Hypothermic perfusion protocol development for donor heart preservation

Hypothermic perfusion has been introduced for donor heart storage for ∼9 hours. However, opportunities exist to further define the optimal physiological conditions for a more prolonged period with 18 hours of preservation. In particular, the utility of exogenous cellular therapies such as administration of mitochondria are unknown in this setting.

We examined several key aspects of the protocol for hypothermic perfusion of the donor heart. Yorkshire pigs hearts were used for perfusion with histidine-tryptophan-ketoglutarate (HTK) solution at ∼8 °C for 18 hours under different conditions followed by reanimation with normothermic perfusion for 3 hours.

HTK perfusate oxygenation was associated with worse contractility (Max dP/dt 630.38 ± 376.63 mm Hg/s vs 1101.80 ± 338.93 mm Hg/s, P = .028) and relaxation (Min dP/dt -512.31 ± 275.23 mm Hg/s vs -1009.26 ± 443.31 mm Hg/s, P = .028) as well as increased cell death and lower coronary blood flow. Compared with fresh HTK perfusion, recirculation of the perfusate was associated with worse contractility (Max dP/dt 671.60 ± 249.00 mm Hg/s vs 987.18 ± 219.16 mm Hg/s, P = .021) and relaxation (Min dP/dt -477.83 ± 158.02 mm Hg/s vs -824.48 ± 270.93 mm Hg/s, P = .003), which was accompanied by greater cell death. Antegrade coronary perfusion was better than retrograde via coronary sinus, resulting in superior contractility (Max dP/dt 987.18 ± 219.16 mm Hg/s vs 612.67 ± 258.40 mm Hg/s, P = .005) and relaxation (Min dP/dt -824.48 ± 270.93 mm Hg/s vs -401.59 ± 143.59 mm Hg/s, P = .001) as well as less cell death. The administration of porcine mitochondria promptly improved contractility (Max dP/dt 1764.06 ± 542.34 mm Hg/s vs 1101.80 ± 338.93 mm Hg, P = .007).

Avoidance of excess oxygenation, use of fresh HTK, antegrade cardioplegia delivery, as well as delivery of stored frozen mitochondria are key for the success of greatly prolonged hypothermic cardiac perfusion preservation.