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(Circulation. 2000;102:2426.)
© 2000 American Heart Association, Inc.

Basic Science Reports

Activation of the Heart by Donor Brain Death Accelerates Acute Rejection After Transplantation

Markus J. Wilhelm, MD; Johann Pratschke, MD; Francisca Beato, BS; Maarten Taal, MD; Mamoru Kusaka, MD; Wayne W. Hancock, MD, PhD; Nicholas L. Tilney, MD

From the Surgical Research Laboratory, Harvard Medical School and the Department of Surgery, Brigham and Women’s Hospital (M.J.W., J.P., M.K., N.L.T.); the Department of Medicine, Renal Division, Brigham and Women’s Hospital (F.B., M.T.); and Millenium Inc, Cambridge, Mass, and Department of Pathology, Harvard Medical School (W.W.H.), Boston, Mass. Dr Wilhelm is now at the Department of Cardiothoracic Surgery, University of Muenster, Germany.

Correspondence to Nicholas L. Tilney, MD, Surgical Research Laboratory, E-1, Room 142, Harvard Medical School, 260 Longwood Ave, Boston, MA 02115. E-mail bhayslett{at}rics.bwh.harvard.edu

Background—Donor brain death upregulates expression of inflammatory mediators in the heart. It is hypothesized that these nonspecific changes trigger and amplify acute rejection in unmodified recipients compared with hearts from normal living donors. We examined the inflammatory and immunological consequences of gradual-onset donor brain death on cardiac allografts after transplantation.

Methods and Results—Functioning hearts were engrafted from normotensive donors after 6 hours of ventilatory support. Hearts from brain-dead rats (Fisher, F344) were rejected significantly earlier (mean±SD, 9.3±0.6 days) by 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 major histocompatibility class II antigens increased organ immunogenicity. Acute rejection evolved in hearts from brain-dead donors more intensely and at a significantly faster rate than in controls.

Conclusions—Donor brain death is deleterious to transplanted hearts. The resultant upregulation of inflammatory factors provokes host immune mechanisms and accelerates the acute rejection process in unmodified hosts.

Key Words: brain • transplantation • inflammation • rejection

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