Cardiac Mitochondrial and Electrophysiological Changes in Transplanted Ovine Hearts Following Preservation by Hypothermic Oxygenated Perfusion

BACKGROUND: During heart transplantation (HTx), donor hearts are exposed to injury via brain death (BD) and cardiac preservation using static cold storage (SCS). Preservation using hypothermic oxygenated machine perfusion (HOPE) may reduce myocardial injury compared with SCS preservation. This study sought to better understand how the BD donor cardiac allograft is modified before HTx and posttransplant following HOPE preservation. METHODS: Using an ovine model, changes in mitochondrial respiratory function, cardiac contractility, and electrophysiology (biventricular endocardial signal amplitude, velocity, and Purkinje potential prevalence) were examined in brain dead (or Sham, nonneurological injury) sheep donor hearts at 2 stages of the HTx process. In the non-HTx group, donor hearts were assessed following 24 h of observation. In the HTx group, hearts were preserved using either SCS (2 h) or HOPE (2 or 8 h), orthotopically transplanted into a recipient sheep, and monitored for up to 6 h before assessment. RESULTS: BD impaired mitochondrial function and contractility and increased the extent of endocardial low voltage electrograms retrieved before preservation (non-HTx group). Following HTx, HOPE (both 2 and 8 h) improved cardiac mitochondrial function, contractility, Purkinje cell preservation, and conduction velocity compared with SCS. CONCLUSIONS: This study provides unique insight into the metabolic and electrophysiological derangements that the donor heart endures during transplantation. Furthermore, HOPE appears to overcome many of these challenges to both limit cardiac allograft injury and safely extend preservation time.