HTK-N: Modified Histidine-Tryptophan-Ketoglutarate Solution-A Promising New Tool in Solid Organ Preservation.

To ameliorate ischemia-induced graft injury, optimal organ preservation remains a critical hallmark event in solid organ transplantation. Although numerous preservation solutions are in use, they still have functional limitations. Here, we present a concise review of a modified Histidine-Tryptophan-Ketoglutarate (HTK) solution, named HTK-N. Its composition differs from standard HTK solution, carrying larger antioxidative capacity and providing inherent toxicity as well as improved tolerance to cold aiming to attenuate cold storage injury in organ transplantation. The amino acids glycine, alanine and arginine were supplemented, N-acetyl-histidine partially replaced histidine, and aspartate and lactobionate substituted chloride. Several in vitro studies confirmed the superiority of HTK-N in comparison to HTK, being tested in vivo in animal models for liver, kidney, pancreas, small bowel, heart and lung transplantation to adjust ingredients for required conditions, as well as to determine its innocuousness, applicability and potential advantages. HTK-N solution has proven to be advantageous especially in the preservation of liver and heart grafts in vivo and in vitro. Thus, ongoing clinical trials and further studies in large animal models and consequently in humans are inevitable to show its ability minimizing ischemia-induced graft injury in the sequel of organ transplantation.

EPOR2/ßcR2-independendent effects of low-dose epoetin-α in porcine liver transplantation.

Ischemia-reperfusion injury (IRI) remains a key component of graft damage during transplantation. Erythropoietin (EPO) induces anti-inflammatory and anti-apoptotic effects via the EPOR2/ßcR2 complex, with a potential risk of thrombosis. Previous work indicates that EPO has EPOR2/ßcR2-independent protective effects via direct effects on the endothelium. As the EPOR2/ßcR2 receptor has a very low affinity for EPO, we aimed to test the hypothesis that EPO doses below the level that stimulate this receptor elicit cytoprotective effects via endothelial stimulation in a porcine liver transplantation model. Landrace pigs underwent allogenic liver transplantation (follow-up: 6 h) with a portojugular shunt. Animals were divided into two groups: donor and recipient treatment with low-dose EPO (65 IU/kg) or vehicle, administered 6 h before cold perfusion and 30 min after warm reperfusion. Fourteen of 17 animals (82.4%) fulfilled the inclusion criteria. No differences were noted in operative values between the groups including hemoglobin, cold or warm ischemic time. EPO-treated animals showed a significantly lower histopathology score, reduced apoptosis, oxidative stress, and most important a significant up-regulation of endothelial nitric oxide (NO) synthase (eNOS). Donor and recipient treatment with low-dose EPO reduces the hepatic IRI via EPOR2/ßcR2-independent cytoprotective mechanisms and represents a clinically applicable way to reduce IRI.