In:
Circulation, Ovid Technologies (Wolters Kluwer Health), Vol. 148, No. Suppl_1 ( 2023-11-07)
Abstract:
Introduction: Chemokines mediate the entrance and migration of leukocytes to inflamed tissue areas, contributing to the intensity of local inflammation. We found a high level of circulating chemokines, CCL2, CCL4, and CCL23, in patients resuscitated after cardiac arrest (CA). Hypothesis: The level of circulating chemokines is associated with systemic immune cell response, neurologic injury, and outcome after cardiac arrest. Goal: To characterize temporal chemokine and immune cell responses to cardiac arrest. Methods: A total of 42 patients after CA and 22 control subjects who underwent coronary artery bypass grafting (CABG) were enrolled. ELISA was used to determine chemokines in plasma at 6 hr, 24 hr, 48 hr, and 72 hr after CA and in CABG patients pre-operatively. Flow cytometry was used to determine subpopulations of immune cells. We measured changes in chemokines over time and the association of chemokine levels with outcome, markers of inflammation, and brain injury. A mouse model of CA was employed to assess the activation of human neutrophils locally in brain tissue. Results: Temporal dynamics were different for each chemokine, with early increases in CCL2 and CCL4, followed by a late elevation in CCL23 at 48 hours after resuscitation. A higher level of CCL23 was associated with a worse cerebral performance category score (r s =0.3, p=0.042) and higher mortality (r s =0.3, p=0.039). Positive correlations were found between CCL23 and an increased number of neutrophils, cellular mediators of inflammation, and levels of neuron-specific enolase. To study the potential role of neutrophil activation locally in injured brain tissue, we injected human post-CA neutrophils into the bloodstream of successfully resuscitated mice and measured the CCL23 in human neutrophils in mouse blood and brain 24 hours after resuscitation. An increased level of CCL23 production was found in mouse brain neutrophils compared to those in the peripheral circulation. Conclusion: It is well known that an early intense inflammatory response is associated with poor outcomes after CA. Our new data indicate that late activation of neutrophils in brain tissue may represent an additional mechanism contributing to ongoing brain tissue injury via the production of CCL23 after cardiac arrest.
Type of Medium:
Online Resource
ISSN:
0009-7322
,
1524-4539
DOI:
10.1161/circ.148.suppl_1.170
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2023
detail.hit.zdb_id:
1466401-X
detail.hit.zdb_id:
80099-5
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