In Combined Heart/Lung Transplantation, the Reperfusion Response in Recipients is Dominated by Heart-Associated Cytokine and Endothelial Patterns While the Ischemic Injury in the Storage Solution is Dominated by a Lung-Associated Microenvironment

Purpose Organ-specific differences are discussed for ischemia/reperfusion injury (IRI) in cardiothoracic transplantation but rarely compared directly in a clinical setting. Therefore, we compared a cohort of combined heart/lung transplants (HLTx) with cohorts of isolated heart (HTx) or lung transplantations (LuTx), respectively, with regards to cytokines and endothelial markers in recipient blood and perfusates. Our aim was to determine whether the microenvironment of HLTx patients and perfusates would be rather related to the HTx or LuTx setting. Methods Blood plasma pre Tx and post Tx at T0, T24 and 3 wks as well as perfusion solutions (taken from storage bags at the end of cold ischemia) of 5 HLTx, 24 HTx and 21 LuTx patients were analyzed for cytokines, chemokines and soluble endothelial markers (60 proteins) using multiplex assays. Results Early after transplantation at T0 and T24, HLTx and HTx were clustered together and separated from LuTx recipients based on their significantly higher plasma levels of IL-6, CXCL8/IL-8, Ang-2, IGFBP-1, PAI-1 compared to LTx recipients. Endoglin, IL-18, sFASL, TNF-α, VEGF-A, -C, -D, HB-EGF, EGF, uPA and PAI-1 contributed to the discriminative pattern between the three groups with similar kinetics of a significant increase at T0 (all p Conclusion A direct comparison of combined heart/lung with isolated heart or lung transplantation revealed that the early systemic reperfusion response of HLTx recipients in blood is dominated by heart-associated endothelial markers like IGFBP-1, Ang-2, and PAI-1 which groups them together with HTx patients. In contrast, the ischemic damage pattern of HLTx perfusates was clustering closer to lung than to heart perfusates. These differences between recipient blood and perfusates strongly suggest that the ischemia response is dominated by lung whereas the systemic reperfusion response is guided by heart. These results underline the organ-specific impact on IRI with distinct heart- vs lung-associated signatures.