Songjie Cai1, Naotsugu Ichimaru, Mingyi Zhao, Masayuki Fujino, Hidenori Ito, Urara Ota, Motowo Nakajima, Tohru Tanaka, Norio Nonomura, Xiao-Kang Li, Shiro Takahara. 1. 1 Division of Transplantation Immunology, National Research Institute for Child Health and Development, Tokyo, Japan. 2 Department of Advanced Technology for Transplantation, Osaka University Graduate School of Medicine, Osaka, Japan. 3 AIDS Research Center, National Institute of Infectious Diseases, Tokyo, Japan. 4 SBI Pharmaceuticals Co., Ltd., Tokyo, Japan. 5 Department of Urology, Osaka University Graduate School of Medicine, Osaka, Japan.
Abstract
BACKGROUND: One of the major events in ischemia-reperfusion (I/R)-induced heart injury in cardiac transplantation is the generation of reactive oxygen species. We hypothesized that a novel preservation solution called SBI-SEIIKU II (SS-II) contains 3 antioxidant reagents: L-cysteine, glycine, ascorbic acid/ascorbic acid-2-phosphate magnesium, which can block the generation of reactive oxygen species to result in a prolongation of the cold storage time via attenuating I/R injury. METHODS: C57BL/6CrSlc(B6) mice underwent syngeneic mice heterotopic heart transplantation, and the animals were derived into 3 groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in histidine-tryptophan-ketoglutarate (HTK) for 24 and 48 hours (HTK group), and recipients with grafts preserved in SS-II for 24 and 48 hours (SS-II group). RESULTS: After 48 hours of preservation, there were no grafts that survived in the HTK group; however, the SS-II group had a high survival rate. After 24 hours of preservation, SS-II decreased the oxidative damage, myocardial apoptosis, and the infiltration of macrophages and neutrophils in the cardiac grafts in the early phase and suppressed the development of myocardial fibrosis in long-term grafts compared with HTK. CONCLUSIONS: The SS-II prolongs the acceptable cold storage time and protects the myocardium from I/R injury via inhibiting oxidative stress-associated damage. We believe that this novel preservation solution may be simple and safe for use in the clinical transplantation field.
BACKGROUND: One of the major events in ischemia-reperfusion (I/R)-induced heart injury in cardiac transplantation is the generation of reactive oxygen species. We hypothesized that a novel preservation solution called SBI-SEIIKU II (SS-II) contains 3 antioxidant reagents: L-cysteine, glycine, ascorbic acid/ascorbic acid-2-phosphatemagnesium, which can block the generation of reactive oxygen species to result in a prolongation of the cold storage time via attenuating I/R injury. METHODS: C57BL/6CrSlc(B6) mice underwent syngeneic mice heterotopic heart transplantation, and the animals were derived into 3 groups: recipients with nonpreserved grafts (control group), recipients with grafts preserved in histidine-tryptophan-ketoglutarate (HTK) for 24 and 48 hours (HTK group), and recipients with grafts preserved in SS-II for 24 and 48 hours (SS-II group). RESULTS: After 48 hours of preservation, there were no grafts that survived in the HTK group; however, the SS-II group had a high survival rate. After 24 hours of preservation, SS-II decreased the oxidative damage, myocardial apoptosis, and the infiltration of macrophages and neutrophils in the cardiac grafts in the early phase and suppressed the development of myocardial fibrosis in long-term grafts compared with HTK. CONCLUSIONS: The SS-II prolongs the acceptable cold storage time and protects the myocardium from I/R injury via inhibiting oxidative stress-associated damage. We believe that this novel preservation solution may be simple and safe for use in the clinical transplantation field.
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Authors: Songjie Cai; John Y Choi; Thiago J Borges; Hengcheng Zhang; Ji Miao; Takaharu Ichimura; Xiaofei Li; Simiao Xu; Philip Chu; Siawosh K Eskandari; Hazim Allos; Juliano B Alhaddad; Saif A Muhsin; Karim Yatim; Leonardo V Riella; Peter T Sage; Anil K Chandraker; Jamil R Azzi Journal: Sci Rep Date: 2020-08-28 Impact factor: 4.379