Related Experiment Video
Updated: Sep 2, 2026
Cardiac Loading using Passive Left Atrial Pressurization and Passive Afterload for Graft Assessment
Published on: August 2, 2024
Ex Vivo Perfusion Unmasks a Proteomic Signature of Primary Graft Dysfunction in Donor Hearts
Selena S Li1, Bill Michaud1, Asishana A Osho2
1Department of Surgery, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts, USA.
Background:
Primary graft dysfunction (PGD) remains the leading cause of early mortality after heart transplantation and limits broader adoption of donation after circulatory death (DCD) hearts. Ex vivo heart perfusion (EVHP) provides a human platform to characterize molecular features associated with graft performance.
Objectives:
This study examines the circulating proteome during EVHP to determine potential markers or modulators of PGD in DCD hearts.
Methods:
The authors prospectively studied 37 human DCD hearts supported on EVHP. Perfusate was sampled at initiation (0-2 hours) and termination (3-6 hours) and profiled using a high-throughput proteomic platform (SOMAScan 11K). Ten PGD cases were propensity-matched to 10 non-PGD controls. Differential protein abundance and pathway enrichment analyses were performed.
Results:
At EVHP initiation, PGD hearts demonstrated enrichment of senescence-associated pathways (normalized enrichment score [NES]: 1.93; q < 0.01). By EVHP termination, proteomic profiles more clearly separated PGD from non-PGD hearts. PGD hearts exhibited broader proteomic remodeling, with 1,242 increased proteins (742 unique; q < 0.05) and 745 decreased proteins (619 unique; q < 0.05). Protein abundance was more dynamically associated with perfusion time in PGD hearts (33 proteins; median |ρ| = 0.78; q < 0.05) than in non-PGD hearts (3 proteins; median |ρ| = 0.83; q < 0.05). Pathway analysis revealed enrichment of apoptotic (NES: 1.75; q < 0.05) and catabolic programs (NES: 1.42; q < 0.05), with concurrent activation of inflammatory pathways (NES: 1.68; q < 0.05) in hearts destined to have PGD.
Conclusions:
PGD is defined less by baseline differences than by divergent proteomic trajectories during EVHP. Early enrichment of senescence-associated pathways is followed by coordinated activation of apoptotic and catabolic programs. These findings position EVHP as a physiological window for identifying molecular signatures of graft dysfunction and suggest an opportunity for targeted intervention in DCD donor hearts.
