Neuregulin-1, Lipidomics, and Inflammation After Resuscitation From Cardiac Arrest

Summary

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Description

Neuregulin-1 (NRG-1) is a growth factor that crucially regulates cell resistance to oxidative stress, cell survival and proliferation. In preliminary studies, investigators have found a novel role of NRG-1 in the regulation of pro-inflammatory activation of human mononuclear myeloid cells (monocytes...

Neuregulin-1 (NRG-1) is a growth factor that crucially regulates cell resistance to oxidative stress, cell survival and proliferation. In preliminary studies, investigators have found a novel role of NRG-1 in the regulation of pro-inflammatory activation of human mononuclear myeloid cells (monocytes and macrophages). These cells represent the major contributors to tissue perpetuation of inflammation. The investigators hypothesize that NRG-1 plays a role in the prevention of additional brain damage mediated by the post-cardiac arrest cell-mediated inflammatory response. To test the hypothesis, investigators will determine NRG-1 protein levels and NRG activity at different time points in peripheral blood of patients after resuscitation from cardiac arrest. Using flow cytometry, investigators will also investigate expression of ERBB (neuregulin) receptors on monocytes. The investigators will evaluate the relationships between circulating NRG-1, ERBB receptor expression, other markers of inflammation, duration of ischemic time, and biomarkers of the severity of neurological and cardiac injuries after cardiac arrest. Characterization of the immune response after cardiac arrest is a second aim of this project, with a focus on understanding the heterogeneity of cellular and humoral immune responses and how they relate to different phenotypes of post-resuscitation syndrome. A third focus is on inflammatory pathways related to lipid metabolism. An "obesity paradox" exists in cardiac arrest as in myocardial infarction and other diseases, in which mild or moderate obesity seems to be protective against mortality despite a higher incidence of adverse events during therapy. To characterize the role of lipids in the post-resuscitation inflammatory milieu, investigators will prospectively determine serial serum lipid profiles, and measure lipid peroxidation and pro-inflammatory lipid precursors in lean and obese post cardiac arrest patients. This will allow researchers to investigate the independent associations of body mass index (BMI), lipid profiles, lipid peroxidation, and pro-inflammatory lipid precursors with the post-resuscitation inflammatory state, and with functional outcomes. Participants will undergo a series of blood draws over 7 days, and standard 6 month follow up to assess functional outcomes. Investigators will be recording standard elements of postresuscitation care including demographics, clinical characteristics, laboratory values including biomarkers of neurological injury, and radiographic findings.

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