title: Immune status and apoptosis activation during brain death.
abstract: 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.
authors.affiliation: Intensive Care Unit, Delafontaine Hospital, Saint Denis, France.
authors.forename: Christophe
authors.initials: C
authors.lastname: Adrie
authors.forename: Mehran
authors.initials: M
authors.lastname: Monchi
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Fulgencio
authors.forename: Pascal
authors.initials: P
authors.lastname: Cottias
authors.forename: Hakim
authors.initials: H
authors.lastname: Haouache
authors.forename: Antonio
authors.initials: A
authors.lastname: Alvarez-Gonzalvez
authors.forename: Patrice
authors.initials: P
authors.lastname: Guerrini
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Cavaillon
authors.forename: Minou
authors.initials: M
authors.lastname: Adib-Conquy
mesh_terms: D000328:Adult; D000368:Aged; D017209:Apoptosis; D001926:Brain Death / Q000276:immunology / Q000503:physiopathology*; D053453:Caspase 9 / Q000378:metabolism; D006259:Craniocerebral Trauma / Q000276:immunology; D016207:Cytokines / Q000097:blood; D004731:Endotoxins / Q000097:blood; D005260:Female; D006085:Graft Survival; D006323:Heart Arrest / Q000276:immunology; D006801:Humans; D007249:Inflammation / Q000276:immunology*; D008297:Male; D008875:Middle Aged; D018482:Muscle, Skeletal / Q000503:physiopathology; D012333:RNA, Messenger / Q000378:metabolism; D020521:Stroke / Q000276:immunology; D009927:Tissue and Organ Procurement
chemical_list: D016207:Cytokines; D004731:Endotoxins; D012333:RNA, Messenger; D053453:Caspase 9