Liver integrity after warm ischemia in situ and brief preservation ex vivo: the value of aerobic post-conditioning.
We evaluated the respective effects of warm ischemic injury in non-heart-beating donor (NHBD) grafts and/or cold ischemia time on liver viability. Eventually, the restorative potential of oxygenated hypothermic perfusion after cold storage should be investigated. Livers were retrieved from male Wistar rats and preserved with HTK-solution for 6h or 18 h by cold storage (CS). Organ retrieval took place either prior to (ctrl.) or 30 min after cardiac arrest (NHBD). Compared to 6h CS of ctrl. livers, enzyme leakage and functional recovery (oxygen consumption, ammonia clearance, bile production) upon warm reperfusion were massively deteriorated after 18 h CS in NHBD-livers. By contrast, 6h CS of NHBD resulted in an only limited impairment of all parameters, which was found quite similar to the results in ctrl. after 18 h CS. Induction of cellular apoptosis (cleavage PARP) was found equally influenced by preceding warm ischemia (NHBD) or extended times of CS, but significantly triggered only by the combination of both events. After 6h of CS, 1h of oxygenated hypothermic machine perfusion ('post-conditioning') was able to bring the performance of NHBD-liver into line with the controls. Based on this work, we concluded that a limited time of warm ischemia in the donor only multiplied graft injury after long-term CS, but does not need to preclude acceptable results if reperfusion is initiated after short periods of CS. Moreover, conditioning of those grafts is effective even 1h prior to implantation and may help to judge liver viability according to adequate parameters after hypothermic machine perfusion has been established.
Manekeller
Steffen
S
Surgical Research Division, University Clinic of Surgery, Sigmund Freud Str. 25, 53127 Bonn, Germany.
Dobberahn
Viola
V
Hirner
Andreas
A
Minor
Thomas
T
D000332:Aerobiosis; D000410:Alanine Transaminase / Q000378:metabolism; D017209:Apoptosis; D053453:Caspase 9 / Q000378:metabolism; D003080:Cold Temperature; D024161:Collagen Type XI / Q000378:metabolism; D006323:Heart Arrest; D006801:Humans; D008099:Liver / Q000378:metabolism; D016031:Liver Transplantation; D009926:Organ Preservation / Q000379:methods*; D052096:Warm Ischemia
C499319:COL11A2 protein, human; D024161:Collagen Type XI; D000410:Alanine Transaminase; D053453:Caspase 9