Abstract
Cardiac transplantation has become limited by a critical shortage of suitable organs from brain-dead donors. Reports describing the successful clinical transplantation of hearts donated after circulatory death (DCD) have recently emerged. Hearts from DCD donors suffer significant ischemic injury prior to organ procurement; therefore, the traditional approach to the transplantation of hearts from brain-dead donors is not applicable to the DCD context. Advances in our understanding of ischemic post-conditioning have facilitated the development of DCD heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement. The availability of a clinically approved ex situ heart perfusion device now allows DCD heart preservation in a normothermic beating state and minimizes exposure to incremental cold ischemia. This technology also facilitates assessments of organ viability to be undertaken prior to transplantation, thereby minimizing the risk of primary graft dysfunction. The application of a tailored approach to DCD heart transplantation that focuses on organ resuscitation at the time of procurement, ex situ preservation, and pre-transplant assessments of organ viability has facilitated the successful clinical application of DCD heart transplantation. The transplantation of hearts from DCD donors is now a clinical reality. Investigating ways to optimize the resuscitation, preservation, evaluation, and long-term outcomes is vital to ensure a broader application of DCD heart transplantation in the future.
Highlights
Institute, Australia Pasquale Pagliaro, Università degli Studi di Torino, Italy Serban C
Advances in our understanding of ischemic post-conditioning have facilitated the development of donated after circulatory death (DCD) heart resuscitation strategies that can be used to minimize ischemia-reperfusion injury at the time of organ procurement
Ischemic injury occurring during donation after brain death (DBD) heart transplantation has been linked to the development of graft vasculopathy and myocardial fibrosis [195,196,197], and further research is required to determine if similar sequelae will be observed with DCD hearts
Summary
Ischemia–Reperfusion Injury Understanding the physiologic impact of donor extubation and warm ischemia on the DCD heart is fundamental to developing a successful resuscitation strategy [24]. With this approach, a rapid cardiectomy is performed, the heart is connected to an ex situ heart perfusion (ESHP) device and preserved in a normothermic and beating state until eventual transplantation (Figure 3A) [22, 36]. Reperfusion at the time of organ procurement normalizes the extracellular pH, and creates a large hydrogen ion gradient across the plasma membrane that causes sodium influx via the NHE and calcium influx via reverse NCX (Figure 4B) Inhibiting these ionic fluxes early in the reperfusion period represents an important opportunity to limit hypercontracture and activation of the MPT pore (Figure 5) [49]. Further research is required to determine if one approach is superior to the other
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