gms | German Medical Science

Background: 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.

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.

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.

Figure 1 [Fig. 1]

Conclusion: HR effectively enhances survival of marginally preserved liver grafts in the large animal and warrants a clinical proof-of-concept study.