title: Caspase-3-mediated splenic lymphocyte apoptosis in a porcine model of cardiac arrest.
abstract: BACKGROUND
  Postresuscitation immunologic dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood. The mitochondrial apoptosis pathway is initiated by the Bcl-2/Bax-controlled and caspase-3-mediated pathway, this study investigated whether mitochondrial pathway-mediated splenic lymphocyte apoptosis is involved in the postresuscitation immunosuppression in a porcine model of cardiac arrest.
  
  
  METHODS
  Twenty-eight Wuzhishan miniature pigs were randomly divided into 2 groups: return of spontaneous circulation (ROSC; n = 22) and sham-operated (n = 6). Return of spontaneous circulation was initiated after 8 minutes of untreated ventricular fibrillation. After successful ROSC, CD4(+) and CD8(+) lymphocyte subsets were determined by flow cytometry. Surviving pigs were randomly assigned to be humanely killed at 24 and 72 hours after ROSC (n = 8 per group). Spleens were removed for histopathologic analysis, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling assay.
  
  
  RESULTS
  A high degree of splenic lymphocyte apoptosis was observed in the ROSC group. Expression of Bax and activated caspase-3 was markedly increased in splenic tissue, whereas Bcl-2 was significantly decreased in the post-ROSC group compared with the sham-operated group (P < .05) at 24 and 72 hours after ROSC. The messenger RNA levels of activated caspase-3 of splenic tissue were significantly elevated at 24 and 72 hours after ROSC.
  
  
  CONCLUSIONS
  These results demonstrates that Bcl-2/Bax and caspase-3-mediated mitochondrial apoptosis signaling pathway may contribute to abnormal splenic lymphocyte apoptosis, which may be one of the main pathologic mechanisms of postresuscitation disturbance of immunologic function in a porcine model of cardiac arrest.
authors.affiliation: Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gu
authors.affiliation: Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Zhang
authors.affiliation: Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China.
authors.forename: WenPeng
authors.initials: W
authors.lastname: Yin
authors.affiliation: Department of Emergency Medicine, Beijing Chaoyang Hospital, Capital Medical University, Beijing, China. Electronic address: lcscyyy@163.com.
authors.forename: ChunSheng
authors.initials: C
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D018791:CD4 Lymphocyte Count; D015496:CD4-Positive T-Lymphocytes / Q000502:physiology; D018414:CD8-Positive T-Lymphocytes / Q000502:physiology; D053148:Caspase 3 / Q000502:physiology*; D004195:Disease Models, Animal; D005434:Flow Cytometry; D006323:Heart Arrest / Q000276:immunology / Q000503:physiopathology*; D008214:Lymphocytes / Q000502:physiology*; D008297:Male; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000502:physiology; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction / Q000502:physiology; D013154:Spleen / Q000166:cytology / Q000503:physiopathology*; D013552:Swine; D013556:Swine, Miniature; D051028:bcl-2-Associated X Protein / Q000502:physiology
chemical_list: D019253:Proto-Oncogene Proteins c-bcl-2; D051028:bcl-2-Associated X Protein; D053148:Caspase 3