Evaluating the mechanism of action behind controlled hypothermic preservation of donor hearts: A randomized pilot study

Background: Controlled hypothermic preservation of donor hearts is associated with decreased post-transplant primary graft dysfunction compared to conventional cold storage. However, mechanisms underlying this benefit in human subjects are unclear. Methods: We randomized 20 heart transplant recipients at a single institution to receive donor hearts preserved with either controlled hypothermic preservation or standard cold storage. Right ventricular biopsies were obtained at donor heart recovery, immediately before implantation, and 7 days after transplantation. Protein expression profiles at each time point were evaluated using mass spectrometry, Protein Interaction Network Extractor analysis, and Ingenuity Pathway Analysis. Results: Immediately before implantation, controlled hypothermic preservation was associated with increased protein expression related to fatty acid metabolism, mitochondrial intermembrane space, and contractile fiber machinery. Pathway analysis indicated increased cell viability, autophagy, and upregulation of AMP-activated protein kinase pathway with controlled hypothermic preservation. By post-transplant day 7, the protein expression profiles of the 2 groups were similar. However, controlled hypothermic preservation was associated with increased expression in the peroxisome proliferator-activated receptor signaling pathway and fatty acid oxidation. Conclusions: Controlled hypothermic preservation of donor hearts shows beneficial time-dependent variability in protein expression that may confer improved organ quality at the time of transplantation.