Dataset Information

RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation.

ABSTRACT: Cardiac arrest (CA) is the leading cause of death around the world. Survivors after CA and cardiopulmonary resuscitation (CPR) develop moderate to severe cognitive impairment up to 60% at 3 months. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played a pivotal role in ischemic brain injury. This study aimed to identify potential key lncRNAs associated with early cognitive deficits after CA/CPR. LncRNA and mRNA expression profiles of the hippocampus in CA/CPR or sham group were analyzed via high-throughput RNA sequencing, which exhibited 1920 lncRNAs and 1162 mRNAs were differentially expressed. These differentially expressed genes were confirmed to be primarily associated with inflammatory or apoptotic signaling pathways through GO and KEGG pathway enrichment analysis and coding-noncoding co-expression network analysis. Among which, five key pairs of lncRNA-mRNA were further analyzed by qRT-PCR and western blot. We found that the lncRNANONMMUT113601.1 and mRNA Shc1, an inflammation and apoptosis-associated gene, exhibited the most significant changes in hippocampus of CA/CPR mice. Furthermore, we found that the correlations between this lncRNA and mRNA mainly happened in neurons of hippocampus by in situ hybridization. These results suggested that the critical pairs of lncRNA-mRNA may act as essential regulators in early cognitive deficits after resuscitation.

SUBMITTER: Chen C

PROVIDER: S-EPMC7425488 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature

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RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation.

Chen Chan C Liu Changliang C Niu Zhendong Z Li Ming M Zhang Yuhan Y Gao Rui R Chen Hai H Wang Qiao Q Zhang Shu S Zhou Ronghua R Gan Lu L Zhang Zheng Z Zhu Tao T Yu Hai H Liu Jin J

Aging 20200721 14

Cardiac arrest (CA) is the leading cause of death around the world. Survivors after CA and cardiopulmonary resuscitation (CPR) develop moderate to severe cognitive impairment up to 60% at 3 months. Accumulating evidence demonstrated that long non-coding RNAs (lncRNAs) played a pivotal role in ischemic brain injury. This study aimed to identify potential key lncRNAs associated with early cognitive deficits after CA/CPR. LncRNA and mRNA expression profiles of the hippocampus in CA/CPR or sham grou ...[more]

PMID: 32693388

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Project description:To investigate the effects of the combination of extracorporeal cardiopulmonary resuscitation and thrombolytic therapy on the recovery of vital organ function after prolonged cardiac arrest.Laboratory investigation.University laboratory.Pigs.Animals underwent 30-minute untreated ventricular fibrillation cardiac arrest followed by extracorporeal cardiopulmonary resuscitation for 6 hours. Animals were allocated into two experimental groups: t-extracorporeal cardiopulmonary resuscitation (t-ECPR) group, which received streptokinase 1 million units, and control extracorporeal cardiopulmonary resuscitation (c-ECPR), which did not receive streptokinase. In both groups, the resuscitation protocol included the following physiologic targets: mean arterial pressure greater than 70 mm Hg, cerebral perfusion pressure greater than 50 mm Hg, PaO2 150 ± 50 torr (20 ± 7 kPa), PaCO2 40 ± 5 torr (5 ± 1 kPa), and core temperature 33°C ± 1°C. Defibrillation was attempted after 30 minutes of extracorporeal cardiopulmonary resuscitation.A cardiac resuscitability score was assessed on the basis of success of defibrillation, return of spontaneous heart beat, weanability from extracorporeal cardiopulmonary resuscitation, and left ventricular systolic function after weaning. The addition of thrombolytic to extracorporeal cardiopulmonary resuscitation significantly improved cardiac resuscitability (3.7 ± 1.6 in t-ECPR vs 1.0 ± 1.5 in c-ECPR). Arterial lactate clearance was higher in t-ECPR than in c-ECPR (40% ± 15% vs 18% ± 21%). At the end of the experiment, the intracranial pressure was significantly higher in c-ECPR than in t-ECPR. Recovery of brain electrical activity, as assessed by quantitative analysis of electroencephalogram signal, and ischemic neuronal injury on histopathologic examination did not differ between groups. Animals in t-ECPR group did not have increased bleeding complications, including intracerebral hemorrhages.In a porcine model of prolonged cardiac arrest, t-ECPR improved cardiac resuscitability and reduced brain edema, without increasing bleeding complications. However, early electroencephalogram recovery and ischemic neuronal injury were not improved.

Project description:BackgroundVeno-arterial extracorporeal membrane oxygenation has increasingly emerged as a feasible treatment to mitigate the progressive multiorgan dysfunction that occurs during cardiac arrest, in support of further resuscitation efforts.ObjectivesBecause the recent systematic review commissioned in 2018 by the International Liaison Committee on Resuscitation Advanced Life Support task did not include studies without a control group, our objective was to conduct a review incorporating these studies to increase available evidence supporting the use of extracorporeal cardiopulmonary resuscitation (ECPR) for cardiac arrest patients, while waiting for high-quality evidence from randomized controlled trials (RCTs).MethodsMEDLINE, Embase, and Science Citation Index (Web of Science) were searched for eligible studies from database inception to July 20, 2020. The population of interest was adult patients who had suffered cardiac arrest in any setting. We included all cohort studies with 1 exposure/1 group and descriptive studies (ie, case series studies). We excluded RCTs, non-RCTs, and observational analytic studies with a control group. Outcomes included short-term survival and favorable neurological outcome. Short-term outcomes (ie, hospital discharge, 30 days, and 1 month) were combined into a single category.ResultsOur searches of databases and other sources yielded a total of 4302 citations. Sixty-two eligible studies were included (including a combined total of 3638 participants). Six studies were of in-hospital cardiac arrest, 34 studies were of out-of-hospital cardiac arrest, and 22 studies included both in-hospital and out-of-hospital cardiac arrest. Seven hundred and sixty-eight patients of 3352 (23%) had short-term survival; whereas, 602 of 3366 (18%) survived with favorable neurological outcome, defined as a cerebral performance category score of 1 or 2.ConclusionsCurrent clinical evidence is mostly drawn from observational studies, with their potential for confounding selection bias. Although studies without controls cannot supplant case-control or cohort studies, several ECPR studies without a control group show successful resuscitation with impressive results that may provide valuable information to inform a comparison.

Project description:ImportanceFrailty is associated with mortality following surgery and cardiopulmonary resuscitation (CPR) for in-hospital cardiac arrest. Despite the growing focus on frailty as a basis for preoperative risk stratification and concern that CPR in patients with frailty may border on futility, the association between frailty and outcomes following perioperative CPR is unknown.ObjectiveTo determine the association between frailty and outcomes following perioperative CPR.Design, setting, and participantsThis longitudinal cohort study of patients used the American College of Surgeons National Surgical Quality Improvement Program, including more than 700 participating hospitals in the US, from January 1, 2015, through December 31, 2020. Follow-up duration was 30 days. Patients 50 years or older undergoing noncardiac surgery who received CPR on postoperative day 0 were included; patients were excluded if data required to determine frailty, establish outcome, or perform multivariable analyses were missing. Data were analyzed from September 1, 2022, through January 30, 2023.ExposuresFrailty defined as Risk Analysis Index (RAI) of 40 or greater vs less than 40.Outcomes and measuresThirty-day mortality and nonhome discharge.ResultsAmong the 3149 patients included in the analysis, the median age was 71 (IQR, 63-79) years, 1709 (55.9%) were men, and 2117 (69.2%) were White. Mean (SD) RAI was 37.73 (6.18), and 792 patients (25.9%) had an RAI of 40 or greater, of whom 534 (67.4%) died within 30 days of surgery. Multivariable logistic regression adjusting for race, American Society of Anesthesiologists physical status, sepsis, and emergency surgery demonstrated a positive association between frailty and mortality (adjusted odds ratio [AOR], 1.35 [95% CI, 1.11-1.65]; P = .003). Spline regression analysis demonstrated steadily increasing probability of mortality and nonhome discharge with increasing RAI above 37 and 36, respectively. Association between frailty and mortality following CPR varied by procedure urgency (AOR for nonemergent procedures, 1.55 [95% CI, 1.23-1.97]; AOR for emergent procedures, 0.97 [95% CI, 0.68-1.37]; P = .03 for interaction). An RAI of 40 or greater was associated with increased odds of nonhome discharge compared with an RAI of less than 40 (AOR, 1.85 [95% CI, 1.31-2.62]; P < .001).Conclusions and relevanceThe findings of this cohort study suggest that although roughly 1 in 3 patients with an RAI of 40 or greater survived at least 30 days following perioperative CPR, higher frailty burden was associated with increased mortality and greater risk of nonhome discharge among survivors. Identifying patients who are undergoing surgery and have frailty may inform primary prevention strategies, guide shared decision-making regarding perioperative CPR, and promote goal-concordant surgical care.

Project description:BACKGROUND:The prognosis in refractory out-of-hospital cardiac arrest (OHCA) with ongoing cardiopulmonary resuscitation (CPR) at hospital arrival is often considered dismal. The use of extracorporeal cardiopulmonary resuscitation (eCPR) for perfusion enhancement during resuscitation has shown variable results. We aimed to investigate outcome in refractory OHCA patients managed conservatively without use of eCPR. METHODS:We included consecutive OHCA patients with refractory arrest or prehospital return of spontaneous circulation (ROSC) in the Copenhagen area in 2002-2011. RESULTS:A total of 3992 OHCA patients with resuscitation attempts were included; in 2599, treatment was terminated prehospital, and 1393 (35%) were brought to the hospital either with ROSC (n?=?1285, 92%) or with refractory OHCA (n?=?108, 8%). Of patients brought in with refractory OHCA, 56 (52%) achieved ROSC in the emergency department. There were no differences between patients with refractory OHCA or prehospital ROSC with regard to age, sex, comorbidities, or etiology of OHCA. Time to emergency medical services (EMS) arrival was similar, whereas time to ROSC (when ROSC was achieved) was longer in refractory OHCA patients (EMS, 6 (5-9] vs. 7 [5-10] min, p?=?0.8; ROSC, 15 [9-22] vs. 27 [20-41] min, p?<?0.001). Independent factors associated with transport with refractory OHCA instead of prehospital termination of therapy were OHCA in public (OR, 3.6 [95% CI, 2.2-5.8]; p?<?0.001), witnessed OHCA (OR, 3.7 [2.0-7.1]; p?<?0.001), shockable rhythm (OR, 3.0 [1.9-4.7]; p?<?0.001), younger age (OR, 1.2 [1.1-1.2]; p?<?0.001), and later calendar year (OR, 1.4 [1.2-1.6]; p?<?0.001). Thirty-day survival was 20% in patients with refractory OHCA compared with 42% in patients with prehospital ROSC (p?<?0.001). Four of 28 refractory OHCA patients with duration of resuscitation >?60 min achieved ROSC. No difference in favorable neurological outcome in patients surviving to discharge was found (prehospital ROSC 84% vs. refractory OHCA 86%; p?=?0.7). CONCLUSIONS:Survival after refractory OHCA with ongoing CPR at hospital arrival was significantly lower than among patients with prehospital ROSC. Despite a lower survival, the majority of survivors with both refractory OHCA and prehospital ROSC were discharged with a similar degree of favorable neurological outcome, indicating that continued efforts in spite of refractory OHCA are not in vain and may still lead to favorable outcome even without eCPR.

Dataset Information

RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation.

Publications

RNA-seq analysis of the key long noncoding RNAs and mRNAs related to cognitive impairment after cardiac arrest and cardiopulmonary resuscitation.

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