Glucocorticoid receptor expression in patients with cardiac arrest in the early period after the return of spontaneous circulation: a prospective observational single-centre study

Abstract

ObjectivesRapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest (CA) syndrome. However, GC receptor (GR) expression changes have not been studied. Hence, this study aimed to investigate the association of early changes in GR expression and prognosis and immune response in patients who experienced CA.DesignProspective observational study.SettingEmergency department.ParticipantsPatients (85) in the early period of return of spontaneous circulation (ROSC) after CA were admitted between October 2018 and October 2019. After a physical examination, age-matched and sex-matched healthy individuals (40) were recruited for the control group.Primary and secondary outcome measuresGR expression and cell counts of circulatory T and B lymphocytes, natural killer cells and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were also tested.ResultsAll cell counts were lower, and plasma total cortisol levels were higher (p<0.001) in patients who experienced CA than in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes were not significantly different, but the mean fluorescence intensity and GR expression in other cells were lower in patients who experienced CA (p<0.05) than in the healthy control group. ACTH levels were not different. There were no significant differences between survivors and non-survivors.ConclusionsThis study revealed that GR expression and cell counts rapidly decreased, whereas plasma total cortisol levels increased in the early period after ROSC among patients who experienced CA. Our findings provide important information about GR level and function, and immunosuppressive status in these patients. Assessing GR expression in patients who experienced CA may help screening for those who are more sensitive to GC therapy.

A critical reappraisal of vasopressin and steroids in in-hospital cardiac arrest

“…Consequently, prolonged ischemia time (followed by reperfusion) is associated with greater, intracellular, oxidative stress [ 13 ], and likely, more extensive oxidation and loss of function [ 12 ] of various proteins, including the GR. Accordingly, a recent study reported rapid, post-ROSC decline in B/T lymphocyte GR-expression [ 14 ].…”

Therapeutic potential of mitochondrial transplantation in modulating immune responses post-cardiac arrest: a narrative review

“…These steroids appear to lower inflammation by decreasing pro-inflammatory cytokines [ 60 , 61 ]. Further, a prospective observational single-center study focused the immune responses and glucocorticoid receptor expression in patients with CA [ 62 ]. The study revealed that CA survivors exhibit lower glucocorticoid receptor levels in leukocytes, especially those with prolonged CA and adverse neurological outcomes, linking receptor downregulation with increased inflammation [ 62 ].…”

“…Further, a prospective observational single-center study focused the immune responses and glucocorticoid receptor expression in patients with CA [ 62 ]. The study revealed that CA survivors exhibit lower glucocorticoid receptor levels in leukocytes, especially those with prolonged CA and adverse neurological outcomes, linking receptor downregulation with increased inflammation [ 62 ]. This suggests that early post-CA corticosteroid therapy might help regulate immune responses and improve patient outcomes by normalizing glucocorticoid receptor activity.…”