A High-Fidelity Porcine Model of Orthotopic Heart Transplantation Following Donation after Circulatory Death

The number of advanced heart failure patients who can receive a heart transplant is limited by a shortage of suitable organ donors. In efforts to expand the donor pool, alternative donation and procurement methods have been developed, including heart transplantation following donation after circulatory death (DCD HT). While short-term survival following DCD HT is non-inferior to heart transplantation with brain-dead donors, there may be an increased rate of primary graft dysfunction (PGD) associated with DCD HT allografts. The underlying etiology of PGD is multifactorial and incompletely understood. For DCD HT allografts, the period of warm ischemic injury during DCD procurement is a potential risk factor for PGD to which brain death allografts are not exposed. The functional warm ischemic time thus may be an important driver of PGD in DCD HT. However, the mechanisms underlying PGD in this clinical scenario are poorly understood at the molecular level. The work presented herein aims to describe the development and validation of a high-fidelity non-survival porcine model of DCD orthotopic heart transplantation. We hypothesize that the use of this translational large animal model is critical to elucidate molecular mechanisms contributing to PGD, as well as to investigate interventions designed to optimize allograft preservation and early performance. This model replicates the perioperative and surgical approach used in DCD HT clinically, with modifications to account for porcine anatomy and physiology. The development of this large animal surgical model will not only provide mechanistic insights into the development of PGD but also can be modified to enhance translational research efforts aimed at improving organ recovery following DCD HT.