Reperfusion injury to steatotic rat livers after transplantation can be attenuated with a modified HTK solution

Aims: Ischemia/reperfusion injury (IRI) is still an obstacle especially in fatty livers. Most recently a modified histidine-tryptophan-ketoglutarate (HTK) solution, Custodiol-N, has been developed. This solution contains N-acetyl-histidine as buffer, the amino acids aspartate, glycine, alanine, and arginine to limit ischemic injury and to improve reperfusion and the iron chelators deferoxamine and LK 614 to inhibit cold-induced cell injury. This study was designed to test the effects of Custodiol-N on IRI to fatty livers in a rat liver transplantation model.

Methods: Moderate steatosis was induced by a single dose of ethanol (8g/kg BW) to female Sprague-Dawley (SD) donor rats 20h before organ harvest. Livers were harvested and cold stored at 4°C for 8 hours with either HTK solution or Custodiol-N before transplantation. Serum transaminases and histology were compared at 1h, 8h and 24h after reperfusion (n=8 animals per group). Survival was compared after 7 days.

Results: Custodiol-N significantly improved permanent survival from 12.5% in controls to 87.5% after 7 days. Further, Custodiol-N decreased the release of AST, ALT and LDH to up to 25% (e.g. AST after 24h 14456±11493 vs. 4584±2340) of controls (p<0.05). These results were confirmed by histology.

Conclusions: These results clearly demonstrate that Custodiol-N is superior to the traditional HTK solution in experimental fatty liver transplantation.

cold storage - livertransplantation - preservation - steatosis