Initial cardioplegic flush with crystalloid cardioplegia improves donor heart preservation and function via NR4A3 upregulation and metabolic reprogramming.

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 DUSP2 and thereby decrease p65 phosphorylation. In addition, the CC+UW method increased intraventricular pressure and improved electrical conduction and rhythm in Langendorff-perfused rat hearts. Medium-term 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.