The Reperfusion Response in Plasma of Combined Heart/ Lung Transplanted Patients is Guided by Heart-Associated Cytokine Patterns on Contrast to the Ischemic Injury in Perfusion Solutions Following a Lung-Associated Pattern
1MHH, Institute of Transplant Immunology, Hannover, Germany, 2Institute of Transplant Immunology, Hannover Medical School MHH, Hannover, Germany, 3Department of Cardiothoracic, Transplantation and Vascular Surgery, Hannover Medical School MHH, Hannover, Germany
Meeting: 2020 American Transplant Congress
Abstract number: B-265
Keywords: Heart/lung transplantation, Immunogenicity, Inflammation, Perfusion solutions
Session Information
Session Name: Poster Session B: Heart and VADs: All Topics
Session Type: Poster Session
Date: Saturday, May 30, 2020
Session Time: 3:15pm-4:00pm
Presentation Time: 3:30pm-4:00pm
Location: Virtual
*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 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 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 weeks as well as perfusion solutions (taken from the storage bags at the end of cold ischemia) of 5 HLTx, 24 HTx and 21 LuTx patients were analysed 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 that returned to baseline after three weeks. Endoglin, IL-18, sFASL, TNF-α, VEGF-A, -C, -D, HB-EGF, EGF uPA and PIA-1 contributed to the discriminative pattern between the three groups with similar kinetics of a significant increase at T0 (all p<0.01). In sharp contrast, HLTx perfusates were grouped together with LuTx and not HTx based on their significantly higher levels IGFBP-1, PAI-1, IL-6 and others 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 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.
To cite this abstract in AMA style:
Falk C, Kühne J, Radomsky L, Wandrer F, Wiegmann B, Ledwoch N, Keil J, Beushausen K, Ius F, Sommer W, Rojas-Hernandez S, Tudorache I, Haverich A, Warnecke G. The Reperfusion Response in Plasma of Combined Heart/ Lung Transplanted Patients is Guided by Heart-Associated Cytokine Patterns on Contrast to the Ischemic Injury in Perfusion Solutions Following a Lung-Associated Pattern [abstract]. Am J Transplant. 2020; 20 (suppl 3). https://atcmeetingabstracts.com/abstract/the-reperfusion-response-in-plasma-of-combined-heart-lung-transplanted-patients-is-guided-by-heart-associated-cytokine-patterns-on-contrast-to-the-ischemic-injury-in-perfusion-solutions-following-a-l/. Accessed May 16, 2025.« Back to 2020 American Transplant Congress