Enhanced preservation of pig cardiac allografts by combining erythropoietin with glyceryl trinitrate and zoniporide

Erythropoietin has a tissue-protective effect independent of its erythropoietic effect that may be enhanced by combining it with the nitric oxide donor glyceryl trinitrate (GTN) and the sodium-hydrogen exchange inhibitor zoniporide in rat Hearts stored with an extracellular-based preservation solution (EBPS). We thus sought to test this combination of agents in a porcine model of orthotopic heart transplantation incorporating donor brain death and total ischaemic time of approximately 260 min. Pig Hearts were stored in one of four storage solutions: unmodified EBPS (CON), EBPS supplemented with GTN and zoniporide (GZ), EBPS supplemented with erythropoietin and zoniporide (EZ), or EBPS supplemented with all three agents (EGZ). A total of 4/5 EGZ Hearts were successfully weaned from cardiopulmonary bypass compared with only 2/5 GZ Hearts, 0/5 CON Hearts and 0/5 EG Hearts (p = 0.017). Following weaning from bypass EGZ Hearts demonstrated superior contractility and haemodynamics than GZ Hearts. All weaned Hearts displayed impaired diastolic function. Release of troponin I from EGZ Hearts was lower than all other groups. In conclusion, supplementation of EBPS with erythropoietin, glyceryl trinitrate and zoniporide provided superior donor heart preservation than all other strategies tested.