Pathophysiological Changes and Systemic Inflammation in Brain Dead Organ Donors: Effect on Graft Quality

Abstract

Transplantation is the definitive treatment of end-stage organ disease. As the shortage of suitable organs poses its main limitation, the active management of potential organ donors becomes increasingly more important. The majority of solid organs are still obtained from donors after confirmed brain death. Brain death is the complete and irreversible cessation of all brain functions, and triggers a variety of severe pathophysiological changes in cardiovascular, hormonal and metabolic status that can result in organ damage. Moreover, brain death is associated with massive inflammatory response with a cytokine storm and complement activation that increases graft immunogenicity and adversely affects graft survival. Organs from brain-dead donors are more prone to graft dysfunction and rejection when compared to organs obtained from living donors. Brain death is thus believed to be an important risk factor influencing the quality of organs before procurement.

Connexins in endothelial cells as a therapeutic target for solid organ transplantation

“…During phase 1, various injurious events can target the donor organ's endothelium. Specifically, donor brain death exacerbates the release of harmful cytokines within the endothelial lining of the donor's vasculature 7 . Additionally, warm ischemia resulting from organ procurement from both standard criteria donors and those after circulatory death further damage the endothelial lining 8 .…”

“…Specifically, donor brain death exacerbates the release of harmful cytokines within the endothelial lining of the donor's vasculature. 7 Additionally, warm ischemia resulting from organ procurement from both standard criteria donors and those after circulatory death further damage the endothelial lining. 8 In phase 2, whether through pulsatile hypothermic perfusion or static cold storage, cold ischemia results in additive insults to the endothelial cells (ECs).…”