Transcription factor EB (TFEB) improves ventricular remodeling after myocardial infarction by inhibiting Wnt/ß-catenin signaling pathway.

Background: Adverse left ventricular remodeling after myocardial infarction (MI) compromises cardiac function and increases heart failure risk. Until now, comprehension of the role transcription factor EB (TFEB) plays after MI is limited. Objectives: The purpose of this study was to describe the effects of TFEB on fibroblasts differentiation and extracellular matrix expression after MI. Methods: AAV9 (adeno-associated virus) mediated up- and down-regulated TFEB expressions were generated in C57BL/6 mice two weeks before the MI modeling. Echocardiography, Masson, Sirius red staining immunofluorescence, and wheat germ agglutinin staining were performed at 3 days, and 1, 2, and 4 weeks after MI modeling. Fibroblasts collected from SD neonatal rats were transfected by adenovirus and siRNA, and cell counting kit-8 (CCK8), immunofluorescence, wound healing and Transwell assay were conducted. Myocardial fibrosis-related proteins were identified by Western blot. PNU-74654 (100 ng/mL) was used for 12 hours to inhibit ß-catenin-TCF/LEF1 complex. Results: The up-regulation of TFEB resulted in reduced fibroblasts proliferation and its differentiation into myofibroblasts in vitro studies. A significant up-regulation of EF and down-regulation of myocyte area was shown in the AAV9-TFEB group. Meanwhile, decreased protein level of α-SMA and collagen I were observed in vitro study. TFEB didn't affect the concentration of ß-catenin. Inhibition of TFEB, which promoted cell migration, proliferation and collagen I expression, was counteracted by PNU-74654. Conclusions: TFEB demonstrated potential in restraining fibrosis after MI by inhibiting the Wnt/ß-catenin signaling pathway.

Identification of Potential Biomarkers of Septic Shock Based on Pathway and Transcriptome Analyses of Immune-Related Genes.

Immunoregulation is crucial to septic shock (SS) but has not been clearly explained. Our aim was to explore potential biomarkers for SS by pathway and transcriptional analyses of immune-related genes to improve early detection. GSE57065 and GSE95233 microarray data were used to screen differentially expressed genes (DEGs) in SS. Gene Ontology and KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway enrichment analyses of DEGs were performed, and correlations between immune cell and pathway enrichment scores were analyzed. The predictive value of candidate genes was evaluated by receiver operating characteristic (ROC) curves. GSE66099, GSE4607, and GSE13904 datasets were used for external validation. Blood samples from six patients and six controls were collected for validation by qRT-PCR and western blotting. In total, 550 DEGs in SS were identified; these genes were involved in the immune response, inflammation, and infection. Immune-related pathways and levels of infiltration of CD4 + TCM, CD8 + T cells, and preadipocytes differed between SS cases and controls. Seventeen genes were identified as potential biomarkers of SS (areas under ROC curves >0.9). The downregulation of CD8A, CD247, CD3G, LCK, and HLA-DRA in SS was experimentally confirmed. We identified several immune-related biomarkers in SS that may improve early identification of disease risk.

Targeted Activation of HNF4α by AMPK Inhibits Apoptosis and Ameliorates Neurological Injury Caused by Cardiac Arrest in Rats.

Previous studies have shown that AMPK plays an important role in cerebral ischemia-reperfusion injury by participating in apoptosis, but the exact mechanism and target of action remains unclear. This study aimed to investigate the protective mechanism of AMPK activation on brain injury secondary to cardiac arrest. HE, Nills and TUNEL assays were used to evaluate neuronal damage and apoptosis. The relationships between AMPK, HNF4α and apoptotic genes were verified by ChIP-seq, dual-luciferase and WB assays. The results showed that AMPK improved the 7-day memory function of rats, and reduced neuronal cell injury and apoptosis in the hippocampal CA1 region after ROSC, while the use of HNF4α inhibitor weakened the protective effect of AMPK. Further research found that AMPK positively regulated the expression of HNF4α, and AMPK could promote the expression of Bcl-2 and inhibit the expression of Bax and Cleaved-Caspase 3. In vitro experiments showed that AMPK ameliorated neuronal injury by inhibiting apoptosis through the activation of HNF4α. Combined with ChIP-seq, JASPAR analysis and Dual-luciferase assay, the binding site of HNF4α to the upstream promoter of Bcl-2 was found. Taken together, AMPK attenuates brain injury after CA by activating HNF4α to target Bcl-2 to inhibit apoptosis.

Neuroprotective Effect of miR-483-5p Against Cardiac Arrest-Induced Mitochondrial Dysfunction Mediated Through the TNFSF8/AMPK/JNK Signaling Pathway.

Substantial morbidity and mortality are associated with postcardiac arrest brain injury (PCABI). MicroRNAs(miRNAs) are essential regulators of neuronal metabolism processes and have been shown to contribute to alleviated neurological injury after cardiac arrest. In this study, we identified miRNAs related to the prognosis of patients with neurological dysfunction after cardiopulmonary resuscitation based on data obtained from the Gene Expression Omnibus (GEO) database. Then, we explored the effects of miR-483-5p on mitochondrial biogenesis, mitochondrial-dependent apoptosis, and oxidative stress levels after ischemia‒reperfusion injury in vitro and in vivo. MiR-483-5p was downregulated in PC12 cells and hippocampal samples compared with that in normal group cells and hippocampi. Overexpression of miR-483-5p increased the viability of PC12 cells after ischemia‒reperfusion injury and reduced the proportion of dead cells. A western blot analysis showed that miR-483-5p increased the protein expression of PCG-1, NRF1, and TFAM and reduced the protein expression of Bax and cleaved caspase 3, inhibiting the release of cytochrome c from mitochondria and alleviating oxidative stress injury by inhibiting the production of ROS and reducing MDA activity. We confirmed that miR-483-5p targeted TNFSF8 to regulate the AMPK/JNK pathway, thereby playing a neuroprotective role after cardiopulmonary resuscitation. Hence, this study provides further insights into strategies for inhibiting neurological impairment after cardiopulmonary resuscitation and suggests a potential therapeutic target for PCABI.

Establishment of a nonshockable rhythm cardiac arrest model caused by asphyxia.

OBJECTIVE: Cardiac arrest (CA) is caused by a nonshockable rhythm with a low success rate of return of spontaneous circulation (ROSC) and a poor prognosis. This study intended to establish a nonshockable rhythm CA model caused by asphyxia. MATERIALS AND METHODS: Healthy adult male Wistar rats were injected with vecuronium bromide to induce CA. After the CA duration reached the target time point, cardiopulmonary resuscitation was performed. The survival status and neurological and cardiac function were evaluated after ROSC. Brain histopathology, including hematoxylin staining, Nissl staining and Terminal dUTP nick-end labeling (TUNEL) staining, was performed to evaluate the surviving cells and apoptotic cells. Apoptosis-related proteins after ROSC for 72 h were analyzed by western blot. RESULTS: CA was successfully induced in all animals. The time for the three groups of animals to PEA was 320 ± 22 s in the CA-8 group, 322 ± 28 s in the CA-12 group and 320 ± 18 s in the CA-15 group. The time to asystole was 436 ± 54 s in the CA-8 group, 438 ± 62 s in the CA-12 group and 433 ± 56 s in the CA-15 group. The NDS of rats in the CA group was significantly decreased after ROSC for 24 h. The NDS in the CA-15 group was 5-16 points, while it was 58-67 points and 15-43 points in the CA-8 and CA-12 groups, respectively. The cardiac function of animals in the CA group was impaired after ROSC, and the ejection fraction, fractional shortening, stroke volume and cardiac output, were all significantly decreased. Brain histopathology showed that the number of surviving neurons was decreased, and the number of apoptotic cells was increased in CA group, the longer the CA duration, the more apoptotic cells increased. The expression of the proapoptotic protein Bax and the apoptotic executive protein caspase3 in the hippocampus of CA rats was significantly increased, while the expression of the antiapoptotic protein Bcl-2 was significantly reduced. CONCLUSIONS: The use of vecuronium can successfully induce CA caused by nonshockable rhythm in rats, which will help to further study the pathophysiological changes after CA by nonshockable rhythm.

High-Sensitivity Troponin I is an Indicator of Poor Prognosis in Patients with Severe COVID-19 Related Pneumonia.

Objective: Critical covid-19 patients have complications with acute myocardial injury is still unclear. We observed a series of critically ill patients, paying particular attention to the impact of myocardial injury at admission on short-term outcome. Methods: We prospectively collected and analyzed data from a series of severe covid-19 patients confirmed by real-time RT-PCR. Data were obtained from electronic medical records including clinical charts, nursing records, laboratory findings, and chest x-rays were from Feb 8, 2020, to April 7, 2020. The Acute Physiology and Chronic Health Evaluation (APACHE II) score, CURB-65 Pneumonia Severity Score, Sequential Organ Failure Assessment (SOFA) Score and pneumonia severity index (PSI) score were made within 24 hours of admission. Cardiac injury was diagnosed as hs-cTnI were above >28 pg/mL. The short-term outcome was defined as mortality in hospital. Results: A total of 100 patients met the diagnostic criteria of severe patients with COVID-19 during 2020.02.08-2020.04.07. The CURB 65, APACH2, SOFA, and PSI score were significantly higher in Critical group than in Severe group. Univariate regression analysis showed that oxygen flow, PO2/FiO2, SOFA and hs-cTnI were closely related to short-term outcome. The corresponding ROC of hs-cTnI, oxygen flow and SOFA for patient death prediction were 0.949, 0.906 and 0.652. hs-cTnI at 47.8 ng/liter predicted death, sensitivity 92.8%, specificity 92.9%; Oxygen flow at 5.5 liter/minute predicted death sensitivity 100%, specificity 77.9%; SOFA score at 5 predicted death sensitivity 100%, specificity 73.8%. Conclusion: Our cohort study demonstrated that inhaled oxygen flow, SOFA score, and myocardial injury at admission in critically ill COVID-19 patients were important indicators for predicting short-term death of patients, the hs-cTnI can be as a risk stratification, which may provide a simple method for the physicians to identify high-risk patients and give reasonable treatment in time.

Identification and Validation of Novel Potential Pathogenesis and Biomarkers to Predict the Neurological Outcome after Cardiac Arrest.

Predicting neurological outcomes after cardiac arrest remains a major issue. This study aimed to identify novel biomarkers capable of predicting neurological prognosis after cardiac arrest. Expression profiles of GSE29540 and GSE92696 were downloaded from the Gene Expression Omnibus (GEO) database to obtain differentially expressed genes (DEGs) between high and low brain performance category (CPC) scoring subgroups. Weighted gene co-expression network analysis (WGCNA) was used to screen key gene modules and crossover genes in these datasets. The protein-protein interaction (PPI) network of crossover genes was constructed from the STRING database. Based on the PPI network, the most important hub genes were identified by the cytoHubba plugin of Cytoscape software. Eight hub genes (RPL27, EEF1B2, PFDN5, RBX1, PSMD14, HINT1, SNRPD2, and RPL26) were finally screened and validated, which were downregulated in the group with poor neurological prognosis. In addition, GSEA identified critical pathways associated with these genes. Finally, a Pearson correlation analysis showed that the mRNA expression of hub genes EEF1B2, PSMD14, RPFDN5, RBX1, and SNRPD2 were significantly and positively correlated with NDS scores in rats. Our work could provide comprehensive insights into understanding pathogenesis and potential new biomarkers for predicting neurological outcomes after cardiac arrest.

Tandem mass tag-based proteomics analysis of protein changes in the freezing and thawing cycles of Trachurus murphyi.

We investigated the proteome variations in Trachurus murphyi with different cycles of freezing and thawing (FT) under frozen storage. A total of 2,482 proteins were assessed quantitatively, of which 269 proteins were recognized as differential abundance proteins during the second FT cycle until the eighth FT cycle. Bioinformatics analysis on gene ontology (GO) functional annotation and Kyoto Encyclopedia of Genes and Genomes pathway analyses of Differential Analysis of Proteins (DAPs) indicated multiple DAPs engaged with the protein structure, metabolic enzymes, and protein turnover. In addition, some of the observed proteins were probably the underlying markers of protein oxidation (PO). The analysis of PO sites revealed the sites of PO, such as amino adipic semialdehydes, γ-glutamic semialdehydes, and Schiff bases. Bioinformatics analyses demonstrated the involvement of differentially expressed proteins in the Hippo signaling pathway (Ko04390), indicating strong protein degradation with greater numbers of FT cycles under frozen storage. It provides an insight into quality stability from a proteomics quality perspective at the molecular level. The results obtained have deepened our current understandings of the mechanisms that reveal variations in proteomes and quality, as well as help promote quality control of T. murphyi across the cold transportation chain. PRACTICAL APPLICATION: Temperature fluctuation is one of the core issues during frozen food storage and distribution faced by the frozen food industry. Fluctuation may result in microstructural changes, ice recrystallization, and protein change in frozen food products. Tandem mass tag-based methods were adopted to study proteome variations in Trachurus murphyi muscles under different cycles of freezing and thawing under frozen storage conditions in this paper. The results obtained have deepened our current understandings of the mechanisms that reveal variations in proteomes and quality, as well as help promote quality control of T. murphyi across the cold transportation chain.

Hypothermia preconditioning improves cardiac contractility after cardiopulmonary resuscitation through AMPK-activated mitophagy.

Hypothermia preconditioning (HPC) improves cardiac function after cardiac arrest, yet the mechanism is unclear. We hypothesized that HPC-activated adenosine monophosphate-activated protein kinase (AMPK) activity may be involved. Adult male Wistar rats were randomly divided into normothermia Control, HPC (cooling to 32-34°C for 30 min), and HPC + Compound C (Compound C 10 mg/kg was injected intraperitoneally 30 min before HPC group). The rats underwent 7 min of untreated ventricular fibrillation (VF) followed by cardiopulmonary resuscitation (CPR). Cardiac function and hemodynamic parameters were evaluated at 4 h after return of spontaneous circulation (ROSC). Survival status was determined 72 h after ROSC. Mechanistically, we further examined the AMPK-Unc-51 Like Autophagy Activating Kinase 1 (ULK1)-mitophagy pathway and autophagic flux in vivo and in vitro. Six of twelve rats in the Control group, 10 of 12 rats in the HPC group, and 7 of 12 rats in HPC + Compound C group were successfully resuscitated. The 72-h survival rates were 1 of 12 Control, 6 of 12 HPC, and 2 of 12 HPC + Compound C rats, respectively (P = 0.043). Rats in the HPC group demonstrated greater cardiac contractility and hemodynamic stability which were compromised by Compound C. Furthermore, HPC increased the protein levels of p-AMPKα and p-ULK1 and promoted the expression of mitochondrial autophagy-related genes. Compound C decreased the expression of mitochondrial autophagy-related genes and reduced autophagic flux. Consistent with the observations obtained in vivo, in vitro experiments in cultured neonatal rat cardiomyocytes (CMs) demonstrated that HPC attenuated simulated ischemia-reperfusion-induced CM death, accompanied by increased AMPK-ULK1-mitophagy pathway activity. These findings suggest that AMPK-ULK1-mitophagy pathway was activated by HPC and has a crucial role in cardioprotection during cardiac arrest. Manipulation of mitophagy by hypothermia may merit further investigation as a novel strategy to prevent cardiac ischemia-reperfusion injury.

Hemodynamic Characteristics of Patients with Myocardial Injury and Cardiogenic Shock Caused by Severe COVID-19-Related Pneumonia.

OBJECTIVE: To observe hemodynamic characteristics in a series of patients with myocardial injury caused by severe COVID-19-related pneumonia. MATERIALS AND METHODS: We continuously collected clinical data from severe COVID-19-related pneumonia patients from the West Campus of Union Hospital in Wuhan and Dongguan People's Hospital in Dongguan to explore the prevalence of myocardial injury and hemodynamic characteristics after circulatory failure. Doppler ultrasound and PiCCO2 were used to evaluate the hemodynamics of each patient, and arterial blood gas analysis was performed at the same time. Pearson correlation analysis was used to clarify the relationship between the parameters. RESULTS: A total of 376 patients were observed during the study period. Eighty-seven patients had myocardial injury after admission, and the mean time of myocardial injury after admission was 6 (2, 30) days, from which 16 patients developed hemodynamic instability and 15 died of cardiogenic shock or combined with MODS. Cardiac echocardiography found that the LVEF of all patients was in the normal range and that diastolic function was slightly to moderately impaired. The PiCCO2 data showed that the GEF was significantly decreased in all patients. The dpmx was in normal range. EVLWI, SVRI and GEDI were significantly increased in most patients. Pearson correlation analysis showed that cTNI was significantly related to BNP at hemodynamic instability (r = 0.662, p = 0.005); GEF was related to EVLWI (r = -0.572, p = 0.021) and LAC (r = 0.692, p = 0.003); and EVLWI was affected by LVEF (r = -0.564, p = 0.023), LVDF (r = -0.734, p = 0.001) and PVPI (r = -0.524, p = 0.037). CONCLUSION: Hemodynamic status after myocardial injury and cardiogenic shock caused by severe COVID-19-related pneumonia was characterized by cardiac preload and increased EVLWI, accompanied by a decline in GEF.

The tempo of Ediacaran evolution.

The rise of complex macroscopic life occurred during the Ediacaran Period, an interval that witnessed large-scale disturbances to biogeochemical systems. The current Ediacaran chronostratigraphic framework is of insufficient resolution to provide robust global correlation schemes or test hypotheses for the role of biogeochemical cycling in the evolution of complex life. Here, we present new radio-isotopic dates from Ediacaran strata that directly constrain key fossil assemblages and large-magnitude carbon cycle perturbations. These new dates and integrated global correlations demonstrate that late Ediacaran strata of South China are time transgressive and that the 575- to 550-Ma interval is marked by two large negative carbon isotope excursions: the Shuram and a younger one that ended ca. 550 Ma ago. These data calibrate the tempo of Ediacaran evolution characterized by intervals of tens of millions of years of increasing ecosystem complexity, interrupted by biological turnovers that coincide with large perturbations to the carbon cycle.

Percutaneous Coronary Intervention After Return of Spontaneous Circulation Reduces the In-Hospital Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiac Arrest.

BACKGROUND AND OBJECTIVE: The role of percutaneous coronary intervention (PCI) after return of spontaneous circulation (ROSC) in patients with acute myocardial infarction (AMI) complicated by cardiac arrest (CA) is controversial. This study aimed to evaluate the effects of PCI on the in-hospital mortality after ROSC in patients with AMI complicated by CA. METHODS: The clinical data of 66 consecutive patients with ROSC after CA caused by AMI from January 2006 to December 2015 at the First Affiliated Hospital of Sun Yat-sen University were collected. Among these patients, 21 underwent urgent PCI. We analyzed the clinical characteristics of the patients during hospitalization. RESULTS: The patients who underwent PCI had a higher rate of ST-segment elevation, and their initial recorded heart rhythms were more likely to have a shockable rhythm. Further, they had a high PCI success rate of 100%. The in-hospital mortality in the patients who did not undergo PCI was significantly higher than that in the patients who underwent PCI (68.9% vs 9.5%, P<0.05). Multivariate logistic regression analysis showed that cardiogenic shock (odds ratio [OR], 3.537; 95% CI, 1.047-11.945; P=0.042) and Glasgow Coma Scale score of ≤8 after ROSC (OR, 14.992; 95% CI, 2.815-79.843; P=0.002) were the independent risk factors for in-hospital mortality among the patients. Meanwhile, PCI was a protective factor against in-hospital mortality (OR, 0.063; 95% CI, 0.012-0.318; P=0.001). After propensity matching analysis, the results still showed that PCI (OR, 0.226; 95% CI, 0.028-1.814; P=0.0162) was a protective factor for in-hospital death. CONCLUSION: The patients with ROSC after CA caused by AMI who underwent PCI had a lower in-hospital mortality than those who did not undergo PCI.

The Effect of Multiple Freeze-Thaw Cycles on the Microstructure and Quality of Trachurus murphyi.

Temperature fluctuation in frozen food storage and distribution is the perpetual and core issue faced by the frozen food industry. Ice recrystallisation induced by temperature fluctuations under cold storage causes microstructural changes in fish products and irreversible damages to cells and tissues, which lower the frozen fish quality in the food chain. This study is intended to explore how repeated freezing-thawing affected the microstructure and quality of Trachurus murphyi during its frozen storage. The results showed the consistency between the increase in ice crystal diameter, volume, and porosity in frozen fish and the increase in centrifugal loss (from 22.4% to 25.69%), cooking loss (from 22.32% to 25.19%), conductivity (from 15.28 Ms/cm to 15.70 Ms/cm), TVB-N (from 16.32 mg N/100 g to 19.94 mg N/100 g), K-value (from 3.73% to 7.07%), and amino acid composition. The muscle structure change observed by Fourier-Transform Infrared spectroscopy (FT-IR) showed that the content of α-helix reduced from 59.05% to 51.83%, while the ß-sheet fraction grew from 15.44% to 17.11%, ß-turns increased from 5.45% to 7.58%, and random coil from 20.06% to 23.49%. Moreover, muscular structure exhibited varying degrees of deterioration with increasing cycles of freezing and thawing as shown by scanning electron microscopy (SEM). We studied the muscular morphology, which included the measurement of porosities (%) of pore that increased (from 1.4% to 4.3%) and pore distribution, by X-ray computed tomography (uCT). The cycles of the freeze-thaw resulted in structural changes, which seemed to be closely associated with ultimate quality of frozen fish products.

Mesenteric Lymph Duct Drainage Attenuates Lung Inflammatory Injury and Inhibits Endothelial Cell Apoptosis in Septic Rats.

The present study was to investigate the effect of mesenteric lymph duct drainage on lung inflammatory response, histological alteration, and endothelial cell apoptosis in septic rats. Animals were randomly assigned into four groups: control, sham surgery, sepsis, and sepsis plus mesenteric lymph drainage. We used the colon ascendens stent peritonitis (CASP) procedure to induce the septic model in rats, and mesenteric lymph drainage was performed with a polyethylene (PE) catheter inserted into mesenteric lymphatic. The animals were sacrificed at the end of CASP in 6 h. The mRNA expression levels of inflammatory mediators were measured by qPCR, and the histologic damage were evaluated by the pathological score method. It was found that mesenteric lymph drainage significantly reduced the expression of TNF-α, IL-1ß, and IL-6 mRNA in the lung. Pulmonary interstitial edema and infiltration of inflammatory cells were alleviated by mesenteric lymph drainage. Moreover, increased mRNA levels of TNF-α, IL-1ß, IL-6 mRNA, and apoptotic rate were observed in PMVECs treated with septic lymph. These results indicate that mesenteric lymph duct drainage significantly attenuated lung inflammatory injury by decreasing the expression of pivotal inflammatory mediators and inhibiting endothelial apoptosis to preserve the pulmonary barrier function in septic rats.

Intravenous versus intraosseous adrenaline administration in out-of-hospital cardiac arrest: A retrospective cohort study.

BACKGROUND: Adrenaline is an important component in the resuscitation of individuals experiencing out-of-hospital cardiac arrest (OHCA). The 2018 Advanced Cardiac Life Support (ACLS) algorithm gives the option of either intravenous (IV) or intraosseous (IO) routes for adrenaline administration during cardiac arrest. However, the optimal route during prehospital resuscitation remains controversial. This study aims to investigate whether IV and IO routes lead to different outcomes in OHCA patients who received prehospital adrenaline. METHODS: This retrospective analysis included adult patients with OHCA of presumed cardiac origin who had Emergency Medical Services (EMS) CPR, received adrenaline, and were enrolled in the Resuscitation Outcomes Consortium (ROC) Cardiac Epistry version 3 database between 2011 and 2015. We divided the study population into IV and IO groups based on the administration route. Logistic regression analysis was performed to evaluate the association between adrenaline delivery routes and prehospital return of spontaneous circulation (ROSC), survival to hospital discharge, and favorable neurological outcome. RESULTS: Of the 35,733 patients included, 27,758 (77.7%) had adrenaline administered via IV access and 7975 (22.3%) via IO access. With the IO group as a reference in the logistic regression model, the adjusted odds ratios of the IV group for prehospital ROSC, survival and favorable neurological outcome were 1.367 (95%CI, 1.276-1.464), 1.468 (95%CI, 1.264-1.705) and 1.849 (95%CI, 1.526-2.240), respectively. Similar results were found in the propensity score matched population and subgroup analysis. CONCLUSION: Compared with the IO approach, the IV approach appears to be the optimal route for adrenaline administration in advanced life support for OHCA during prehospital resuscitation.

Enhanced external counterpulsation improves cardiac function in Beagles after cardiopulmonary resuscitation.

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Enhanced external counterpulsation improves cardiac function in Beagles after cardiopulmonary resuscitation

The aim of this study was to investigate the influence of enhanced external counterpulsation (EECP) on the cardiac function of beagle dogs after prolonged ventricular fibrillation. Twenty-four adult male beagles were randomly divided into control and EECP groups. Ventricular fibrillation was induced in the animals for 12 min, followed by 2 min of cardiopulmonary resuscitation. They then received EECP therapy for 4 h (EECP group) or not (control group). The hemodynamics was monitored using the PiCCO2 system. Blood gas and hemorheology were assessed at baseline and at 1, 2, and 4 h after return of spontaneous circulation (ROSC). The myocardial blood flow (MBF) was quantified by 18F-flurpiridaz PET myocardial perfusion imaging at baseline and 4 h after ROSC. Survival time of the animals was recorded within 24 h. Ventricular fibrillation was successfully induced in all animals, and they achieved ROSC after cardiopulmonary resuscitation. Survival time of the control group was shorter than that of the EECP group [median of 8 h (min 8 h, max 21 h) vs median of 24 h (min 16 h, max 24 h) (Kaplan Meyer plot analysis, P=0.0152). EECP improved blood gas analysis findings and increased the coronary perfusion pressure and MBF value. EECP also improved the cardiac function of Beagles after ROSC in multiple aspects, significantly increased blood flow velocity, and decreased plasma viscosity, erythrocyte aggregation index, and hematocrit levels. EECP improved the hemodynamics of beagle dogs and increased MBF, subsequently improving cardiac function and ultimately improving the survival time of animals after ROSC.

Mild hypothermia improves neurological outcome in mice after cardiopulmonary resuscitation through Silent Information Regulator 1-actviated autophagy.

Mild hypothermia treatment (MHT) improves the neurological function of cardiac arrest (CA) patients, but the exact mechanisms of recovery remain unclear. Herein, we generated a CA and cardiopulmonary resuscitation (CPR) mouse model to elucidate such function. Naïve mice were randomly divided into two groups, a normothemia (NT) group, in which animals had normal body temperature, and a MHT group, in which animals had a body temperature of 33 °C (range: 32-34 °C), after the return of spontaneous circulation (ROSC), followed by CA/CPR. MHT significantly improved the survival rate of CA/CPR mice compared with NT. Mechanistically, MHT increased the expression of Silent Information Regulator 1 (Sirt1) and decreased P53 phosphorylation (p-P53) in the cortex of CA/CPR mice, which coincided with the elevated autophagic flux. However, Sirt1 deletion compromised the neuroprotection offered by MHT, indicating that Sirt1 plays an important role. Consistent with the observations obtained from in vivo work, our in vitro study utilizing cultured neurons subjected to oxygen/glucose deprivation and reperfusion (OGD/R) also indicated that Sirt1 knockdown increased OGD/R-induced neuron necrosis and apoptosis, which was accompanied by decreased autophagic flux and increased p-P53. However, the depletion of P53 did not suppress neuron death, suggesting that P53 was not critically involved in MHT-induced neuroprotection. In contrast, the application of autophagic inhibitor 3-methyladenine attenuated MHT-improved neuron survival after OGD/R, further demonstrating that increased autophagic flux significantly contributes to MHT-linked neuroprotection of CA/CRP mice. Our findings indicate that MHT improves neurological outcome of mice after CA/CPR through Sirt1-mediated activation of autophagic flux.

miR-26a prevents neural stem cells from apoptosis via ß-catenin signaling pathway in cardiac arrest-induced brain damage.

Neural stem cells (NSCs) transplantation is one of the most promising strategies for the treatment of CA-induced brain damage. The transplanted NSCs could differentiate into new neuron and replace the damaged one. However, the poor survival of NSCs in severe hypoxic condition is the limiting step to make the best use of this kind of therapy. In the present study, we investigated whether the overexpression of miR-26a improves the survival of NSCs in hypoxic environment in vitro and in vivo. In vitro hypoxia injury model is established in NSCs by CoCl2 treatment, and in vivo cardiac arrest (CA) model is established in Sprague-Dawley (SD) rats. Quantitative real-time polymerase chain reaction is used to detect the mRNA level and Western blot is used to examine the protein level of indicated genes. TUNEL staining and flow cytometry are applied to evaluate apoptosis. Dual-luciferase reporter assay is utilized to analyze the target gene of miR-26a. The expression of miR-26a is reduced in both in vitro and in vivo hypoxic model. MiR-26a directly targets 3'-UTR of glycogen synthase kinase 3ß (GSK-3ß), resulting in increased ß-catenin expression and decreased apoptosis of NSCs. Overexpression of miR-26a in transplanted NSCs improves the survival of NSCs and neurological function in CA rats. MiR-26a prevents NSCs from apoptosis by activating ß-catenin signaling pathway in CA-induced brain damage model. Modulating miR-26a expression could be a potential strategy to attenuate brain damage induced by CA.