Activation of the heart by donor brain death accelerates acute rejection after transplantation

Background-Donor brain death upregulates expression of inflammatory mediato rs in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts f rom normal living donors. We examined the inflammatory and immunological co nsequences of gradual-onset donor brain death on cardiac allografts after t ransplantation. Methods and Results-Functioning hearts were engrafted from normotensive don ors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fish er, F344) were rejected significantly earlier (mean+/-SD, 9.3+/-0.6 days) b y their (Lewis) recipients than hearts from living donor controls (11.6+/-0 .7 days, P=0.03). The inflammatory response of such organs was accelerated, with rapid expression of cytokines, chemokines, and adhesion molecules and brisk infiltration of associated leukocyte populations. Upregulation of ma jor histocompatibility class II antigens increased organ immunogenicity. Ac ute rejection evolved in hearts from brain-dead donors more intensely and a t a significantly faster rate than in controls. Conclusions-Donor brain death is deleterious to transplanted hearts. The re sultant upregulation off inflammatory factors provokes host immune mechanis ms and accelerates the acute rejection process in unmodified hosts.