Physiological Function of Blood Vessels from Uncontrolled Donation after Circulatory Death in Pigs

Abstract

Donation after circulatory death (DCD) has become increasingly important in kidney transplantation. Challenges, including early graft loss and delayed graft function, remain. Little is known regarding vascular properties. The aim was to examine effects of DCD on renal artery function in a novel pig extended DCD model, extending the time from circulatory arrest to retrieval of the organ to more than 4 hours, making it more feasible to recruit more organs from DCD. Renal and iliac arteries were obtained from animals immediately after euthanasia (fresh) and 4.5hr after DCD. Vessels were also analyzed after 10hr at 4°C in physiological salt solution (stored). Preparations were mounted for isometric force recording in vitro and examined at optimal stretch for active tension. Iliac arteries were more sensitive to noradrenaline compared to renal artery, possibly reflecting differences in sympathetic control of perfusion in renal and hind limb vascular beds. Active tension (depolarization, noradrenaline activation) was significantly lower in DCD renal arteries compared to fresh vessels. Stored renal arteries were also weaker, but to a lower extent, whereas iliac artery was only marginally weakened in uDCD and unaffected by storage. For both vessel types, DCD caused a significant attenuation of endothelial-mediated relaxation. Kidneys from uDCD donors performed poorly after transplantation, as expected, with a somewhat better result if the donor was given the standard protocol, including cooling after two hours. In conclusion, DCD introduces changes both in contractile function and endothelium-mediated relaxation of renal arteries. Effects were more pronounced than in iliac artery, suggesting that DCD could be one factor affecting the functional circulation of the donor kidney after transplantation. Further studies of uDCD subject to reconditioning before transplantation is underway to study the reversibility of changes to the endothelial function after our uDCD protocol.