Viability of Partial Heart Transplant Grafts During Prolonged Cold Preservation Suggests That Longer Donor Cold Chain Logistics May Be Feasible.

Abstract

Background: Partial heart transplantation (PHT) is a new type of transplant that delivers growing heart valve implants for children. However, the acceptable ischemia time for PHTs remains unexplored. Therefore, the ischemia time for PHTs is empirically limited to orthotopic heart transplant (OHT) ischemia time of 4-6 h because the valves contained in OHTs are known to grow. This limits the distance from where PHT grafts can be procured. Without longer procurement distances, children who need PHT must wait a long time for suitable donor hearts. We previously demonstrated that PHTs remain viable for an ischemia time of 48 h in a rat model. Here we expand on this work in a porcine model.

Methods: Porcine pulmonary valve (PV) and aortic valve (AV) leaflets were preserved in DMEM culture medium, Belzer UW, Unisol, or HTK solution (n = 6/group) at 4°C. At preset intervals, the cellular viability was measured using the alamarBlue assay. The valves were also analyzed with flow cytometry and histology.

Results: While the metabolic activity of the valves slowly decreased over time, there was significant cellular viability for up to 21 days of cold preservation with Belzer UW solution. Flow cytometry and histology further corroborated the results, showing cellular preservation at 7 days of ischemia time.

Conclusions: OHT preservation is limited to only 4-6 h because longer ischemia times are associated with primary graft dysfunction from reduced contractility of ventricular myocardial cells. In contrast, PHTs spare the native ventricles. Our results indicate that PHT grafts remain viable much longer than OHT grafts. In vivo data are needed to verify that PHT grafts can grow and function after this significantly increased ischemic time.