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Background: Postresuscitation immunological dysfunction contributes to the low survival rate after successful resuscitation, but its mechanism remains poorly understood.This study investigated whether caspase-3-mediated splenic lymphocytes apoptosis is involved in the postresuscitation immunosuppression in a porcine model of cardiac arrest.Methods: 28 Wuzhishan miniature pigs were randomly divided into return of spontaneous circulation (ROSC) group (n=22) and sham-operated group (n=6), After 8 min of untreated ventricular fibrillation and 2 min of basic life support, After successful ROSC, CD4+ and CD8+ lymphocyte subsets was determined by flow cytometry.Surviving pigs were randomly assigned to be killed (n =8 per group) at 24 and 72 h after ROSC, Following this, the spleens were removed for observing the histopathological changes and western blotting, quantitative real-time PCR, and terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) assay.Results: CD4+ lymphocyte subsets and CD4+/CD8+was significantly lower in the post-ROSC group compared with the sham-operated group (P <.05) at 12 and 72 h after ROSC.High degree of splenic lymphocyte apoptosis was observed in the ROSC group.Meanwhile, expression of Bax, and caspase-3 protein of splenic tissue was markedly increased, while 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, Furthermore, the mRNA levels of caspase-3 of splenic tissue were significantly elevated at 24 and 72 h afar ROSC, suggesting that the mitochondrial apoptotic pathway was switched to a pro-apoptotic response.Conclusion: These results demonstrates that caspase-3-mediated apoptosis signal pathway may contribute to abnormal splenic lymphocyte apoptosis,which may be one of the main pathological mechanisms of postresuscitation disturbance of immunological function in a porcine model of cardiac arrest.