Severe primary graft dysfunction of the heart transplant is associated with increased plasma and intragraft proinflammatory cytokine expression.

Autor:	Holmström EJ; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland. Electronic address: emil.j.holmstrom@helsinki.fi., Syrjälä SO; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland; Department of Cardiothoracic Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland., Dhaygude K; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland., Tuuminen R; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland., Krebs R; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland., Nykänen A; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland; Department of Cardiothoracic Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland., Lemström KB; Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland; Department of Cardiothoracic Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
Jazyk:	angličtina
Zdroj:	The Journal of heart and lung transplantation : the official publication of the International Society for Heart Transplantation [J Heart Lung Transplant] 2023 Jun; Vol. 42 (6), pp. 807-818. Date of Electronic Publication: 2023 Jan 20.
DOI:	10.1016/j.healun.2023.01.005
Abstrakt:	Introduction: Heart transplant results have constantly improved but primary left ventricle graft dysfunction (LV-PGD) remains a devastating complication early after transplantation. Donor and recipient systemic inflammatory response may be involved in immune activation of the transplant, and LV-PGD development. Here, we investigated donor and recipient plasma and intragraft cytokine profiles preoperatively and during LV-PGD and searched for predictive markers for LV-PGD. Methods: Donor and recipient plasma samples (n = 74) and myocardial biopsies of heart transplants (n = 64) were analyzed. Plasma and intragraft cytokine levels were determined by multiplexed and next-generation sequencing platforms, respectively. The development of LV-PGD during the first 24 hours, and graft function and mortality up to 1 year after transplantation, were examined. Results: Severe LV-PGD, but not mild or moderate LV-PGD, was significantly associated with early mortality, plasma high-sensitivity troponin elevation, and an increase in intragraft and plasma proinflammatory cytokines during reperfusion. Preoperative donor and recipient plasma cytokine levels failed to predict LV-PGD. Cytokine network analysis identified interleukins -6, -8, -10, and -18 as key players during reperfusion. Prolonged cold and total ischemia time, and increased need for red blood cell transfusions during operation were identified as clinical risk factors for severe LV-PGD. Conclusions: Severe LV-PGD was associated with a poor clinical outcome. Donor and recipient plasma cytokine profile failed to predict LV-PGD, but severe LV-PGD was associated with an increase in post-reperfusion intragraft and recipient plasma proinflammatory cytokines. Identified key cytokines may be potential therapeutic targets to improve early and long-term outcomes after heart transplantation. (Copyright © 2023 International Society for Heart and Lung Transplantation. Published by Elsevier Inc. All rights reserved.)
Databáze:	MEDLINE
Externí odkaz:	Zobrazit plný text záznamu