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

Conditions:Obesity Weight Loss, Cardiology
Therapuetic Areas:Cardiology / Vascular Diseases, Endocrinology
Age Range:18 - Any
Start Date:January 2016
End Date:June 2021
Contact:David B Seder, MD

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This is a prospective, observational study of inflammatory mechanisms and immune cell
activity after resuscitation from cardiac arrest during targeted temperature management.
Investigators are focusing on elucidating the activity of immune cells after resuscitation
and on biochemical pathways related to neuregulin-1 (a growth factor regulating cell
resistance to oxidative stress, cell survival and proliferation) and to lipid peroxidation
and pro-inflammatory lipid precursors. Participants will undergo blood sampling during 7 days
following cardiac arrest, and analyses performed. Patient characteristics, clinical
circumstances, and outcomes will be recorded and their associations with these inflammatory
pathways characterized.

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.

Inclusion Criteria:

- Survival >48 hours anticipated

- Informed consent from medicolegal POA within 12 hours of resuscitation

Exclusion Criteria:

- Not anticipated to survive at least 48 hours

- No available medicolegal POA or refuses consent

- Research team unavailable
We found this trial at
22 Bramhall St
Portland, Maine 04102
(207) 662-0111
Phone: 207-662-2179
Maine Medical Center One of the country's consistently highest rated hospitals is right in your...
Portland, ME
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