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

Emil J Holmström; Simo O Syrjälä; Kishor Dhaygude; Raimo Tuuminen; Rainer Krebs; Antti Nykänen; Karl B Lemström

doi:10.1016/j.healun.2023.01.005

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

J Heart Lung Transplant. 2023 Jun;42(6):807-818. doi: 10.1016/j.healun.2023.01.005. Epub 2023 Jan 20.

Authors

Emil J Holmström¹, Simo O Syrjälä², Kishor Dhaygude³, Raimo Tuuminen³, Rainer Krebs³, Antti Nykänen², Karl B Lemström²

Affiliations

¹ Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland. Electronic address: emil.j.holmstrom@helsinki.fi.
² Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland; Department of Cardiothoracic Surgery, Helsinki University Hospital, and University of Helsinki, Helsinki, Finland.
³ Translational Immunology Research Program, Transplantation Laboratory, University of Helsinki, Helsinki, Finland.

PMID: 36754701
DOI: 10.1016/j.healun.2023.01.005

Abstract

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.

Keywords: acute rejection; cytokine response; heart transplantation; primary graft dysfunction.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Cytokines
Heart Transplantation* / adverse effects
Humans
Lung Transplantation* / adverse effects
Primary Graft Dysfunction* / etiology
Retrospective Studies
Risk Factors

Substances

Cytokines