Expression of Glucocorticoid Receptors in the Early Period After the Return of Spontaneous Circulation Among Patients Who Experienced Cardiac Arrest : A Retrospective Observational Study

Author(s):  
Yanan Yu ◽  
Ziren Tang ◽  
Jiabao Li ◽  
Miaorong Xie ◽  
Chenchen Hang ◽  
...  

Abstract Background: Rapid changes in glucocorticoid (GC) levels and adrenal insufficiency are related to the development of post-cardiac arrest syndrome. However, changes in glucocorticoid receptors (GR) have not been studied. Hence, this study aimed to investigate the association of early changes in GR and prognosis and immune response in patients who experienced cardiac arrest (CA). Methods: In this observational single-center case-control study, we enrolled patients who were in the early period of return of spontaneous circulation after CA and were admitted to the emergency department of the Beijing Chaoyang Hospital between October 2018 and October 2019. Age- and sex-matched healthy individuals were recruited for the control group after a physical examination.GR expression and cell counts of circulatory T and B lymphocytes, natural killer, and regulatory T (Treg) cells were assessed. Plasma total cortisol and adrenocorticotrophic hormone (ACTH) levels were tested. Since the data for total cortisol and ACTH levels had a skewed distribution, we compared our results with the natural logarithmic conversion values after adding 1 (ln [total cortisol+ 1], ln [ACTH+ 1]). Measurement data with a skewed distribution are expressed as medians (25th and 75th percentiles). The Mann–Whitney U test was used to compare variables between groups. The qualitative parameters in the 2 × 2 contingency table were used for analysis.Results: Overall, 85 patients who experienced CA and 40 healthy individuals were enrolled. All cell counts were lower and plasma total cortisol levels were higher (P<0.001) in patients who experienced CA than those in the healthy control group. GR expression in Treg cells and CD3+CD4+ T lymphocytes was 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 those in the healthy control group. ACTH levels did not show any difference. There were no significant differences between survivors and non-survivors. Conclusion: Our findings provide insights into GC sensitivity and immunosuppressive status in these patients, and a new perspective for GC targeted treatment.

2020 ◽  
Author(s):  
Yanan Yu ◽  
Chunsheng Li ◽  
Miaorong Xie ◽  
Ziren Tang ◽  
Jiabao Li ◽  
...  

Abstract Background: In patients with immune disorders, the role of T-helper (Th) cells immediately following the return of spontaneous circulation (ROSC) after cardiac arrest is unclear. We evaluated the influence of plasma cytokine and programmed cell death-1 (PD-1) expression on circulating Th1 and Th2 cells and elucidated their role in immune function immediately following ROSC. Methods: We enrolled 92 non-consecutive cardiac arrest patients that experienced ROSC between 6 and 24 h post-cardiac arrest as well as 40 healthy controls. Outcome data were collected 28 days after ROSC. Peripheral blood samples were analyzed to determine Th1 and Th2 cell counts and PD-1 expression. The plasma levels of cytokines, including interferon-γ, tumor necrosis factor-α, interleukin (IL)-4, IL-6, and IL-10 were determined. Results: Compared with those in healthy individuals, Th1 and Th2 cell counts and Th1/Th2 cell ratios in CA patients after ROSC were significantly reduced (P < 0.05). The percentages of PD-1 expression were significantly higher in Th1 and Th2 cells (P < 0.01). There were no significant differences in Th1 and Th2 cell expression of PD-1 between survivors and non-survivors. Plasma levels of IL-6 and IL-10 in ROSC patients were significantly higher during the early period (P < 0.05). Conclusions: Th1 and Th2 cell expression of PD-1 is upregulated in the period immediately following ROSC in cardiac arrest patients and may be responsible for the observed immunosuppression in these patients during this period.


Circulation ◽  
2020 ◽  
Vol 142 (Suppl_4) ◽  
Author(s):  
Matt Oberdier ◽  
Jing Li ◽  
Dan Ambinder ◽  
Xiangdong Zhu ◽  
Sarah Fink ◽  
...  

Background: Out-of-hospital sudden cardiac arrest is a leading cause of death in the United States, affecting over 350,000 people per year with an overall survival rate around 10%. CPR, defibrillation, and therapeutic hypothermia are common resuscitation strategies, but hypothermia is difficult to implement timely to achieve survival benefit. A cell-permeable peptide TAT-PHLPP9c has been shown to alter metabolic pathways similar to hypothermia, and decreases the release of two biomarkers, taurine and glutamate, during the high osmotic stress of heart stunning and brain injury in a mouse arrest model. Hypothesis: TAT-PHLPP9c, given during CPR, enhances 24-hour survival in a swine ventricular fibrillation (VF) model. Methods: In 14 (8 controls and 6 treated) sedated, intubated, and mechanically ventilated swine, after 5 min of VF, ACLS with vest CPR and periodic defibrillations was performed. Venous blood samples were collected at baseline, after 2 min of CPR, and at 2 and 30 min after return of spontaneous circulation (ROSC). The animals were survived up to 24 hrs and plasma samples were analyzed for glutamate and taurine in 2 controls and 1 animal given peptide. Results: Three of the control animals had ROSC, but none survived for 24 hrs, while 4 of 6 treated animals achieved neurologically intact survival at 24 hrs (p < 0.02). Compared to baseline, both taurine and glutamate plasma concentrations increased in the control group, but the increase was reduced substantially by the peptide treatment at 30 min after ROSC (Figure). Conclusion: The use of the cooling mimicking peptide TAT-PHLPP9c administered during CPR significantly improved 24-hour survival in this swine model of cardiac arrest. It reduced the increase of cerebral and myocardial metabolic biomarkers, which encourages utilizing a strategy of cell-permeable peptides for intravenous administration for more rapid onset of hypothermia-like salutary effects than are possible with current CPR cooling devices.


2014 ◽  
Vol 34 (10) ◽  
pp. e1-e8 ◽  
Author(s):  
Vélvá M Combs ◽  
Heather D Crispell ◽  
Kelly L Drew

Stimulation of N-methyl-D-aspartate receptors (NMDAR) contributes to regenerative neuroplasticity following the initial excitotoxic insult during cerebral ischemia. Stimulation of NMDAR with the partial NMDAR agonist D-cycloserine (DCS) improves outcome and restores hippocampal synaptic plasticity in models of closed head injury. We thus hypothesized that DCS would improve outcome following restoration of spontaneous circulation (ROSC) from cardiac arrest (CA). DCS (10 mg/kg, IP) was administered to Sprague-Dawley rats (male, 250–330 g; 63–84 days old) 24 and 48 hours after 6 or 8 minutes of asphyxial CA. Heart rate and blood pressure declined similarly in all groups. Animals showed neurological deficits after 6 and 8 minutes CA ( P < 0.05, Tukey) and these deficits recovered more quickly after 6 minutes than after 8 minutes of CA. CA decreased the number of healthy neurons within CA1 with no difference between 6 and 8 minutes duration of CA (180.8 ± 27.6 (naïve, n = 5) versus 46.3 ± 33.8 (all CA groups, n = 27) neurons per mm CA1). DCS had no effect on neurological deficits or CA1 hippocampal cell counts ( P > 0.05, Tukey).


2012 ◽  
Vol 117 (1) ◽  
pp. 117-125 ◽  
Author(s):  
Yoshimasa Takeda ◽  
Hiroshi Hashimoto ◽  
Koji Fumoto ◽  
Tetsuya Danura ◽  
Hiromichi Naito ◽  
...  

Background Pharyngeal cooling decreases brain temperature by cooling carotid arteries. This study was designed to evaluate the principle of pharyngeal cooling in monkeys and humans. Methods Monkeys (n = 10) were resuscitated following 12 min of cardiac arrest. Pharyngeal cooling (n = 5), in which cold saline (5°C) was perfused into the cuff at the rate of 500 ml/min, was initiated simultaneously with the onset of resuscitation for 30 min. Patients (n = 3) who were in an intensive care unit were subjected to 30 min of pharyngeal cooling under propofol anesthesia. Results In the animal study, core brain temperature was significantly decreased compared with that in the control group by 1.9°C (SD = 0.8, P &lt; 0.001) and 3.1°C (SD = 1.0, P &lt; 0.001) at 10 min and 30 min after the onset of cooling, respectively. The cooling effect was more evident in an animal with low postresuscitation blood pressure. Total dose of epinephrine, number of direct current shocks, and recovery of blood pressure were not different between the two groups. The pharyngeal epithelium was microscopically intact on day 5. In the clinical study, insertion of the cuff and start of perfusion did not affect heart rate or blood pressure. Tympanic temperature was decreased by 0.6 ± 0.1°C/30 min without affecting bladder temperature. The pharynx was macroscopically intact for 3 days. Conclusions Pharyngeal cooling rapidly and selectively decreased brain temperature in primates and tympanic temperature in humans and did not have adverse effects on return of spontaneous circulation, even when initiated during cardiac arrest in primates.


PLoS ONE ◽  
2021 ◽  
Vol 16 (6) ◽  
pp. e0252875
Author(s):  
Tuo Liang ◽  
Jiarui Chen ◽  
GuoYong Xu ◽  
Zide Zhang ◽  
Jiang Xue ◽  
...  

Objective This study is aimed to develop a new nomogram for the clinical diagnosis of osteoarticular tuberculosis (TB). Methods xCell score estimation to obtained the immune cell type abundance scores. We downloaded the expression profile of GSE83456 from GEO and proceed xCell score estimation. The routine blood examinations of 326 patients were collected for further validation. We analyzed univariate and multivariate logistic regression to identified independent predicted factor for developing the nomogram. The performance of the nomogram was assessed using the receiver operating characteristic (ROC) curves. The correlation of ESR with lymphocytes, monocytes, and ML ratio was performed and visualized in osteoarticular TB patients. Results Compared with the healthy control group in the dataset GSE83456, the xCell score of basophils, monocytes, neutrophils, and platelets was higher, while lymphoid was lower in the EPTB group. The clinical data showed that the cell count of monocytes were much higher, while the cell counts of lymphocytes were lower in the osteoarticular TB group. AUCs of the nomogram was 0.798 for the dataset GSE83456, and 0.737 for the clinical data. We identified the ML ratio, BMI, and ESR as the independent predictive factors for osteoarticular TB diagnosis and constructed a nomogram for the clinical diagnosis of osteoarticular TB. AUCs of this nomogram was 0.843. Conclusions We demonstrated a significant change between the ML ratio of the EPTB and non-TB patients. Moreover, we constructed a nomogram for the clinical diagnosis of the osteoarticular TB diagnosis, which works satisfactorily.


2016 ◽  
Vol 24 (0) ◽  
Author(s):  
Renata Maria de Oliveira Botelho ◽  
Cássia Regina Vancini Campanharo ◽  
Maria Carolina Barbosa Teixeira Lopes ◽  
Meiry Fernanda Pinto Okuno ◽  
Aécio Flávio Teixeira de Góis ◽  
...  

ABSTRACT Objective: to compare the rate of return of spontaneous circulation (ROSC) and death after cardiac arrest, with and without the use of a metronome during cardiopulmonary resuscitation (CPR). Method: case-control study nested in a cohort study including 285 adults who experienced cardiac arrest and received CPR in an emergency service. Data were collected using In-hospital Utstein Style. The control group (n=60) was selected by matching patients considering their neurological condition before cardiac arrest, the immediate cause, initial arrest rhythm, whether epinephrine was used, and the duration of CPR. The case group (n=51) received conventional CPR guided by a metronome set at 110 beats/min. Chi-square and likelihood ratio were used to compare ROSC rates considering p≤0.05. Results: ROSC occurred in 57.7% of the cases, though 92.8% of these patients died in the following 24 hours. No statistically significant difference was found between groups in regard to ROSC (p=0.2017) or the occurrence of death (p=0.8112). Conclusion: the outcomes of patients after cardiac arrest with and without the use of a metronome during CPR were similar and no differences were found between groups in regard to survival rates and ROSC.


2010 ◽  
Vol 2 (1) ◽  
pp. 3 ◽  
Author(s):  
Eric W. Brader ◽  
Dietrich Jehle ◽  
Michael Mineo ◽  
Peter Safar

Prolonged standard cardiopulmonary resuscitation (CPR) does not reliably sustain brain viability during cardiac arrest. Pre-hospital adjuncts to standard CPR are needed in order to improve outcomes. A preliminary dog study demonstrated that surface cooling of the head during arrest and CPR can achieve protective levels of brain hypothermia (30°C) within 10 minutes. We hypothesized that protective head-cooling during cardiac arrest and CPR improves neurological outcomes. Twelve dogs under light ketamine-halothane-nitrous oxide anesthesia were arrested by transthoracic fibrillation. The treated group consisted of six dogs whose shaven heads were moistened with saline and packed in ice immediately after confirmation of ventricular fibrillation. Six control dogs remained at room temperature. All 12 dogs were subjected to four minutes of ventricular fibrillation and 20 minutes of standard CPR. Spontaneous circulation was restored with drugs and countershocks. Intensive care was provided for five hours post-arrest and the animals were observed for 24 hours. In both groups, five of the six dogs had spontaneous circulation restored. After three hours, mean neurological deficit was significantly lower in the treated group (P=0.016, with head-cooled dogs averaging 37% and the normothermic dogs 62%). Two of the six head-cooled dogs survived 24 hours with neurological deficits of 9% and 0%, respectively. None of the control group dogs survived 24 hours. We concluded that head-cooling attenuates brain injury during cardiac arrest with prolonged CPR. We review the literature related to the use of hypothermia following cardiac arrest and discuss some promising approaches for the pre-hospital setting.


2020 ◽  
Vol 79 (Suppl 1) ◽  
pp. 1767.1-1768
Author(s):  
H. Wang ◽  
H. Gao

Background:Gout is an inflammatory disease characterized by hyperuricemia and recurrent arthritis. In severe cases, joint disability and renal insufficiency may occur[1]. In recent years, many studies have found that immune dysfunction plays an important role in the occurrence and development of gout[2]. Therefore, in-depth study of its internal mechanism is of great significance for the prevention and treatment of gout.Objectives:This paper mainly discussed the expression of peripheral blood immune function in patients with gouty arthritis and the changes and significance of peripheral blood immune function in gout with different uric acid levels.Methods:A retrospective analysis was performed on 258 outpatients and inpatients with gout in shanxi medical university from 2016 to 2019, all of which met the diagnostic criteria of the American college of rheumatology (ACR) in 1997, and 41 healthy controls. Complete clinical data and general laboratory data were collected, and peripheral blood lymphocyte and CD4+T cell counts were completed for all subjects.Results:(1) Total peripheral blood B cells of gout patients [238.00 (171.50,323.07) and 191.04 (149.66,253.14), Z=-2.759, P=0.006], Th cells [814.11 (617.50,1052.89) and 625.84 (562.52,750.15), Z=-3.905, P<0.001], Th/Ts [1.4 (1.04,2.00) and 1.11 (0.89,1.52), Z=-2.862,Th17/Treg [0.36 (0.20,0.60) and 0.24 (0.14,0.34), Z=-3.949, P=0.000] and the absolute counts of Th17 cells [9.06 (5.07,15.57) and 7.48 (4.31,10.18), Z=-2.520, P=0.012] were higher than those of the healthy control group, and the differences were statistically significant.The absolute count of Treg cells [28.82 (17.48,38.04) and 30.22 (22.74,39.46), Z=-2.249, P=0.025] was lower than that of the healthy control group, and the difference was statistically significant. (2) The Th17% [1.05 (0.71,1.42) and 1.27 (0.73,2.00), Z=-1.995, P=0.046] and the Th17/Treg [0.25 (0.14,0.44) and 0.39 (0.23,0.63), Z=-3.147, P=0.002] in peripheral blood of patients with high uric acid in the gout group were higher than those in the normal uric acid group, the difference was statistically significant. The Treg % [3.84 (2.65,5.02) and 3.12 (2.36,4.37), Z=-2.239, P=0.025], and the Treg cells [30.75 (21.97,43.27) and 24.07 (16.84,36.29), Z=-2.522, P=0.012] were lower than those in the uric acid control group, with statistically significant differences.Conclusion:The level of Th17 cells in peripheral blood of patients with gout increased significantly while the level of regulatory T cells decreased significantly. Th17 cell level in peripheral blood of the high uric acid group was significantly increased compared with the normal uric acid group, while the regulatory T cell level was also significantly decreased, and the Th17/Treg ratio was also increased. This suggests that regulatory T cells may play an important role in the pathogenesis of gout and are closely related to uric acid metabolism, so the study of internal mechanism can provide a new target for the treatment of gout.References:[1]Ragab G, Elshahaly M, et al. Gout: An old disease in new perspective - A review[J]. Adv Res. 2017;8(5):495–511. DOI: 10.1016/j.jare.2017.04.008.[2]Dai XJ, Tao JH, et al. Changes of Treg/Th17 Ratio in Spleen of Acute Gouty Arthritis Rat Induced by MSU Crystals. [J]. Inflammation. 2018;41(5):1955-1964. Doi: 10.1007/s10753-018-0839-y.Disclosure of Interests:None declared


2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Guangqian Li ◽  
LeiQian ◽  
Pan Gu ◽  
Dan Fan

Abstract Background Neuroprotection strategies after cardiac arrest (CA)/cardiopulmonary resuscitation (CPR) remain key areas of basic and clinical research. This study was designed to investigate the neuroprotective effects of dexmedetomidine following resuscitation and potential mechanisms. Methods Anesthetized rats underwent 6-min asphyxia-based cardiac arrest and resuscitation, after which the experimental group received a single intravenous dose of dexmedetomidine (25 μg/kg). Neurological outcomes and ataxia were assessed after the return of spontaneous circulation. The serum levels and brain expression of inflammation markers was examined, and apoptotic cells were quantified by TUNEL staining. Results Neuroprotection was enhanced by dexmedetomidine post-conditioning after the return of spontaneous circulation. This enhancement was characterized by the promotion of neurological function scores and coordination. In addition, dexmedetomidine post-conditioning attenuated the serum levels of the pro-inflammatory cytokine tumor necrosis factor (TNF)-α at 2 h, as well as interleukin IL-1β at 2, 24, and 48 h. TUNEL staining showed that the number of apoptotic cells in the dexmedetomidine post-conditioning group was significantly reduced compared with the control group. Further western blot analysis indicated that dexmedetomidine markedly reduced the levels of caspase-3 and nuclear factor-kappa B (NF-κB) in the brain. Conclusions Dexmedetomidine post-conditioning had a neuroprotective effect against cerebral injury following asphyxia-induced cardiac arrest. The mechanism was associated with the downregulation of apoptosis and neuroinflammation.


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