Xenotransplantation experiments in brain-dead human subjects–A critical appraisal

Brain-dead human subjects (decedents) were recently introduced as a potential pre-clinical experimental model in xenotransplantation. Brain death is associated with major pathophysiological changes, e.g., structural injury and cell infiltration in vital organs, and major hormonal, metabolic, inflammatory, and hemodynamic changes. In two of the three initial experiments, the design of the experiments resulted in little or no new information becoming available. In the third, the experiment was unfortunately unsuccessful as neither of the two pig kidneys transplanted into the decedent functioned adequately. Failure may well have been associated with the effects of brain death, but an immune/inflammatory response to the xenograft could not be excluded. Subsequently two further pig kidney transplants and two pig heart transplants have been carried out in human decedents, but again the data obtained do not add much to what is already known. In view of the profound changes that take place during and after brain death, it may prove difficult to determine whether graft failure or dysfunction results from the effects of brain death or from an immune/inflammatory response to the xenograft. A major concern is that, if the results are confusing, they may impact decisions relating to the introduction of clinical xenotransplantation.