Post-cardiac Arrest Syndrome Research Articles

Suppression of PCK1 attenuates neuronal injury and improves post-resuscitation outcomes.

Cardiac arrest (CA) is a critical medical emergency that can occur in both patients with preexisting conditions and otherwise healthy individuals. Despite successful resuscitation through cardiopulmonary resuscitation (CPR), many survivors are at significant risk of developing post-cardiac arrest syndrome (PCAS), a complex systemic response to CA that includes brain injury as a major component. Phosphoenolpyruvate carboxykinase 1 (PCK1), the first rate-limiting enzyme in gluconeogenesis, has been implicated in various diseases. However, its role in neuronal damage following CA/CPR remains unclear. To investigate the role of PCK1 in neuronal damage after CA/CPR, we established the CA/CPR animal model and hypoxia/re‑oxygenation (H/R) cell model, manipulated PCK1 expression both in vivo and in vitro. We found increased expression of PCK1 in cortical neurons after CA/CPR. In vivo PCK1 overexpression exacerbated brain injury after CA/CPR via augmenting neuroinflammation and neuronal apoptosis. RNA-sequencing suggested PCK1-OE disturbed the neuronal metabolism while immunoprecipitation/mass spectrometry (IP/MS) revealed that PCK1 contributed to the mitochondrial dysfunction via binding to Voltage-dependent anion-selective channel 1 (VDAC1) and promoting its oligomerization and cytochrome c release. Besides, we confirmed that 3-Mercaptopicolinic acid (3-MPA), the PCK1 inhibitor, could ameliorate the mitochondrial dysfunction and apoptosis of neurons both in vitro and in vivo. For the first time, we identified the detrimental role of PCK1 in post-CA brain injury. During CA/CPR, excessive PCK1 binds to VDAC1, promoting its oligomerization and cytochrome c release which leading to neuronal apoptosis and eventually PCAS. Utilization of 3-MPA during CPR could effectively improve the survival rate and prognosis of mice after CA, which may provide a novel strategy for CA/CPR treatment.

Bundling Care in Comatose Post Cardiac Arrest Patients

Post cardiac arrest syndrome (PCAS), an inflammatory state resulting from an ischemia-reperfusion injury impacting multiple organ systems. Hospital teams from the ED to Cath Labs to the ICU must practice in synchrony to optimize care. Key priorities in patients who remain comatose following return of spontaneous circulation are imperative to reduce the impact of PCAS. The team must focus on interventions and coordinated care to limit the damage of reperfusion injury to the brain/body. The complexity and heterogeneity of this patient population presents the team with challenges related to time, place, intervention sequence and elements. This presentation will focus on delivering care to the cardiac arrest and comatose post-cardiac arrest patient, selecting interventions maximizing oxygenation/ventilation and hemodynamics while implementing the strategies of TTM, Neurologic care, seizure surveillance, and management to lessen the pathologic impact of PCAS in the form of bundles of care. Target goals, interventions, and outcomes for the bundle elements will be shared.

Ventilator-Associated Pneumonia After Cardiac Arrest and Prevention Strategies: A Narrative Review.

Background and Objectives: Ventilator-associated pneumonia (VAP) poses a significant threat to the clinical outcomes and hospital stays of mechanically ventilated patients, particularly those recovering from cardiac arrest. Given the already elevated mortality rates in cardiac arrest cases, the addition of VAP further diminishes the chances of survival. Consequently, a paramount focus on VAP prevention becomes imperative. This review endeavors to comprehensively delve into the nuances of VAP, specifically in patients requiring mechanical ventilation in post-cardiac arrest care. The overarching objectives encompass (I) exploring the etiology, risk factors, and pathophysiology of VAP, (II) delving into available diagnostic modalities, and (III) providing insights into the management options and recent treatment guidelines. Methods: A literature search was conducted using PubMed, MEDLINE, and Google Scholar databases for articles about VAP and Cardiac arrest. We used the MeSH terms "VAP", "Cardiac arrest", "postcardiac arrest syndrome", and "postcardiac arrest syndrome". The clinical presentation, diagnostic, and management strategies of VAP were summarized, and all authors reviewed the selection and decided which studies to include. Key Content and Findings: The incidence and mortality rates of VAP exhibit significant variability, yet a recurring pattern emerges, marked by prolonged hospitalization and exacerbated clinical outcomes. This pattern is attributed to the elevated incidence of drug-resistant infections and the delayed initiation of antimicrobial treatment. This review focuses on VAP, aiming to offer valuable insights into the efficient identification and management of this fatal complication in post-cardiac arrest patients. Conclusion: The prognosis for survival after cardiac arrest is already challenging, and the outlook becomes even more daunting when complicated by VAP. The timely diagnosis of VAP and initiation of antibiotics pose considerable challenges, primarily due to the invasive nature of obtaining high-quality samples and the time required for speciation and identification of antimicrobial sensitivity. The controversy surrounding prophylactic antibiotics persists, but promising new strategies have been proposed; however, they are still awaiting well-designed clinical trials.

Chinese clinical practice consensus for device-supported treatment in adults with post-cardiac arrest syndrome (2024 Edition)

Chinese clinical practice consensus for device-supported treatment in adults with post-cardiac arrest syndrome (2024 Edition)

Effect Size of Targeted Temperature Management in Pediatric Patients with Post-Cardiac Arrest Syndrome According to the Severity.

Few studies have investigated the differential effects of targeted temperature management (TTM) according to the severity of the condition in pediatric patients with post-cardiac arrest syndrome (PCAS). This study was aimed at evaluating the differential effects of TTM in pediatric patients with PCAS according to a risk classification tool developed by us, the rCAST. We used data from a nationwide prospective registry for out-of-hospital cardiac arrest (OHCA) patients in Japan. We classified eligible pediatric PCAS patients (aged ≤ 18 years) into quintiles based on their rCAST scores and evaluated the effect of TTM on the neurological outcomes in each severity group. Then, focusing on the severity group that appeared to benefit from TTM, we also evaluated the effect of TTM by propensity score analysis. Good neurological outcome was defined as a score on the Cerebral Performance Category or Pediatric Cerebral Performance Category scale of ≤2 at 30 days. Among 1526 OHCA pediatric patients enrolled in the registry, the data of 307 PCAS patients were analyzed. None of the patients in the fifth quintile (rCAST ≥ 18.5) showed a good neurological outcome, regardless of whether they received TTM or not (0% [0/20] vs. 0% [0/73]). The propensity score analysis showed that TTM was significantly associated with a good neurological outcome in patients with rCAST scores in the first to fourth quintile (odds ratio: 1.21 [1.04-1.40], p = 0.014). TTM was significantly associated with good neurological outcomes in pediatric PCAS patients with rCAST scores of ≤18.0.

Post-resuscitation care in the NICU

Post-cardiac arrest syndrome is a unique pathophysiologic condition that is well-described in adult and pediatric populations. Early, goal-directed care after cardiac arrest can mitigate ongoing injury, improve clinical outcomes, and prevent re-arrest. There is a paucity of evidence about post-cardiac arrest care in the NICU, however, pediatric principles and guidelines can be applied in the NICU in the appropriate clinical context.

Prognostic value of gray–white matter ratio measured by brain MRI-based CT structures in comatose patients after cardiac arrest

BackgroundPost-cardiac arrest care advancements have improved resuscitation outcomes, but many survivors still face severe neurological deficits or death from brain injury. Herein, we propose a consistent prognosis prediction approach using magnetic resonance imaging (MRI) to analyze anatomical regions represented by the gray and white matter, and subsequently apply it on computed tomography (CT) to calculate the gray–white matter ratio (GWR). We compared this novel method with traditional measures to validate its ability to predict the prognosis of patients resuscitated after cardiac arrest. MethodsConducted retrospectively at two South Korean tertiary university hospitals from January 2018 to December 2022, the study included adult cardiac arrest survivors treated with therapeutic target temperature management. Patients underwent brain CT within 2 h and brain MRI within 3 days of return of spontaneous circulation. The outcome was the neurological status at discharge. Statistical analyses included receiver operating characteristic curve analysis and determining cutoff values to predict poor neurological outcomes. ResultsOverall, 51 of the 421 adult comatose cardiac arrest survivors examined met the inclusion criteria. Among these, 33 and 18 exhibited good and poor neurological outcomes, respectively. Demographic and cardiac arrest characteristics were compared between the two groups, revealing significant differences. Analyses of gray and white matter attenuation and GWR measurements highlighted significant differences between the good and poor outcome groups. ConclusionOur study introduces a novel method for measuring GWR using MRI-based brain CT, demonstrating superior prognostic accuracy in predicting neurological outcomes in patients with post-cardiac arrest syndrome compared to traditional methods.

Opportunities and Challenges of Application of Cytosorb Therapy in Sepsis Management

Sepsis is a life-threatening organ dysfunction due to a dysregulated host response to infection. In 2017, an estimated 48·9 million incident cases of sepsis were recorded worldwide, and 11·0 million sepsis-related deaths were reported, representing 19·7% of all global deaths.1 Though overall data related to sepsis is poor but it is also a major health care challenge for resource limited countries. Severe sepsis is a significant & common health problem in ICU patients of Bangladesh2. A continuum of severity from sepsis to septic shock and multi-organ dysfunction syndrome (MODS) exists. MODS is a clinical syndrome characterized by the development of progressive and potentially reversible physiologic dysfunction in 2 or more organs or organ systems that is induced by a variety of acute insults, including sepsis. Sepsis leads to malignant intravascular inflammation, coagulopathy, circulatory derangement, tissue hypoxia, cytotoxicity and apoptosis. As a result, dysfunction of vital organ systems occur. Host response and other factors influenc outcome. Patients with sepsis must be treated with-timely, appropriate antibiotics, intravenousfluids, vasopressor and inotropic support & oxygen therapy.3 Other additional treatments including extracorporeal blood purification techniques (BPT). These techniques include hemofiltration, hemoperfusion, intermittent or continuous high-volume hemofiltration (HVHF), plasmapheresis or adsorption.4 The rationale behind such an approach is to achieve “immune homeostasis” which theoretically reduces the potential damage caused by dysregulation of the host response to infection. Given the pivotal role of cytokine production in sepsis, it follows that removal of these substances, through such BPT, may attenuate the response particularly in the early phase of sepsis.5 Indications include 1) Rhabdomyolysis resulting from Reperfusion syndrome, Trauma, Malignant Hyperthermia. 2) External injuries including Sepsis/Septic shock, Hemorrhagic shock, Trauma, Ruptured aortic aneurysm, Post-Cardiac Arrest Syndrome, Cardio-pulmonary resuscitation, Extensive surgery, Organ transplantation, Cardiosurgical intervention, Severe skin and soft tissue damage, Burns, Necrotizing fasciitis, Post-Cardiotomy Syndrome, Acute Respiratory Distress Syndrome. 3) Diseases: Pancreatitis, Liver insufficiency, Renal insufficiency, Stroke, Myocardial infarction, Cardiogenic shock/Heart failure, Tumor Lysis Syndrome, Hemophagocytosis Syndrome. Liver failure/Hyperbilirubinemia bridging to transplant or to recovery, Life-threatening bleeding under Direct Oral Anticoagulants (DOAC)6. Bangladesh Crit Care J September 2024; 12 (2): 79-80

Prediction of poor prognosis using the peak systolic velocity and early diastolic velocity of the central retinal artery in patients with post‐cardiac arrest syndrome

AbstractIntroductionMonitoring intracranial pressure (ICP) in patients with post‐cardiac arrest syndrome (PCAS) is crucial for effective management and prognosis assessment. However, continuous ICP monitoring is rarely practiced. Increased ICP is often associated with the impairment of brain autoregulation. This study investigated whether central retinal artery (CRA) flow velocity, autoregulation status according to mean arterial pressure (MAP), and the optic nerve sheath diameter (ONSD)/eyeball transverse diameter (ETD) ratio could predict poor prognosis related to increased ICP in PCAS patients.MethodsIn this multicenter prospective observational study, transocular ultrasonography of the optic nerve sheath was performed on 38 PCAS patients treated with targeted temperature management from December 2021 to November 2022. CRA peak systolic velocity (PSV), early diastolic velocity (eDV), MAP, CRA‐PSV changes following MAP changes (autoregulation), and ONSD/ETD ratio were measured repeatedly from days 0 to 4 post‐admission.ResultsUnivariable analysis indicated that CRA‐PSV, nonpositive or flat CRA‐eDV, and disrupted autoregulation correlated with a poor prognosis (Cerebral Performance Category 4 or 5). In multivariable analysis, nonpositive CRA‐eDV or disrupted autoregulation was the most significant predictor of poor prognosis (odds ratio, 40.576; p = 0.002), with an area under the curve of 0.774. The ONSD/ETD ratio did not show a significant correlation.ConclusionsNonpositive CRA‐eDV, CRA‐PSV and disrupted autoregulation can predict poor prognosis in PCAS patients. Transocular Doppler ultrasonography of the CRA and autoregulation assessment may aid in ICP monitoring and management in PCAS patients.

Hydrogen therapy from the initiation to its practical applications

Molecular hydrogen (H2) has emerged as a therapeutic and prophylactic agent devoid of adverse effects. H2 demonstrates multifaceted functionality across diverse cell types and organs, attributable to its interaction with oxidized hemes as a fundamental molecular mechanism. Given the abundance of various heme types both intracellularly and extracellularly, the broad-ranging effects of H2 are comprehensible. Subsequent Pathways are mediated by end-or modified- products of lipid peroxide followed by free radical chain reactions. Notably, H2 confers benefits not only to patients afflicted with diseases but also to individuals seeking to enhance health and wellness. The mission of hydrogen medicine encompasses addressing unresolved medical challenges, including cerebral infarction, post-cardiac arrest syndrome, advanced cancer, metabolic syndrome, and dementia. Transitioning from animal experiments to clinical studies is imperative to confront these formidable diseases effectively.

Cardiac arrest and microcirculatory dysfunction: a narrative review.

This review provides an overview of the role of microcirculation in cardiac arrest and postcardiac arrest syndrome through handheld intravital microscopy and biomarkers. It highlights the importance of microcirculatory dysfunction in postcardiac arrest outcomes and explores potential therapeutic targets. Sublingual microcirculation is impaired in the early stage of postarrest and is potentially associated with increased mortality. Recent work suggests that the proportion of perfused small vessels is predictive of mortality. Microcirculatory impairment is consistently found to be independent of macrohemodynamic parameters. Biomarkers of endothelial cell injury and endothelial glycocalyx degradation are elevated in postarrest settings and may predict mortality and clinical outcomes, warranting further studies. Recent studies of exploratory therapies targeting microcirculation have shown some promise in animal models but still require significant research. Although research continues to suggest the important role that microcirculation may play in postcardiac arrest syndrome and cardiac arrest outcomes, the existing studies are still limited to draw any definitive conclusions. Further research is needed to better understand microcirculatory changes and their significance to improve cardiac arrest care and outcomes.

Optimal Targeted Temperature Management for Patients with Post-Cardiac Arrest Syndrome.

Background: To prevent hypoxic-ischemic brain damage in patients with post-cardiac arrest syndrome (PCAS), international guidelines have emphasized performing targeted temperature management (TTM). However, the most optimal targeted core temperature and cooling duration reached no consensus to date. This study aimed to clarify the optimal targeted core temperature and cooling duration, selected according to the time interval from collapse to return of spontaneous circulation (ROSC) in patients with PCAS due to cardiac etiology. Methods: Between 2014 and 2020, the targeted core temperature was 34 °C or 35 °C, and the cooling duration was 24 h. If the time interval from collapse to ROSC was within 20 min, we performed the 35 °C targeted core temperature (Group A), and, if not, we performed the 34 °C targeted core temperature (Group B). Between 2009 and 2013, the targeted core temperature was 34 °C, and the cooling duration was 24 or 48 h. If the interval was within 20 min, we performed the 24 h cooling duration (Group C), and, if not, we performed the 48 h cooling duration (Group D). Results: The favorable neurological outcome rates at 30 days following cardiac arrest were 45.7% and 45.5% in Groups A + B and C + D, respectively (p = 0.977). In patients with ROSC within 20 min, the favorable neurological outcome rates at 30 days following cardiac arrest were 75.6% and 86.4% in Groups A and C, respectively (p = 0.315). In patients with ROSC ≥ 21 min, the favorable neurological outcome rates at 30 days following cardiac arrest were 29.3% and 18.2% in Groups B and D, respectively (p = 0.233). Conclusions: Selecting the optimal target core temperature and the cooling duration for TTM, according to the time interval from collapse to ROSC, may be helpful in patients with PCAS due to cardiac etiology.

Echocardiography in Cardiac Arrest: Incremental Diagnostic and Prognostic Role during Resuscitation Care.

Cardiac arrest (CA) is a life-critical condition. Patients who survive after CA go into a defined post-cardiac arrest syndrome (PCAS). In this clinical context, the role of the echocardiogram in recent years has become increasingly important to assess the causes of arrest, the prognosis, and any direct and indirect complications dependent on cardiopulmonary resuscitation (CPR) maneu-vers. We have conduct a narrative revision of literature. The aim of our review is to evaluate the increasingly important role of the transthoracic and transesophageal echocardiogram in the CA phase and especially post-arrest, analyzing the data already present in the literature. Transthoracic and transesophageal echocardiogram in the CA phase take on important diagnostic and prognostic role.

Monitoring of Cerebral Blood Flow Autoregulation after Cardiac Arrest.

Background: Cardiac arrest remains one of the leading causes of death. After successful resuscitation of patients in cardiac arrest, post-cardiac arrest syndrome develops, part of it being an impaired cerebral blood flow autoregulation. Monitoring cerebral blood flow autoregulation after cardiac arrest is important for optimizing patient care and prognosticating patients' survival, yet remains a challenge. There are still gaps in clinical implications and everyday use. In this article, we present a systematic review of studies with different methods of monitoring cerebral blood flow autoregulation after non-traumatic cardiac arrest. Methods: A comprehensive literature search was performed from 1 June 2024 to 27 June 2024 by using multiple databases: PubMed, Web of Science, and the Cochrane Central Register of Controlled Trials. Inclusion criteria were studies with an included description of the measurement of cerebral blood flow autoregulation in adult patients after non-traumatic cardiac arrest. Results: A total of 16 studies met inclusion criteria. Our data show that the most used methods in the reviewed studies were near-infrared spectroscopy and transcranial Doppler. The most used mathematical methods for calculating cerebral autoregulation were cerebral oximetry index, tissue oxygenation reactivity index, and mean flow index. Conclusions: The use of various monitoring and mathematical methods for calculating cerebral blood flow autoregulation poses a challenge for standardization, validation, and daily use in clinical practice. In the future studies, focus should be considered on clinical validation and transitioning autoregulation monitoring techniques to everyday clinical practice, which could improve the survival outcomes of patients after cardiac arrest.

Simultaneous prognostic score validation in patients with out-of-hospital cardiac arrest by a post-hoc analysis based on national multicenter registry

Using a nationwide multicenter prospective registry in Japan’s data, we calculated prognostic and predictive scores, including the Out-of-Hospital Cardiac Arrest (OHCA); Cardiac Arrest Hospital Prognosis (CAHP); Nonshockable rhythm, Unwitnessed arrest, Long no-flow or Long low-flow period, blood PH < 7.2, Lactate > 7.0 mmol/L, End-stage chronic kidney disease on dialysis, Age ≥ 85 years, Still resuscitation, and Extracardiac cause (NULL-PLEASE); revised post-Cardiac Arrest Syndrome for Therapeutic hypothermia (rCAST); and MIRACLE2 scores, for adult patients with cardiac arrest. The MIRACLE2 score was validated with the modified MIRACLE2 score, which excludes information of pupillary reflexes. Each score was calculated only for the cases with no missing data for the variables used. These scores’ accuracies were compared using neurological outcomes 30 days after out-of-hospital cardiac arrest (OOHCA). Patients with a cerebral performance category scale of 1 or 2 were designated as having favorable neurological outcomes. Each score’s discrimination ability was evaluated by the receiver operating characteristic curve’s area under the curve (AUC). To assess in detail in areas of high specificity and high sensitivity, which are areas of interest to clinicians, partial AUCs were also used. The analysis included 11,924 hospitalized adult patients. The AUCs of the OHCA, MIRACLE2, CAHP, rCAST, and NULL-PLEASE scores for favorable neurological outcomes were 0.713, 0.727, 0.785, 0.761, and 0.831, respectively. The CAHP and NULL-PLEASE scores were significantly more accurate than the rest. Accuracies did not differ significantly between the CAHP and NULL-PLEASE scores. The NULL-PLEASE score was significantly better at discriminating favorable neurological prognoses at 30 days in patients with OOHCA compared to other scoring systems.

Abstract Tu002: Mesenchymal Stem Cell-Derived Extracellular Vesicles Mitigate Mitochondrial DNA-Induced Activation of Porcine Peripheral Blood Mononuclear Cells

Objective: Systemic inflammation is a well-established component of post-cardiac arrest syndrome (PCAS), a condition responsible for significant morbidity and mortality in patients that are initially resuscitated from sudden cardiac arrest. Immune cell activation is pivotal in PCAS pathophysiology, with emerging evidence implicating mitochondrial DNA (mtDNA) as a potent pro-inflammatory stimulus in this context. Given the paucity of available interventions to inhibit mtDNA-induced immune cell activation, we investigated the therapeutic potential of mesenchymal stem cell-derived extracellular vesicles (MSC-EVs) to modulate the inflammatory response of porcine peripheral blood mononuclear cells (PBMCs) activated by mtDNA in vitro . Methods: Porcine bone marrow-derived mesenchymal stem cells (MSCs; P2) were cultured for 5 days and serum-starved for 3 days to collect MSC-EVs. These EVs were isolated from conditioned media (CM) using size exclusion chromatography and ultracentrifugation, then characterized by nanoparticle tracking analysis (ZetaView) and ExoCheck. Naïve PBMCs from healthy swine were cultured for 1 week before stimulation with lipofectamine 2000 (TR-control) or 2 µg/mL mtDNA+TR. MSC-EVs were added to activated PBMCs (2.5e8–2e9 EVs/well) and inflammatory surface marker expression (flow cytometry), inflammatory cytokine transcripts (qPCR) and release (ELISA), and reactive oxygen/nitrogen species (ROS/RNS) production were assessed 24 hours later. Results: mtDNA-stimulated PBMC populations exhibited altered surface marker expression consistent with enrichment of inflammatory granulocytes (CD172+CD163-), macrophages (CD14+CD163+), and adhesion molecules (CD172+) compared to TR-control (all p&lt;0.05). Addition of MSC-EVs significantly reduced the number of all inflammatory cell populations, with the most prominent effects achieved at the highest EV dose (2e9 EVs/well). Likewise, MSC-EVs significantly attenuated mtDNA-activated PBMC expression and secretion of TNFα, IL-1β, and IL-6 ( Figure) and decreased ROS/RNS production in a dose-dependent manner. Conclusion: MSC-EVs attenuate mtDNA-induced activation of PBMCs in a dose-dependent manner, as determined by reductions in pro-inflammatory surface marker expression, inflammatory cytokine gene expression and secretion, and ROS/RNS production. These findings indicate that MSC-EVs may be a viable therapeutic for the inhibition of mtDNA-mediated immune activation in PCAS.

Differential Mitochondrial Bioenergetics in Neurons and Astrocytes Following Ischemia-Reperfusion Injury and Hypothermia.

The close interaction between neurons and astrocytes has been extensively studied. However, the specific behavior of these cells after ischemia-reperfusion injury and hypothermia remains poorly characterized. A growing body of evidence suggests that mitochondria function and putative transference between neurons and astrocytes may play a fundamental role in adaptive and homeostatic responses after systemic insults such as cardiac arrest, which highlights the importance of a better understanding of how neurons and astrocytes behave individually in these settings. Brain injury is one of the most important challenges in post-cardiac arrest syndrome, and therapeutic hypothermia remains the single, gold standard treatment for neuroprotection after cardiac arrest. In our study, we modeled ischemia-reperfusion injury by using in vitro enhanced oxygen-glucose deprivation and reperfusion (eOGD-R) and subsequent hypothermia (HPT) (31.5 °C) to cell lines of neurons (HT-22) and astrocytes (C8-D1A) with/without hypothermia. Using cell lysis (LDH; lactate dehydrogenase) as a measure of membrane integrity and cell viability, we found that neurons were more susceptible to eOGD-R when compared with astrocytes. However, they benefited significantly from HPT, while the HPT effect after eOGD-R on astrocytes was negligible. Similarly, eOGD-R caused a more significant reduction in adenosine triphosphate (ATP) in neurons than astrocytes, and the ATP-enhancing effects from HPT were more prominent in neurons than astrocytes. In both neurons and astrocytes, measurement of reactive oxygen species (ROS) revealed higher ROS output following eOGD-R, with a non-significant trend of differential reduction observed in neurons. HPT after eOGD-R effectively downregulated ROS in both cells; however, the effect was significantly more effective in neurons. Lipid peroxidation was higher after eOGD-R in neurons, while in astrocytes, the increase was not statistically significant. Interestingly, HPT had similar effects on the reduction in lipoperoxidation after eOGD-R with both types of cells. While glutathione (GSH) levels were downregulated after eOGD-R in both cells, HPT enhanced GSH in astrocytes, but worsened GSH in neurons. In conclusion, neuron and astrocyte cultures respond differently to eOGD-R and eOGD-R + HTP treatments. Neurons showed higher sensitivity to ischemia-reperfusion insults than astrocytes; however, they benefited more from HPT therapy. These data suggest that given the differential effects from HPT in neurons and astrocytes, future therapeutic developments could potentially enhance HPT outcomes by means of neuronal and astrocytic targeted therapies.

Inflammatory response after prehospital high-dose glucocorticoid to patients resuscitated from out-of-hospital cardiac arrest: A sub-study of the STEROHCA trial

BackgroundThe post-cardiac arrest syndrome (PCAS) after out-of-hospital cardiac arrest (OHCA) is characterized by a series of pathological events, including inflammation. In the randomized “STERoid for OHCA” (STEROHCA) trial, prehospital high-dose glucocorticoid decreased interleukin (IL) 6 and C-reactive protein levels following resuscitated OHCA. The aim of this predefined sub-study was to assess the inflammatory response the first three days of admission. MethodsThe STEROHCA trial enrolled 137 OHCA patients randomized to either a single prehospital injection of methylprednisolone 250 mg or placebo. Inflammatory markers, including pro- and anti-inflammatory cytokines, were analyzed in plasma samples, from 0-, 24-, 48-, and 72 h post-admission. Mixed-model analyses were applied using log-transformed data to assess group differences. ResultsThe 137 patients included in this sub-study had a median age of 67 years (57 to 74), and the 180-day survival rates were 75% (n = 51/68) and 64% (n = 44/69) in the glucocorticoid and placebo group, respectively. A total of 130 (95%) patients had at least one plasma sample available. The anti-inflammatory cytokine IL-10 was increased at hospital admission in the glucocorticoid group (ratio 2.74 (1.49–5.05), p = 0.006), but the intervention showed the strongest effect after 24 h, decreasing pro-inflammatory levels of IL-6 (ratio 0.06 (0.03–0.10), p < 0.001), IL-8 (ratio 0.53 (0.38–0.75), p < 0.001), macrophage chemokine protein-1 (MCP-1, ratio 0.02 (0.13–0.31), p < 0.001), macrophage inflammatory protein-1-beta (MIP-1b, ratio 0.28 (0.18–0.45), p < 0.001), and tumor necrosis factor-α (TNF-α, ratio 0.6 (0.4–0.8), p = 0.01). ConclusionAdministering high-dose glucocorticoid treatment promptly after resuscitation from OHCA influenced the inflammatory response with a reduction in several systemic proinflammatory cytokines after 24 h. Trial registrationEudraCT number: 2020–000855-11; submitted March 30, 2020.URL: https://www.clinicaltrials.gov; Unique Identifier: NCT04624776.

Checkpoint for Considering Interleukin-6 as a Potential Target to Mitigate Secondary Brain Injury after Cardiac Arrest.

Interleukin-6 (IL-6) was suggested as a potential target for intervention to mitigate brain injury. However, its neuro-protective effect in post-resuscitation care has not been proven. We investigated the time-course of changes in IL-6 and its association with other markers (systemic inflammation and myocardial and neuronal injury), according to the injury severity of the cardiac arrest. This retrospective study analyzed IL-6 and other markers at baseline and 24, 48, and 72 h after the return of spontaneous circulation. The primary outcome was the association of IL-6 with injury severity as assessed using the revised Post-Cardiac Arrest Syndrome for Therapeutic Hypothermia scoring system (low, moderate, and high severity). Of 111 patients, 22 (19.8%), 61 (55.0%), and 28 (25.2%) had low-, moderate-, and high-severity scores, respectively. IL-6 levels were significantly lower in the low-severity group than in the moderate- and high-severity groups at baseline and at 24 h and 72 h (p < 0.005). While IL-6 was not independently associated with neuronal injury markers in the low-severity group, it was demonstrated to be associated with it in the moderate-severity (β [95% CI] = 4.3 [0.1-8.6], R2 = 0.11) and high-severity (β [95% CI] = 7.9 [3.4-12.5], R2 = 0.14) groups. IL-6 exhibits distinct patterns across severity and shows differential associations with systemic inflammation or neuronal injury.

Circulating glycocalyx shedding products as biomarkers for evaluating prognosis of patients with out-of-hospital cardiac arrest after return of spontaneous circulation

The endothelial glycocalyx is damaged in postcardiac arrest syndrome (PCAS), but the prognostic value is unknown. We aimed to observe the expression and prognostic value of glycocalyx shedding products, including syndecan-1 (SDC-1), hyaluronan (HA), and heparan sulfate (HS) in PCAS. Data on clinical and 28-day outcomes of seventy-one consecutive patients with out-of-hospital cardiac arrest (OHCA) after the return of spontaneous circulation (ROSC) were collected. SDC-1, HA, and HS were measured on days 0, 1, and 3 after ROSC. Thirty healthy individuals were controls. Glycocalyx shedding was observed in human umbilical vein endothelial cells (HUVECs) stimulated during hypoxia and reoxygenation in vitro. Within 4 h of ROSC, SDC-1 and HA levels, significantly increased. In the 28-day non-survivors, HA levels showed a gradual upward trend, SDC-1 remained at a high level, and HS levels first increased, then decreased. Kaplan–Meier curves and binary logistic regression analysis showed the prognostic value of SDC-1 levels on days 0, 1, and 3, HA levels on days 1 and 3, and HS levels on day 1. Only HS levels on day 1 showed a prognostic value for 28-day neurological outcomes. SDC-1 and HA levels were positively correlated with the no-flow time. In vitro, HUVECs showed shedding of SDC-1 and HS during a prolonged duration of hypoxia. After ROSC, SDC-1, HA, and HS levels may predict the 28-day survival after PCAS, and HS levels are associated with functional outcomes.