Abstract

Introduction: Immature neutrophils mobilized from bone marrow in response to injury do not express CD10 and are characterized as pro-inflammatory. Maturity status of neutrophils has not yet been described in patients after the global ischemic-reperfusion injury following cardiac arrest (CA). Hypothesis: Immature neutrophils predominate the systemic cellular response after CA and are associated with mortality. Goal: To characterize neutrophils and their associations with clinical parameters in patients following resuscitation from CA. Methods: After informed consent, 100 subjects were enrolled. Blood samples were collected at 6, 12, 24, 48, 72, and 168 hours after return of spontaneous circulation (ROSC). White blood cells (WBC) were isolated and stained for flow cytometry. Data analysis was performed with FlowJo and GraphPad Prism; a P-value of <0.05 was deemed statistically significant. Results: In our cohort of 51 non-survivors and 49 survivors, there were no significant differences in WBC count at any time point. At 72 hours after ROSC, we found a higher absolute number (6.8 vs. 5.0; p=0.018) and percentage ( 87.1 vs. 80.3; p=0.030) of neutrophils in the WBC population in non-survivors compared to survivors. Analysis of neutrophil CD10 subpopulations revealed a higher number of immature CD10 - neutrophils in non-survivors at 72 hours after ROSC (6.1 vs. 4.4; p=0.007) compared to survivors. There was no significant difference between non-survivors and survivors in mature CD10 + neutrophil count or temporal changes. The CD10 - /CD10 + neutrophil ratio was significantly higher in non-survivors at 24 hours (4.7 vs. 3.1; p=0.036) and 48 hours (11.5 vs. 6.6; p=0.040) after ROSC. Conclusions: Neutrophils are important to inflammation resolution after injury; however certain subpopulations of immune cells may be involved in and perpetuate tissue damage after CA. The levels and temporal changes of pro-inflammatory, immature (CD10 - ) neutrophils in non-survivors point to the need for further research including functional studies. The identification of neutrophil marker targets that may impact the balance of pro- and anti-inflammatory immune cells and their related signaling pathways could offer opportunities to improve outcomes after cardiac arrest.

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