Heart Transplantation From DCD donors: From the Bedside to the Bench

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Heart transplantation from adult donation after circulatory death (DCD) donors is an emerging area of clinical practice with 3 programs now having reported successful clinical outcomes using these donors.1-3 Posttransplant survival and graft function in almost 50 DCD heart transplants performed to date are comparable to those observed in contemporary heart transplants performed with hearts from donors who have undergone neurological determination of death.1-3
A major challenge with DCD heart donation which has prevented more widespread uptake has been the assessment of myocardial viability after death. With the DCD pathway, the heart is exposed to an unavoidable period of severe warm ischemia, the duration of which is extremely difficult to predict in advance.4 Approximately 1 in 4 potential DCD donors do not progress to death in time to allow organ donation to occur.4 Of those that do, the donor hemodynamic trajectory is highly variable after withdrawal of life support (WLS).5 This can make estimation of the onset of warm ischemia very difficult, particularly when there is a period of spontaneous breathing and hemodynamic stability before progression to cardiorespiratory arrest.5 When does organ ischemia begin in these donors? A definition of functional warm ischemia as the interval between systemic arterial systolic pressure of less than 50 mm Hg, and the administration of organ flush solution has been proposed for the lungs, liver, and kidneys of DCD donors.6 Experimental studies suggest that the onset of myocardial ischemia occurs well before systolic blood pressure falls below 50 mm Hg.7,8 Indeed, myocardial ischemia is likely to be the principle cause for the systolic blood pressure falling below 50 mm Hg.
Another confounding variable is the time between circulatory arrest and infusion of the organ preservation solution. This will be determined by several factors that are beyond the control of the retrieval team. These factors include the legislated “stand-off” time which varies anywhere from 2 to 20 minutes within and between countries that allow organ donation via the DCD pathway. Furthermore, the location of WLS may vary: from the intensive care unit, the anesthetic bay or the operating room depending on institutional policy. The shorter the mandated “standoff: time and the closer to the operating room that WLS takes place the shorter this postarrest time is likely to be. In our own program‘s experience, when the interval between circulatory arrest and donor heart flush (CADHF) was less than 15 minutes only 1 of 9 recipients required extracorporeal membrane oxygenation (ECMO) support for delayed graft function.9 In contrast, in all 4 instances where CADHF exceeded 15 minutes, the recipient required ECMO support. Although all hearts in this series ultimately regained normal function, the high rate of DGF in those hearts subjected to a CADHF longer than 15 minutes highlights the critical importance of this time interval in determining the extent of ischemic injury sustained by the DCD heart.
Using a porcine DCD model, Iyer and coinvestigators10 reported that as the CADHF time increased from 10 to 30 minutes, myocardial recovery dropped from 100% to 0%. They also reported that by modifying the composition of the flush solution, it was possible to mitigate the ischemic injury sustained by the DCD heart and extend the duration of tolerable warm ischemia by approximately 10 minutes. These experiments are labor-intensive and costly. There is a need for a small animal model that reliably mimics the clinical scenario. In this edition of the Journal, Kearns et al11 report their development of a rat model of DCD heart donation and normothermic ex vivo perfusion with a non–blood-containing physiological solution.

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