Language
English
Publication Date
1-1-2026
Journal
American Journal of Physiology Heart and Circulatory Physiology
DOI
10.1152/ajpheart.00705.2025
PMID
41401968
Abstract
This study compares myocardial injury responses in human donor hearts from donation after brain death (DBD) and donation after circulatory death (DCD), with a focus on myocardial membrane integrity, pyroptosis, and damage. Unlike DCD hearts, which are exposed to varying durations of functional warm ischemic time (fWIT), DBD hearts, which are never subjected to warm ischemia, served as controls. A total of 24 human hearts were procured, consisting of 6 from the DBD group and 18 from the DCD group. All procured hearts were placed in cold normal saline and stored for up to 6 h. Left ventricular biopsies were performed at 0, 2, 4, and 6 h to assess plasma membrane repair proteins (Annexin A1 and Dysferlin), pyroptosis markers [NOD-like receptor family, pyrin domain containing 3 (NLRP3), caspase-1, and N-terminal fragment of gasdermin D (GSDMD-NT)], and to evaluate edema and injury scores. Data suggest that DBD hearts maintained stable levels of plasma membrane repair proteins and showed no evidence of pyroptosis activation or significant injury throughout cold storage. In contrast, DCD hearts exhibited profound Annexin A1 depletion, early and progressive pyroptosis, elevated edema, and worsening histopathological injury, directly correlated with fWITs. These findings underscore that warm ischemia is a critical determinant of pyroptotic damage in donor hearts, and highlight the relative resistance of DBD hearts to such injury during preservation. For DCD hearts, strategies to enhance membrane repair capacity and inhibit pyroptosis during the fWIT phase should be the focus to maintain donor heart quality and suitability for transplantation.
Keywords
Humans, Heart Transplantation, Pyroptosis, Brain Death, Warm Ischemia, Male, Myocardium, Middle Aged, Female, Organ Preservation, Adult, Tissue Donors, Cell Membrane, Cold Ischemia, NLR Family, Pyrin Domain-Containing 3 Protein, Caspase 1, Time Factors, Aged, Gasdermins, Phosphate-Binding Proteins, cold storage, donation after brain death, donation after circulatory death, functional warm ischemia, myocardial pyroptotic cell death
Published Open-Access
yes
Recommended Citation
Li, Shiyi; Bhattacharya, Rishav; Elsenousi, Abdussalam E; et al., "Brain Death Versus Circulatory Death: How Functional Warm Ischemia and Cold Storage Impact Myocardial Membrane Repair in Human Donor Hearts" (2026). Faculty, Staff and Students Publications. 6125.
https://digitalcommons.library.tmc.edu/baylor_docs/6125