Donor Brain Death Alters Plasma Protein Levels and is Dependent of Cause of Death

Background Currently, heart transplant (HTx) donors undergo invariably brain death prior to organ explantation. Brain death induces a systemic cytokine and catecholamine storm that lead to systemic inflammation, labile hemodynamics, and organ hypoperfusion. Together, these can damage the heart and aggravate later occurring graft injury, and ultimately, compromise graft function. However, the effect of etiology of donor cause of death on allograft outcome is not well understood. Methods We collected donor plasma samples and relevant clinical patient data from 52 HTx donor-recipient pairs. As controls, we collected plasma samples from 23 healthy volunteers. The patient cohort was collected in a separate prospective, blinded single-center trial. We measured donor and control plasma label-free quantification proteomics using liquid-chromatography mass spectrometry. We first compared plasma proteomics between brain dead donors and healthy controls, and then between donors with different causes of death. Results In the 54 donors, there were 26 spontaneous intracranial bleedings, 17 traumatic brain injuries, 6 anoxic brain injuries, and 3 non-classifiable causes of death (meningitis and two intoxications). We identified 272 proteins with altered plasma levels (P<0.05) after brain death when compared to healthy controls. In sub-group analysis, there were 74 proteins with significantly altered levels when donor causes of death were compared between each other. Conclusions We show that brain death alters protein expression, and that these changes are dependent on the cause of death. We are currently performing further molecular pathway analyses to characterize these changes in a systemic perspective. We believe that through proteomics we can identify novel treatment targets induced in noxious molecular pathways after brain death. The analyses will be presented at the TTS congress in 2018.