Thorac Cardiovasc Surg 2012; 60 - PP134
DOI: 10.1055/s-0031-1297781

ATG donor treatment reduces brain death triggered inflammatory graft activation

B Flörchinger 1, R Oberhuber 2, X Ge 3, YL Lee 3, C Schmid 1, S Tullius 3
  • 1Klinikum der Universität Regensburg, Klinik für Herz-, Thorax- und herznahe Gefäßchirurgie, Regensburg, Germany
  • 2Medizinische Universität Innsbruck, Klinik für Transplantations-, Viszeral- und Thorax-Chirurgie, Innsbruck, Austria
  • 3Brigham & Womens' Hospital, Harvard Medical School, Transplant Surgery Research Laboratory, Boston, United States

Aims: Donor brain death (BD) triggers inflammatory graft activation leading to impaired graft quality and outcome. We used a mouse brain death and heart transplantation model to dissect graft inflammation in wildtype (WT) and immune deficient (KO) donors and transferred this experimental setting to a clinically applicable model of donor T-cell depletion with thymoglobulin (ATG).

Method: Untreated wildtype C57BL6 mice, T-, B- and NK-cell deficient Rag2/double knockout mice, and thymoglobulin treated (25mg/kg i.p., immediately after BD induction) wildtype C57BL6 mice were ventilated for 3 hours after BD induction. Afterwards, hearts were engrafted into syngeneic recipients. After 72 hours, grafts and recipient spleens were assessed for systemic immune activation, expression of inflammatory cytokines and graft infiltration by FACS, PCR and histology analysis. Recipients of naïve hearts served as controls.

Results: Donor blood pressure levels after BD induction and graft ischemic times were comparable in all groups (p=n.s.).

Compared to WT controls, lymphocyte activation was increased in recipients of BD grafts (CD69: p<0.015). Recipients of immune deficient and thymoglobulin treated BD donor grafts featured significantly lower activation levels (p<0.049). Likewise, systemic as well as intra-graft levels of IL-1 (p<0.034), IL-6 (p<0.05), IFNγ (p<0.005), and TNFα (p<0.036) were significantly reduced in immune deficient and ATG treated graft recipients.

Grafts from untreated BD/WT donors showed severe lymphocyte infiltration. In contrast, grafts related to ATG treated BD/WT donors featured reduced cell infiltration, comparable to naïve WT controls.

Conclusion: Donor brain death triggers inflammatory graft activation, substantially mediated by donor immune cells. Thymoglobulin donor treatment alleviates graft activation after brain death.