Facilitating the improvement and enlargement of the donor pool in cardiothoracic transplantation

Heart and lung transplantation have become established treatment options for selected patients suffering from refractory end-stage heart and lung failure. However, the number of transplantations is limited due to the limited availability of suitable donor organs. In the cardiothoracic donor pool two subtypes of donation procedures are distinguished. One being donation after circulatory death (DCD) and the other being donation after brain death (DBD). With regards to organ preservation, the principal difference between a DCD and a DBD donor is that in the DBD donor both ventilation and blood circulation through organs are maintained up to the initiation of preservation of the organs. DBD organs are therefore not subjected to warm ischemic injury. In the DCD donor, the ventilation and blood circulation are already stopped prior to the initiation of preservation as a result of a withdrawal of life-sustaining therapy. With that, the organs are subjected to warm ischemia.The lungs are relatively tolerant to ischemia, whereas the heart is highly vulnerable to it. As a result of these characteristics, lungs and hearts encounter a different impact of a DBD or a DCD donation procedure. In turn, the technique used for preservation and the necessity to evaluate the organ ex situ after the donation procedure are dependent on both the donor organ and the donor type. Both ex vivo lung perfusion (EVLP) and ex situ heart perfusion (ESHP) play a key role in facilitating the enlargement and improvement of the donor pool, as a preservation technique, but also as a platform for functional assessment. The overall aim of this thesis was to explore and describe strategies to improve and enlarge the cardiothoracic donor pool. More specifically, the studies were designed to 1) describe and evaluate the implementation of both DCD lung transplantation and EVLP, 2) explore the potential of DCD heart donation for increasing the donor pool and 3) develop an ESHP strategy that facilitates preservation and assessment of donor hearts