Understanding donor heart preservation: Cellular mechanisms and clinical outcomes

Static cold storage (SCS) on ice has remained the gold standard preservation method for heart transplantation, and prolonged cold ischemia outside the typical 4-6 hour window is associated with an increased risk of primary graft dysfunction - a consequence attributed to ischemic damage and reperfusion injury. This, unfortunately limits the travel radius for donor heart procurement, a key factor that contributes to the overall shortage of donor organs. Recent research and clinical data have illustrated the validity of other preservation systems in preserving cardiac allografts, and many of these devices have shown promise in potentially prolonging the tolerated ischemic time beyond the accepted standard. Unfortunately, little is known regarding the biological basis of these preservation systems. In this review, we explore the existing knowledge of ischemic reperfusion injury as it relates to the donor heart. We also focus on characterizing the cellular and molecular mechanisms underlying existing donor heart preservation methods, including SCS, Paragonix' SherpaPak, TransMedics' Organ Care System, and XVIVO Heart Perfusion System, highlighting current limitations and areas for improvement. Furthermore, we describe the preclinical and clinical heart transplant outcomes related to Hypothermic Oxygenated Perfusate (HOPE) preservation.