Cardiac graft protection in the brain dead donor

Background: Cardiac graft quality is altered by activation of systemic and intra-organ immune response due to hemodynamic and hormonal changes after donor brain death (BD). In earlier studies, effects on myocardial function after BD were elucidated. A higher risk for increased acute rejection episodes and impaired graft survival rates has been demonstrated in grafts from brain dead donors. Antithymocyte globulin (ATG) is an immunosuppressive drug that contains cytotoxic antibodies directed against antigens expressed on T-lymphocytes.

Methods: Female OF-1 mice (n = 16) were divided in 4 randomized groups ([BD-ATG], [BD-Control], [Therapy], [Control]). BD was induced with an intracranial balloon catheter, the mice were monitored for 6 h and the onset of BD was marked by an EEG-flatline. Myocardial tissue sections were analyzed by immunohistochemistry staining for IL-2 and IL-6.

Results: No structural changes after 6 h of observation could be demonstrated in our setting. We could not show significant inhibition of IL-2 and IL-6, interleukin expressions were comparable in all groups (n.s.). Notably, we observed a reduction of IL-6 deposition in ATG treated specimens compared to groups not receiving ATG before organ procurement (p = 0,06), regardless whether BD induction preceded or not. No IL-6 depositions were found in the coronary arteries of potential donors pretreated with ATG before organ procurement.

Conclusion: Other studies have shown significant amelioration of tissue damage after pretreatment with ATG before organ procurement, whereas our results were not significant. This study demonstrates the difficulties in accurate dosing and application of ATG. Our data may suggest that ATG is more effective in reducing the activation of IL-6 and its deposition in media myocytes of coronary arteries. Further investigations should be considered, as these findings may be relevant regarding possible measures to prevent later cardiac allograft vasculopathy.