NAD+ Enhances Postmortem Recovery of Murine DCD Hearts During Ex Vivo Oxygenated Organ Procurement

All articles of this category (opens in new window) Background: The global shortage of donor organs remains a critical challenge, with numerous patients dying on the waiting list. Maastricht category I poses significant challenges for DCD donation. Ex vivo heart perfusion shows great promise in enhancing organ viability and improving recovery. Recent studies show that NAD + protects against ischemia–reperfusion injury (IRI) in multiple organs by preserving mitochondrial function and reducing oxidative stress and inflammation. We recently developed a postmortem mouse heart recovery protocol using a modified recirculating oxygenated ex vivo perfusion system, substantially different from the classical Langendorff setup. The aim was to investigate the role of NAD + in DCD heart recovery using an ex vivo murine organ care system (OCS). Methods: Eight pooled C57BL/6 mice, aged 4 to 6 months, were subjected to cadaveric heart donation 1 hour postmortem after simulating failed resuscitation. The murine organ care system comprised a recirculating, normothermic ex vivo perfusion for 3 hours (maximum volume of 100 mL), oxygenated via an integrated membrane micro-oxygenator. Control hearts were perfused with KHL, while the experimental group received KHL enriched with NAD + at 2,000 μmol/L. Over a 3-hour period of ex vivo heart recovery, assessments included contractility, perfusion, gas and electrolyte profiles, total antioxidant capacity (TAC), cytokine expression, and apoptosis. Results: The functional recovery of all hearts began approximately 1 hour after reperfusion. The experimental hearts showed a significantly higher left ventricular developed pressure (dLVEP: 87.7 ± 19.8 vs. 19.5±) at 1, 2, and 3 hours of reperfusion ( p < 0.001). The slope of heart function exhaustion was also significantly better in the NAD + treated group. Surprisingly, TAC did not differ between the two groups. Nevertheless, the protective effect of NAD + against IRI and apoptosis was evident in the treatment group, as demonstrated by the lower expression of IL-6, IL-10, TNF-α, IL-23, GM-CSF, KC, JE, MIP-2, SDF-1, and TIMP-1 in comparison to control hearts. Conclusion: Using our murine protocol with NAD + treatment, DCD heart procurement improved contractility and recovery and reduced IRI within 4 hours postmortem. Implementation of NAD + treatment in DCD heart recovery is a promising way to increase the donor pool by mitigating IRI, reducing oxidative stress, apoptosis, and improving cellular energy metabolism. Publication History Article published online: 17 February 2026 © 2026. Thieme. All rights reserved. Georg Thieme Verlag KG Oswald-Hesse-Straße 50, 70469 Stuttgart, Germany