The present study evaluates the role of the inflammatory status and apoptosis activation in the development of organ dysfunction after brain death using plasma assays and macroarray analysis on skeletal muscle biopsies to look for evidence of remote tissue damage in two intensive care units in France and one in Belgium. As controls, we used patients undergoing hip surgery and healthy volunteers. Causes of brain death in the 85 consecutive patients included in the study were cardiac arrest (n = 29; 34%), stroke (n = 42; 49%, with 38 patients having hemorrhagic stroke), and head injury (n = 14; 17%). Of the 85 patients, 45 donated 117 organs. Plasma endotoxin and cytokine levels indicated a marked systemic inflammatory response in brain-dead patients, which was strongest in the cardiac arrest group. Leukocyte dysfunction, as assessed by cytokines production in response to various stimuli, was noted in a subgroup of patients with brain death after stroke. Interestingly, skeletal muscle biopsies showed no increase in mRNAs for genes related to inflammation, whereas mRNAs for both antiapoptotic and proapoptotic genes were increased, the balance being in favor of apoptosis induction. The increased activation of the proapoptotic caspase 9 was further confirmed by Western blot. In conclusion, the presence of inflammation and apoptosis induction may explain the rapid organ dysfunction seen after brain death. Both abnormalities may play a role in organ dysfunction associated with brain death. However, the level of systemic inflammation or the presence of circulating endotoxin was not associated with lower graft survival.
*Intensive Care Unit, Delafontaine Hospital, Saint Denis; †Department of Physiology, Cochin Hospital, Paris Descartes University, AP-HP, Paris; ‡Intensive Care Unit, Jacques Cartier Institute, Massy, France; §Intensive Care Unit, Liège University Hospital, Liège, Belgium; ∥Intensive Care Unit, Tenon Hospital, AP-HP, Paris; ¶Surgical unit, Victor Dupouy's Hospital, Argenteuil; **Biomedicine Agency, Kremlin-Bicêtre Hospital, Le Kremlin Bicêtre; and ††Institut Pasteur, Unit Cytokines & Inflammation, Paris, France
Received 10 Jun 2009; first review completed 23 Jun 2009; accepted in final form 25 Jun 2009
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Conflict of Interest: Christophe Adrie received a grant from the publicly funded Biomedicine Agency, which manages organ donor data in France.