Ischemia Reperfusion Injury Significantly Differs between Lung vs. Heart Transplantation with Respect to Lead Cytokines and Correlation to Clinical Outcome
1Department of Cardiothoracic Transplantation and Vascular Surgery, Hannover Medical School, Hannover, Germany
2Institute of Transplant Immunology, Hannover Medical School, Hannover, Germany.
Meeting: 2018 American Transplant Congress
Abstract number: A39
Keywords: Heart preservation, Lung preservation
Session Information
Session Name: Poster Session A: Biomarkers, Immune Monitoring and Outcomes
Session Type: Poster Session
Date: Saturday, June 2, 2018
Session Time: 5:30pm-7:30pm
Presentation Time: 5:30pm-7:30pm
Location: Hall 4EF
Objectives
Ischemia reperfusion injury (IRI) is known to impair early graft function after lung (LTx) or heart (HTx) transplantation. We have previously characterized IRI in lungs recipients by a peak response directly after Tx. The lead cytokines involved in IRI after LTx were IL-6, CXCL8, CCL2. Since organ-specific aspects of IRI are not well understood, we aimed to define IRI in HTx and to find differences for this peak cresponse.
Methods
Plasma samples of LTx or HTx recipients were analysed preTx, at T0, T24, as well as respective perfusion solutions. 26 LTx recipients (mean age 49y) and 13 HTX recipients (mean age 47y) were included. Protein concentrations of 99 cytokines, chemokines, angiogenic factors were determined using multiplex assays. Clinical data, cold ischemic time (CIT), immunosuppression etc. were collected. Principal component (PCA), unsupervised cluster and K-network classifier (KNN) analyses were performed for the identification of the lead factors of IRI in LTx vs. HTx.
Results
KNN, unsupervised cluster and PCA analyses identified IL-6 as strongest signal for IRI in LTx recipients (preTx/T0 p<0.001) and high IL-6 levels correlated with PGD>2, CIT and PaO2/FiO2 ratio. In contrast, IL-10 was leading in HTx (preTx/T0 p<0.001), sufficient to discriminate between preTx and T0 plasma samples on its own. New statistics of LTx samples identified IL-10, IGFBP1, CXCL8, G-SCF, HGF and IL-16 (all p<0.01) as top discriminators. The overlap to HTx samples comprises IGFBP1, IL-16 (all p<0.001), but not IL-6. Instead, SCGF, M-CSF, VCAM, sVEGFR1, and the Tie2/Ang-2 and PAI-1/uPA ratios (all p<0.001) dominated the IRI response in HTx. These differences were also observed in perfusion solutions of hearts vs. lungs after standard cold preservation (all p<0.001).
Conclusion:
The comparison of soluble immune mediators in plasma of lung vs. heart recipients revealed significant differences in IRI response, especially regarding the lead cytokines IL-6 and IL-10. These differences are likely to reflect organ-specific components in IRI. Thus, different biomarker candidates may be useful to define IRI in lung vs. heart transplant patients.
CITATION INFORMATION: Wiegmann B., Ledwoch N., ISke J., Neudörfl C., Tudorache I., Kühn C., Kaufeld T., Ius F., Rojas S., Avsar M., Haverich A., Warnwcke G., Falk C. Ischemia Reperfusion Injury Significantly Differs between Lung vs. Heart Transplantation with Respect to Lead Cytokines and Correlation to Clinical Outcome Am J Transplant. 2017;17 (suppl 3).
To cite this abstract in AMA style:
Wiegmann B, Ledwoch N, ISke J, Neudörfl C, Tudorache I, Kühn C, Kaufeld T, Ius F, Rojas S, Avsar M, Haverich A, Warnwcke G, Falk C. Ischemia Reperfusion Injury Significantly Differs between Lung vs. Heart Transplantation with Respect to Lead Cytokines and Correlation to Clinical Outcome [abstract]. https://atcmeetingabstracts.com/abstract/ischemia-reperfusion-injury-significantly-differs-between-lung-vs-heart-transplantation-with-respect-to-lead-cytokines-and-correlation-to-clinical-outcome/. Accessed May 8, 2025.« Back to 2018 American Transplant Congress