*Purpose: Organ-specific differences are discussed for ischemia/reperfusion injury (IRI) in cardiothoracic transplantation (Tx) 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 (LTx), respectively, with respect to cytokines and endothelial markers in recipient blood and perfusates. Despite the evident clinical differences, our aim was to determine whether the microenvironment of HLTx patients would be rather related to HTx or LTx patients.

*Methods: Blood plasma pre Tx, at T0, T24 and perfusion solutions of 5 HLTx, 24 HTx and 26 LTx patients were analysed for cytokines and soluble endothelial markers using multiplex assays.

*Results: Early after transplantation at T0 and T24, HLTx and HTx recipients displayed significantly higher plasma levels of IL-6, CXCL8/IL-8, Ang-2, IGFBP-1, PAI-1 compared to LTx recipients that returned to baseline after three weeks. Identical kinetics with minimal changes were detected in the three groups for TNF, HB-EGF, EGF, PLGF, sFasL, TGF-a. Unsupervised cluster and principal component analyses clearly grouped HLTx and HTx patients together, separating LTx recipients apart with IGFBP-1, Ang-2, and PAI-1 as lead parameters (all p<0.01). In contrast, HLTx perfusates were grouped together with LTx and not HTx indicating that this compartment is dominated by the lung rather than the heart.

*Conclusions: A direct comparison of combined heart/lung with isolated heart or lung transplantation revealed that the early systemic IRI response of HLTx recipients is, perhaps counterintuitively, dominated by heart-associated endothelial markers like IGFBP-1, Ang-2, and PAI-1 which groups them together with HTx patients. The difference between recipient blood and perfusates provides strong evidence for an organ-specific impact on IRI with distinct heart- vs lung-associated signatures.

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