Hypothermic oxygenated machine perfusion in porcine donation after circulatory determination of death liver transplant.
BACKGROUND
Livers from donation after circulatory determination-of-death (DCD) donors suffer ischemic injury during a preextraction period of cardiac arrest and are infrequently used for transplantation; they have the potential, however, to considerably expand the donor pool. We aimed to determine whether hypothermic oxygenated machine perfusion would improve or further deteriorate the quality of these livers using a clinically relevant porcine model.


METHODS
Donor livers were subjected to 90 min of cardiac arrest and preserved at 4°C with either static cold storage using University of Wisconsin solution (CS, n=6) or oxygenated machine perfusion using University of Wisconsin machine perfusion solution and 25% physiological perfusion pressures (HMP, n=5). After 4 hr of preservation, livers were transplanted into recipient pigs, which were followed intensively for up to 5 days.


RESULTS
Five-day survival was 0 in CS and 20% in HMP. Immediately after reperfusion, hepatocellular injury and function were improved in HMP versus CS. However, HMP grafts also demonstrated significant endothelial and Kupffer cell injury, and a progressive lesion developed 24 to 48 hr after reperfusion that led to death in all but one of the recipient animals.


CONCLUSIONS
Although hypothermic oxygenated machine perfusion performed using subphysiological perfusion pressures seems to offer some advantages over cold storage in the preservation of ischemically damaged livers, it simultaneously conditions endothelial and Kupffer cell injury that may ultimately lead to the failure of these grafts.
Liver Transplant Unit, Institut de Malaties Digestives, Hospital Clinic, CIBERehd, IDIBAPS, University of Barcelona, C/Villaroel 170, Barcelona, Spain. cfonde@clinic.ub.es
Constantino
C
Fondevila
Amelia J
AJ
Hessheimer
Mark-Hugo J
MH
Maathuis
Javier
J
Muñoz
Pilar
P
Taurá
David
D
Calatayud
Henri
H
Leuvenink
Antoni
A
Rimola
Juan C
JC
García-Valdecasas
Rutger J
RJ
Ploeg
D000241:Adenosine / Q000494:pharmacology; D000493:Allopurinol / Q000494:pharmacology; D000818:Animals; D042783:Endothelial Cells / Q000502:physiology; D005978:Glutathione / Q000494:pharmacology; D006324:Heart Arrest, Induced; D007328:Insulin / Q000494:pharmacology; D015850:Interleukin-6 / Q000235:genetics; D016031:Liver Transplantation / Q000379:methods* / Q000401:mortality; D008297:Male; D009926:Organ Preservation / Q000379:methods*; D019188:Organ Preservation Solutions / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D011887:Raffinose / Q000494:pharmacology; D013552:Swine; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics
D007328:Insulin; D015850:Interleukin-6; D019188:Organ Preservation Solutions; D012333:RNA, Messenger; D014409:Tumor Necrosis Factor-alpha; C055206:University of Wisconsin-lactobionate solution; D000493:Allopurinol; D005978:Glutathione; D000241:Adenosine; D011887:Raffinose