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Supplementing preservation solution with mitochondria‐targeted H 2 S donor AP 39 protects cardiac grafts from prolonged cold ischemia–reperfusion injury in heart transplantation
Author(s) -
Zhu Cuilin,
Su Yale,
Juriasingani Smriti,
Zheng Hao,
Veramkovich Vitali,
Jiang Jifu,
Sener Alp,
Whiteman Matthew,
Lacefield James,
Nagpal Dave,
Alotaibi Faizah,
Liu Kexiang,
Zheng Xiufen
Publication year - 2019
Publication title -
american journal of transplantation
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.89
H-Index - 188
eISSN - 1600-6143
pISSN - 1600-6135
DOI - 10.1111/ajt.15539
Subject(s) - medicine , reperfusion injury , ischemia , cold storage , heart transplantation , transplantation , cardiac function curve , proinflammatory cytokine , hypoxia (environmental) , mitochondrion , fibrosis , pharmacology , heart failure , cardiology , surgery , inflammation , biochemistry , biology , chemistry , organic chemistry , oxygen , horticulture
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 AP 39, 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 AP 39‐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°C), along with reducing tissue injury and fibrosis. Our study demonstrates that supplementing preservation solution with AP 39 protects cardiac grafts from prolonged ischemia, highlighting its therapeutic potential in preventing ischemia–reperfusion injury in heart transplant.