Heart transplantation (HTx) is the ultimate treatment for end-stage heart failure. The number of patients on waiting lists for heart transplants, however, is much higher than the number of available organs. The shortage of donor hearts is a serious concern since the population affected by heart failure is constantly increasing. Furthermore, the long-term success of HTx poses some challenges despite the improvement in the management of the short-term complications and in the methods to limit graft rejection. Myocardial injury occurs during transplantation. Injury initiated in the donor as result of brain or cardiac death is exacerbated by organ procurement and storage, and is ultimately amplified by reperfusion injury at the time of transplantation. The innate immune system is a mechanism of first-line defense against pathogens and cell injury. Innate immunity is activated during myocardial injury and produces deleterious effects on the heart structure and function. Here, we briefly discuss the role of the innate immunity in the initiation of myocardial injury, with particular focus on the Toll-like receptors and inflammasome, and how to potentially expand the donor population by targeting the innate immune response.

The ultimate treatment for patients with end-stage heart failure is heart transplantation. The number of donor hearts which are primarily procured from donation after brain death (DBD) donors is limited, but donation after circulatory death (DCD) donor hearts can increase the heart donor pool. However, ischemia and reperfusion injuries associated with the DCD process causes myocardial damage, limiting the use of DCD hearts in transplantation. Addressing this problem is critical in the exploration of DCD hearts as suitable donor hearts for transplantation. In this study, rat hearts were procured following the control beating-heart donor (CBD) or DCD donation process. Changes in mitochondria and cardiac function from DCD hearts subjected to 25 or 35 minutes of ischemia followed by 60 minutes of reperfusion were compared to CBD hearts. Following ischemia, rates of oxidative phosphorylation and calcium retention capacity were progressively impaired in DCD hearts compared to CBD hearts. Reperfusion caused additional mitochondrial dysfunction in DCD hearts. Developed pressure, inotropy and lusitropy, were significantly reduced in DCD hearts compared to CBD hearts. We, therefore, suggest that interventional strategies targeted before the onset of ischemia and at reperfusion could protect mitochondria, thus potentially making DCD hearts suitable for heart transplantation.