Cold Ischemic Organ Preservation: Lessons from Natural Systems

Abstract

Mammalian hibernators offer natural models for investigating solutions to the metabolic injuries that accrue during cold ischemic storage of human organs removed for transplant. Knowledge of the biochemical mechanisms that regulate and stabilize metabolism to ensure long-term viability in the hypometabolic, hypothermic state of hibernation could lead to applied treatments that could increase the time that excised organs can be maintained in cold storage and/or improve recovery of function after implantation. New research has documented the widespread role of reversible protein phosphorylation control of metabolism in achieving the coordinated suppression of metabolic rate that greatly extends viability during torpor. Analysis of hibernation-induced gene expression is proving to be of crucial importance for identifying the genes and proteins that are up-regulated to address organ-specific concerns during torpor. In particular, the power of complementary deoxyribonucleic acid (cDNA) array screening is identifying families of proteins that are up-regulated during hibernation (eg, serpins, heat shock proteins, antioxidants, membrane transporters) and highlighting previously unrecognized areas of cellular metabolism as contributing to the hibernation phenotype. These offer new targets for innovative applied treatments that could enhance cyto-protection and cold ischemia survival of organ explants.