Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and prese...Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and preservation of the heart,especially when a long cold ischemic time is required.Here,we propose a novel donor heart procurement and preservation method—crystalloid cardioplegia(CC)+UW involving an initial cardioplegic flush with crystalloid cardioplegia followed by preservation in UW solution.Our results demonstrated that compared with using UW solution alone,the CC+UW method could effectively reduce metabolite consumption and suppress the activation of the NFκB signaling pathway in a pig model.NR4A3 was found to be upregulated in CC+UW,which could suppress the expression of DUSP2and thereby decrease p65 phosphorylation.In addition,the CC+UW method increased intraventricular pressure and improved electrical conduction and rhythm in Langendorff-perfused rat hearts.Mediumterm survival data for heart transplant patients also confirmed the benefits of this method.In conclusion,our study identifies the CC+UW method as an effective strategy for donor heart procurement and preservation,showing that it can reduce energy consumption and decrease inflammation;therefore,this method is a promising technique for expanding the criteria for heart transplantation and alleviating the shortage of donor hearts.展开更多
基金supported by the National Key Research and Development Program(2021YFA1101900)Key Research Development Program of Hubei Province(2020BCA061)+1 种基金the National Natural Science Foundation of China(82200410,82470423,82204659,and 82300413)Hubei Provincial Natural Science Foundation Projects(JCZRYB202500142)。
文摘Static cold storage(SCS)remains the gold standard for preserving donor hearts for heart transplantation.The currently used University of Wisconsin(UW)solution has limitations in inducing rapid cardiac arrest and preservation of the heart,especially when a long cold ischemic time is required.Here,we propose a novel donor heart procurement and preservation method—crystalloid cardioplegia(CC)+UW involving an initial cardioplegic flush with crystalloid cardioplegia followed by preservation in UW solution.Our results demonstrated that compared with using UW solution alone,the CC+UW method could effectively reduce metabolite consumption and suppress the activation of the NFκB signaling pathway in a pig model.NR4A3 was found to be upregulated in CC+UW,which could suppress the expression of DUSP2and thereby decrease p65 phosphorylation.In addition,the CC+UW method increased intraventricular pressure and improved electrical conduction and rhythm in Langendorff-perfused rat hearts.Mediumterm survival data for heart transplant patients also confirmed the benefits of this method.In conclusion,our study identifies the CC+UW method as an effective strategy for donor heart procurement and preservation,showing that it can reduce energy consumption and decrease inflammation;therefore,this method is a promising technique for expanding the criteria for heart transplantation and alleviating the shortage of donor hearts.
