Supplementing preservation solution with mitochondria‐targeted H2S donor AP39 protects cardiac grafts from prolonged cold ischemia–reperfusion injury in heart transplantation. Issue 11 (3rd September 2019)

• Record Type: Journal Article
• Authors: 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
• Is Part Of: American journal of transplantation. Volume 19:Issue 11(2019)
• Page Start: 3139
• Page End: 3148
• Publication Date: 2019-09-03
• Subjects: animal models: murine -- basic (laboratory) research/science -- heart transplantation/cardiology -- ischemia–reperfusion injury (IRI) -- molecular biology -- organ perfusion and preservation -- translational research/science; Transplantation of organs, tissues, etc -- Periodicals; 617.95
• DOI: 10.1111/ajt.15539
• Languages: English
• ISSNs: 1600-6135

Abstract

Abstract : 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°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. Abstract : Preserving donor hearts with mitochondria‐targeted H S donor AP39–supplemented preservation solution prevents heart grafts from prolonged cold ischemia–reperfusion injury in heart transplantation by protecting mitochondrial integrity and reducing oxidative stress, cell apoptosis/death, and fibrosis.