Journal
AMERICAN JOURNAL OF TRANSPLANTATION
Volume 19, Issue 11, Pages 3139-3148Publisher
WILEY
DOI: 10.1111/ajt.15539
Keywords
animal models; murine; basic (laboratory) research; science; heart transplantation; cardiology; ischemia-reperfusion injury (IRI); molecular biology; organ perfusion and preservation; translational research; science
Categories
Funding
- MRC [MC_PC_15047, MR/S002626/1] Funding Source: UKRI
- China Scholarship Council [201706170200] Funding Source: Medline
- CIHR Funding Source: Medline
- Medical Research Council [MC_PC_15047, MR/S002626/1] Funding Source: Medline
- Natural Sciences and Engineering Research Council of Canada Funding Source: Medline
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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 ischemia time is adversely associated with primary graft function and long-term survival. 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/reoxygenation 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 quantitative ultrasound scan, against prolonged cold ischemia-reperfusion injury (24 hours at 4 degrees C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP39 protects cardiac grafts from prolonged ischemia, highlighting its therapeutic potential in preventing ischemia-reperfusion injury in heart transplant.
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