Supplementing preservation solution with mitochondria‐targeted H 2 S donor AP 39 protects cardiac grafts from prolonged cold ischemia–reperfusion injury in heart transplantation

Heart transplant has been accepted as the standard treatment for end‐stage heart failure. Because of its susceptibility to ischemia–reperfusion injury, the heart can be preserved for only 4 to 6 hours in cold static preservation solutions. Prolonged is‐ chemia time is adversely associated with primary graft function and long‐term sur‐ vival. New strategies to preserve donor hearts are urgently needed. We demonstrate that AP39, a mitochondria‐targeting hydrogen sulfide donor, significantly increases cardiomyocyte viability and reduces cell apoptosis/death after cold hypoxia/reoxy‐ genation in vitro. It also decreases gene expression of proinflammatory cytokines and preserves mitochondria function. Using an in vivo murine heart transplant model, we show that preserving donor hearts with AP39‐supplemented University of Wisconsin solution (n = 7) significantly protects heart graft function, measured by quantita‐ tive ultrasound scan, against prolonged cold ischemia–reperfusion injury (24 hours at 4°C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP39 protects cardiac grafts from pro‐ longed ischemia, highlighting its therapeutic potential in preventing ischemia–reper‐ fusion injury in heart transplant.