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Updated: Jun 13, 2026
Functional Assessment of the Donor Heart During Ex Situ Perfusion: Insights from Pressure-Volume Loops and Surface Echocardiography
Published on: October 11, 2022
Ex vivo heart perfusion induces time dependent inflammatory activation in human donor hearts
Selena S Li1, Bill Michaud1, Asishana A Osho2
1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
Insights
Ex vivo heart perfusion (EVHP) of DCD hearts increases inflammation, with key cytokines like IL-6 rising over time. This innate immune response may explain graft dysfunction after heart transplantation.
Area of Science:
- Cardiovascular Biology
- Transplantation Immunology
- Proteomics
Background:
- Ex vivo heart perfusion (EVHP) enables using hearts from donors after circulatory death (DCD), but leads to higher rejection and dysfunction rates.
- The molecular changes induced by EVHP are not fully understood, impacting transplant outcomes.
Purpose of the Study:
- To define the molecular consequences of EVHP in DCD human hearts.
- To investigate the role of inflammation in EVHP-induced graft dysfunction.
Main Methods:
- Quantified 11,083 proteins in perfusate from human DCD hearts using aptamer-based proteomics.
- Validated findings in an independent human cohort and a swine DCD perfusion model.
Main Results:
- Identified significant upregulation of inflammatory cytokines IL-6, IL-8, and CCL2/MCP-1 during EVHP.
- Cytokine levels correlated with perfusion duration, indicating a time-dependent inflammatory response.
- Pathway analysis revealed enrichment of innate immune signaling and leukocyte chemotaxis.
Conclusions:
- EVHP triggers a conserved, time-dependent innate immune response in DCD hearts.
- Inflammatory activation during EVHP may be a key factor contributing to graft dysfunction post-transplant.
Abstract:
Ex vivo heart perfusion (EVHP) has enabled the use of hearts donated after circulatory death (DCD), expanding the donor pool but with persistently higher rates of rejection and graft dysfunction. The molecular consequences of EVHP, however, remain incompletely defined. We quantified 11,083 proteins in perfusate from 20 human DCD hearts undergoing EVHP using an aptamer-based proteomic platform. Among the most strongly upregulated proteins were inflammatory cytokines IL-6 (log₂FC = 3.5, FDR = 8.9 × 10-6), IL-8 (CXCL8; log₂FC = 2.8, FDR = 4.7 × 10-6), and CCL2/MCP-1 (log₂FC = 2.8, FDR = 2.0 × 10-6). Levels of these cytokines correlated strongly with perfusion duration (Spearman ρ = 0.77-0.78, FDR < 5 × 10-5). Pathway analysis demonstrated enrichment of innate immune signaling, including interleukin-1 signaling (normalized enrichment score (NES) = 2.14, adjusted p = 0.0016) and leukocyte chemotaxis pathways. These cytokine findings were validated in an independent human cohort using multiplex immunoassay and reproduced in a swine DCD perfusion model. Together, these data identify a conserved, time-dependent innate immune response during EVHP and suggest that inflammatory activation may represent one mechanism linking prolonged perfusion to graft dysfunction after DCD heart transplantation.
