Objective: Ex-vivo machine perfusion (EVMP) of donor hearts with normothermic blood is a new method for donor heart maintenance. Nevertheless, it was shown that EVMP with hypothermic, crystalloid histidine-tryptophane-ketoglutarate (HTK) solution is superior to blood perfusion to maintain left-ventricular (LV) contractility of donor hearts in a porcine model. However, transcriptomic changes of EVMP of donor hearts with HTK compared to blood have not been investigated yet.

Methods: In a pig model, hearts were maintained for 4 h by EVMP with normothermic, oxygenated blood of the donor animal (BP group, N=8) or hypothermic oxygenated HTK solution (HTK, N=8), followed by reperfusion with fresh blood for 2 h. In a Control group (N=7), hearts were not maintained for 4 h. We performed transcriptomics from LV myocardial samples using microarrays (25,470 genes).

Results: In BP, 145 genes were up-, and 129 genes were downregulated; and in HTK, 93 genes were up-, and 306 genes were downregulated, both compared to Control. In DCD-HTK compared to DCD-BP, 156 genes were upregulated, involved in intracellular oxygen transport, heat shock factor expression, and glycosamino glycan metabolism, and 710 genes were downregulated, involved in apoptosis,  interleukine signaling, and chemokine binding.

Conclusions: EVMP with hypothermic, oxygenated HTK modifies the transcriptome of hearts and leads to an activation of a large variety of potentially protective pathways and downregulation of potentially detrimental pathways in the myocardium of hearts.