Comprehensive Review on Custodiol-N (HTK-N) and its Molecular Side of Action for Organ Preservation
| Autor: | Peter Schemmer, Judith Kahn |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
Iron Inflammatory response Organ Preservation Solutions Ischemia Pharmaceutical Science Custodiol-N Pharmacology Mitochondrial Membrane Transport Proteins Potassium Chloride Microcirculation 03 medical and health sciences In vivo Animals Humans Medicine Mannitol Cryopreservation Mitochondrial Permeability Transition Pore business.industry Organ Preservation medicine.disease Organ Retrieval Transplantation Glucose 030104 developmental biology Reperfusion Injury Reactive Oxygen Species business Reperfusion injury Procaine Biotechnology |
| Zdroj: | Current Pharmaceutical Biotechnology. 18:1237-1248 |
| ISSN: | 1389-2010 |
| Popis: | Background The later fate of a graft is highly dependent on its initial quality. Aside from that the three predominant phases during transplantation (Tx) organ retrieval, cold static preservation and reperfusion cause in a direct and indirect manner graft injury. There is complex ischemia reperfusion injury (IRI) triggered during the whole process of Tx which contributes to further damage of the graft. Methods The today's organ preservation with commercially available solutions that all have toxic potential per se is still imperfect. Thus, improved preservation solutions are desperately needed to be able to even safely preserve grafts from extended criteria donors which are more susceptible to especially IRI. Most recently, a modified less toxic histidine-tryptophan-ketoglutarate (HTK; Custodiol®) the so called histidine-tryptophan-ketoglutarate-N (HTK-N) for both better cardioplegia and organ preservation for Tx has been developed. It is characterized as an electrolyte balanced, iron chelatorsupplemented, and amino acid-fortified organ preservation solution with replaced buffer ameliorating resistance to injury during the cold static preservation with subsequent IRI. Numerous in vitro and in vivo experiments have shown the superiority of the HTK-N solution in ROS generation, microcirculation, and subsequent inflammatory response compared with HTK. Results According to data available to date, HTK-N has both lower cytotoxicity and higher protective potential than HTK. First clinical studies on both HTK-N for cardioplegia in cardiac surgery and for organ preservation for transplantation have been performed or are ongoing. Conclusion In this review, the novelty and composition of HTK-N and studies investigating the potential of this new solution are focussed, after summarizing the most relevant molecular mechanisms of IRI. |
| Databáze: | OpenAIRE |
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