Energy charge restoration, mitochondrial protection and reversal of preservation induced liver injury by hypothermic oxygenation prior to reperfusion.
We investigated the benefit of two different techniques for resuscitating marginally preserved liver grafts, unexpectedly subjected to long storage times. Rat livers were cold-stored for 22h (CS22). Some grafts were subsequently subjected to 90min of hypothermic reconditioning by venous systemic oxygen persufflation (VSOP) or oxygenated hypothermic machine perfusion (HMP). Livers stored for only 6h (CS6) served as reference. Viability of the livers was assessed thereafter by warm reperfusion in vitro. VSOP and HMP significantly increased endischemic tissue energy charge, and abrogated cellular enzyme loss upon reperfusion even significantly below control values. Ammonia clearance and bile production were more than 3-fold improved to similar values as CS6. Hypothermic reconditioning by both techniques induced mitochondrial chaperone expression (HSP70 family) and significantly improved early resumption of oxygen utilisation upon reperfusion. Viability of long preserved liver grafts can be augmented by transient hypothermic reconditioning using either machine perfusion or gaseous oxygen persufflation, both preventing initial mitochondrial dysfunction and subsequent tissue injury.