Gene Expression in Ex Vivo Perfused Porcine Hearts: Identification of a Molecular Injury-Repair Response

Purpose Cardiac transplantation is a life-saving intervention for advanced heart failure but it is limited by a shortage of suitable donor organs. Ex vivo heart perfusion (EVHP) represents a promising alternative for organ preservation and repair. We aimed to assess the utility of gene expression for better understanding and monitoring cardiac injury and repair during EVHP. Methods Biopsies were obtained from 46 porcine hearts either in vivo (IV, n=7) or after 12 hours of ex vivo heart (EVHP, n=32) or combined heart-liver (H+L, n=7) perfusion. Functional parameters were recorded during EVHP. Histology was assessed for features of cardiac injury. NanoString was used to measure 68 previously-described genes related to cardiac injury and repair. Molecular data were assessed for differential expression and correlated with function and histology. Results Principal component analysis demonstrated distinct clustering of sample groups based on gene expression patterns (Figure 1). 44 genes were significantly upregulated and 12 genes were significantly downregulated in EVHP vs. IV (FDR Conclusion These data suggest that EVHP induces a molecular injury response that correlates with function. Interestingly, molecular injury appears reduced in combined heart-liver perfusion. This represents a novel approach for assessing mechanism and extent of organ injury during EVHP.