Preserving and evaluating hearts with ex vivo machine perfusion: an avenue to improve early graft performance and expand the donor pool☆

Abstract

Cardiac transplantation remains the first choice for the surgical treatment of end stage heart failure. An inadequate supply of donor grafts that meet existing criteria has limited the application of this therapy to suitable candidates and increased interest in extended criteria donors. Although cold storage (CS) is a time-tested method for the preservation of hearts during the ex vivo transport interval, its disadvantages are highlighted in hearts from the extended criteria donor. In contrast, transport of high-risk hearts using hypothermic machine perfusion (MP) provides continuous support of aerobic metabolism and ongoing washout of metabolic byproducts. Perhaps more importantly, monitoring the organ's response to this intervention provides insight into the viability of a heart initially deemed as extended criteria. Obviously, ex vivo MP introduces challenges, such as ensuring homogeneous tissue perfusion and avoiding myocardial edema. Though numerous groups have experimented with this technology, the best perfusate and perfusion parameters needed to achieve optimal results remain unclear. In the present review, we outline the benefits of ex vivo MP with particular attention to how the challenges can be addressed in order to achieve the most consistent results in a large animal model of the ideal heart donor. We provide evidence that MP can be used to resuscitate and evaluate hearts from animal and human extended criteria donors, including the non-heart beating donor, which we feel is the most compelling argument for why this technology is likely to impact the donor pool.

Advances in Machine Perfusion Graft Viability Assessment in Kidney, Liver, Pancreas, Lung, and Heart Transplant

“…One of the main reported disadvantages in the animal studies is the association of MP with increased myocardial edema, 115 with some studies showing a variation depending on the preservation solution. [116][117][118][119] This association is thought to be mediated by MPdependent hydrostatic pressure and perfusate colloid oncotic pressure and further compounded by the lack of lymphatic flow to the arrested heart. 118 Collins and associates suggested that lack of physiological variation in coronary artery flow and pressures also may contribute to edema formation, 118 which is thought to be associated with impaired posttransplant diastolic function recovery.…”

“…[116][117][118][119] This association is thought to be mediated by MPdependent hydrostatic pressure and perfusate colloid oncotic pressure and further compounded by the lack of lymphatic flow to the arrested heart. 118 Collins and associates suggested that lack of physiological variation in coronary artery flow and pressures also may contribute to edema formation, 118 which is thought to be associated with impaired posttransplant diastolic function recovery. 115 More recently, Ozeki and associates suggested that increased edema may only be transient.…”

Ex vivo Approach to Treat Failing Organs: Expanding the Limits

“…Continuous machine perfusion of donor hearts has been proposed as an alternative and superior method of donor heart preservation compared to cold static storage [16]. Continuous ex vivo heart perfusion demonstrated a beneficial influence on aerobic metabolism during the preservation of the donor heart by maintaining cell integrity and vital cell function [17].…”

Optimization of Cooling Protocols for Hearts Destined for Transplantation

“…Collins et al [6,20] reported cases in which hearts were successfully resuscitated by hypothermic machine perfusion with full recovery of function. They could also resuscitate one of the two hearts which belonged to Non Beating Heart Donors (NBHDs).…”

“…The above zones were implemented to facilitate transplant coordination and to minimize ischemic time [6]. More information about prioritized match candidates based on the level of urgency for transplantation can be found in OPTN policies [4].…”