Ex Situ Heart Perfusion and Standard of Care Cold Storage Differentially Affect the Ischemic Secretome of Donor Hearts in Perfusates but Not the Reperfusion Response in Recipient Plasma

Abstract

Purpose Various allograft preservation procedures influence the donor organ status that may be reflected by the cytokine/chemokine microenvironment in heart transplant (HTx) recipients. In addition, the microenvironment in perfusion solutions may be informative in terms of organ function. Therefore, we aimed to compare the secretomes in recipient plasma and perfusates of two cohorts of HTx patients whose hearts were either preserved using ex situ heart perfusion (ESHP) or standard of care (SOC) cold static preservation in order to identify potential biomarker candidates for heart preservation. Methods Using multiplex techniques, we measured 50 cytokines/chemokines, growth and adhesion factors in recipient plasma before (pre), after (T0), 24 h and 3 weeks after HTx. Donor hearts were preserved either by ESHP (n=30) or SOC (n=22) procedures. Results Using unsupervised cluster analyses, the top 10 plasma cytokines and chemokines were identified, clearly separating T0 from other time points after HTx, reflecting a reperfusion injury-specific pattern. Surprisingly, ESHP or SOC heart preservation did not have a significant impact on these inflammatory plasma profiles at T0, T24 or 3 wks. The two strongest discriminators separating T0 from other time points i.e. IFN-γ, SCGF-β (all p≤0.05) were detected in both ESHP and SOC recipients at comparable concentrations. In contrast, the preservation method clearly affected the cytokine/chemokine profile in perfusates highlighted by higher concentrations of IL-6, IFN-γ, CXCL10, TNF-α, IL-10, IL-1RA, CXCL12, PDGF, G-CSF (all p≤0.05) in ESHP compared to SOC samples. Conclusion Although ESHP or SOC preservation did not affect the reperfusion response in plasma at T0 after HTx, normothermic oxygenated preservation of donor hearts was accompanied by secretion of pro- and anti-inflammatory cytokines, chemokines that may affect long-term functionality and longevity of the graft. With a better understanding of molecular changes during ESHP, we expect to identify biomarker candidates for improved organ function pre HTx.