Ex vivo hypothermic oxygenated perfusion allows extended heart preservation in a donation-after-circulatory-death porcine model

ObjectivesDonation after circulatory death (DCD) expands the donor heart pool but is limited by warm ischemia and short preservation times. Hypothermic oxygenated perfusion (HOPE) extends storage beyond the 4-6-hour limit of static cold storage (SCS), yet cellular and molecular responses remain undefined. We evaluate cardiomyocyte integrity and functional recovery of DCD porcine hearts after in situ reanimation with normothermic regional perfusion (NRP) and preservation by SCS (2h) or HOPE (24h) and assess the impact of NRP under DCD conditions. MethodsNine Yorkshire pigs underwent DCD cardiectomy. Six animals experienced 15 min warm ischemia followed by 60 min NRP. Three hearts were preserved for 2h with SCS and three for 24h with HOPE. A second DCD group (n=3) underwent direct procurement without NRP and 2h of HOPE preservation. All hearts were reanimated by normothermic machine perfusion to assess rhythm and contractility. Cardiomyocyte viability, transcriptomics, and metabolomics were analyzed. ResultsAfter DCD+NRP, 2h SCS preserved intact cardiomyocyte viability. HOPE maintained measurable, though reduced, viability at 24h, while 24h SCS failed even under donation after brain death (DBD) conditions. Transcriptomic and metabolomic analyses showed marginal differences between 2h SCS and 24h HOPE. All 24h HOPE hearts regained sinus rhythm but showed reduced contractility vs 2h SCS. Without NRP, 2h HOPE hearts showed the lowest viability and contractility. ConclusionsHOPE supports extended preservation of DCD hearts, but viability and function decline by 24h. NRP is essential for functional recovery of hearts preserved at hypothermic temperatures in a porcine preclinical DCD model. Graphical Abstract O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=186 SRC="FIGDIR/small/25337185v1_ufig1.gif" ALT="Figure 1"> View larger version (69K): org.highwire.dtl.DTLVardef@1639a35org.highwire.dtl.DTLVardef@210e49org.highwire.dtl.DTLVardef@30f455org.highwire.dtl.DTLVardef@1f904db_HPS_FORMAT_FIGEXP M_FIG C_FIG