Artikel
Hypothermic reconditioning by gaseous oxygen improves survival after transplantation of marginally preserved livers in the pig
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Veröffentlicht: | 20. Mai 2011 |
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Introduction: The quality of cold-stored livers slowly declines beyond approximately 8 hours of ischemia and the risk of primary dys- or non-function increases. Here provide in vivo evidence for the efficacy of the previously proposed end-ischemic gaseous oxygen persufflation to resuscitate large size liver grafts, unexpectedly subjected to long storage times.
Materials and methods: Porcine livers (n=10) were harvested according to standard multi-organ procurement protocol and subjected to species specific extended cold storage (CS) at 4°C. Hypothermic reconditioning(HR) was performed in some livers by insufflation of gaseous oxygen via the caval vein for 2 hours prior to transplantation. Viability was assessed by orthotopic liver transplantation and one week follow-up.
Results: HR significantly improved initial graft function 1h after transplantation with an approx. 30% reduction of enzyme leakage (AST, LDH), massive lowering of blood ammonia levels and notably better coagulation (prothrombin-time improved by the factor 2, p<0.05). Mean recipient survival after CS was 28+/-22 hours, while one week survival was 100% in the HR group. At that time coagulation parameters were in the normal range and histological analysis disclosed healthy liver tissue with normal trabecular architecture in the treated grafts (Figure 1 [Fig. 1]). Preliminary molecular analyses could identify the prevention of ischemia induced decline of cellular autophagy-cleavage of LC3II, activation of AMPK salvage pathway and mitochondrial energy homeostasis (ATP) as operative mechanisms among the protective effects provided by HR.
Conclusion: HR effectively enhances survival of marginally preserved liver grafts in the large animal and warrants a clinical proof-of-concept study.