-hour) ex vivo lung perfusion (EVLP) at normothermia for assessment and protective maintenance of the donor lung.


METHODS
Six double-lung blocks from 35-kg pigs and 5 single human lungs were subjected to 12 hours of normothermic EVLP using acellular Steen Solution. In the animal studies, the left lung was transplanted into recipients at the end of EVLP and reperfused for 4 hours to evaluate the impact of prolonged EVLP on post-transplant lung function. A protective mode of mechanical ventilation with controlled perfusion flows and pressures in the pulmonary vasculature were employed during EVLP. Lung oxygenation capacity (DeltaPo(2)), pulmonary vascular resistance and airway pressures were evaluated in the system. Red blood cells were added to the perfusate to a hematocrit of 20% at the end of human lung EVLP to study lung functional assessment with and without cells.


RESULTS
Lung function was stable during 12 hours of EVLP. This stability during prolonged normothermic EVLP translated into excellent post-transplant lung function (Pao(2)/Fio(2): 527 +/- 22 mm Hg), low edema formation (wet/dry ratio: 5.24 +/- 0.38) and preserved lung histology after transplantation. The acellular perfusion assessment of lung function accurately correlated with post-transplant graft function.


CONCLUSIONS
Twelve hours of EVLP at physiologic temperatures using an acellular perfusate is achievable and maintains the donor lungs without inflicting significant added injury. This system can be used to assess, maintain and treat injured donor lungs.
Cypel
Marcelo
M
Latner Thoracic Surgery Research Laboratories, Toronto General Hospital Research Institute, Toronto Lung Transplant Program, University Health Network, University of Toronto, Toronto, Ontario, Canada.
Yeung
Jonathan C
JC
Hirayama
Shin
S
Rubacha
Matthew
M
Fischer
Stefan
S
Anraku
Masaki
M
Sato
Masaaki
M
Harwood
Stephen
S
Pierre
Andrew
A
Waddell
Thomas K
TK
de Perrot
Marc
M
Liu
Mingyao
M
Keshavjee
Shaf
S
D000818:Animals; D005112:Extracorporeal Circulation / Q000295:instrumentation / Q000379:methods; D007035:Hypothermia / Q000517:prevention & control; D008168:Lung / Q000502:physiology*; D016040:Lung Transplantation / Q000379:methods* / Q000502:physiology*; D008297:Male; D023421:Models, Animal; D009926:Organ Preservation / Q000379:methods; D010477:Perfusion / Q000379:methods*; D015424:Reperfusion / Q000379:methods; D012129:Respiratory Function Tests; D013552:Swine; D013997:Time Factors; D014019:Tissue Donors