Ischemia Injury and Ferroptosis in Human Donor Heart

What is the role of ferroptosis, programmed cell death characterized by intracellular iron accumulation and lipid peroxidation, in the context of ischemic injury related to heart transplantation? In this episode, Associate Editor Dr. Amanda LeBlanc (University of Louisville) interviews authors Dr. Kenneth Liao and Dr. Nandan Mondal (both at Baylor College of Medicine), along with expert Dr. Zachary Kiernan (Virginia Commonwealth University) about the latest study by Li et al. The authors found that prolonged cold storage increases the susceptibility of hearts donated after brain death (DBD) to ferroptotic cell death. In contrast, however, the authors found that warm ischemic injury increased the risk for ferroptotic cell death in hearts donated after circulatory death (DCD). Li et al. found that targeting ferroptosis could be beneficial for optimizing cold preservation for DBD hearts, while interventions for DCD hearts should focus on the early phase of warm ischemia. Heart transplantation is the gold standard therapy for patients with medically refractory advanced heart failure. However, demand greatly exceeds supply of donor hearts. Listen as we discuss the current state of the heart transplantation field and the many challenges it faces.

 

Shiyi Li, Katherine V. Nordick, Abdussalam E. Elsenousi, Rishav Bhattacharya, Randall P. Kirby, Adel M. Hassan, Camila Hochman-Mendez, Todd K. Rosengart, Kenneth K. Liao, and Nandan K. Mondal Warm-ischemia and Cold Storage Induced Modulation of Ferroptosis Observed in Human Hearts Donated After Circulatory Death and Brain Death Am J Physiol Heart Circ Physiol, published March 28, 2025. DOI: 10.1152/ajpheart.00806.2024