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The objective of this study is to explore the changes in the coagulation and fibrinolysis system in an animal model with pulmonary embolism after cardiopulmonary bypass and to provide a theoretical basis for clinical practice. An animal model of cardiac arrest due to pulmonary embolism was established for venous thrombus (10‐15 mL) in the left external jugular vein of 21 pigs. Computed tomography (CT) pulmonary arteriography was performed after the recovery of the underlying state, cardiac arrest state and spontaneous circulation, and then thrombolysis and cardiopulmonary resuscitation (recombinant tissue plasminogen activator [t‐PA] 50 mg) were performed immediately. The changes of tissue factor (TF), tissue factor pathway inhibitor (TFPI), t‐PA and plasminogen activator inhibitor‐1 (PAI‐1) in the blood were detected by ELISA. The blood samples were collected immediately, 1, 2, 4 and 6 hours after the recovery of spontaneous circulation. Data from animals that were successfully resuscitated at different time points were compared using a repeated measures one‐way analysis of variance. Seventeen pigs had cardiac arrest after 10 to 15 mL of thrombus injection, and the other four had cardiac arrest after 5 to 8 mL of additional thrombus. Nine pigs survived 6 hours of cardiopulmonary resuscitation. CT pulmonary angiogram showed pulmonary artery obstruction. TF levels were increased compared with basal status, but there was no statistical difference (P >.05). TFPI levels were higher at 1, 2, 4 and 6 hours after recovery of spontaneous circulation compared with basal state (P <.05); t‐PA levels were higher at cardiac arrest, and immediately after recovery of spontaneous circulation compared with basal state. There was a statistical difference in PAI‐1 level at 1, 2, 4 and 6 hours after recovery of spontaneous circulation (P <.05). There was no statistical difference in PAI‐1 level at each stage compared with basal state (P >.05). TFPI has a certain influence on the coagulation and thrombosis regulation of the body, and the increase in fibrinolytic activity has a positive promoting effect on the thrombolysis. It provided the theoretical basis of clinical treatment of thrombotic diseases. [ABSTRACT FROM AUTHOR]

The present study aimed to explore the protective effects of extracorporeal membrane oxygenation (ECMO) on intestinal mucosal injury following cardiopulmonary resuscitation (CPR), and to assess the potential mechanisms involved. A total of 24 healthy adult domestic pigs were selected as the study subjects. A ventricular fibrillation model was induced through programmed electric stimulation. Subsequently, the animals were randomly divided into conventional CPR and CPR+ECMO groups (n=12 per group). The mortality and hemodynamic parameters of the two groups were compared. The expression levels of inflammatory cytokines in the serum and intestinal mucosa were detected by ELISAs. The intestinal mucosa was subjected to hematoxylin and eosin, and immunohistochemical staining, followed by electron microscopy, to assess the degree of apoptosis and necrosis. The animals in both groups recovered from the programmed ventricular fibrillation. In the CPR group, two animals died at 2 h and two more animals died a further 2 h later, resulting in a 33.3% mortality rate, whereas no cases of mortality were observed in the CPR+ECMO group. Compared with the animals in the CPR group, the hemodynamic parameters of the animals in the CPR+ECMO group revealed significantly improved outcomes. Multiple inflammatory factors (tumor necrosis factor α, interleukin-1 and interleukin-6), myeloperoxidase and malondialdehyde levels were decreased, whereas Na/Ca-ATPase and superoxide dismutase levels were elevated in the intestinal mucosa of animals in the CPR+ECMO group compared with those in the CPR group. Additionally, pathological staining demonstrated that the intestinal mucosa tissue in the CPR+ECMO group exhibited less apoptosis, necrosis and inflammatory cell infiltration, which was further supported by a decrease in Bax expression and an increase in Bcl-2 expression. Overall, ECMO after CPR reduced the intestinal mucosal barrier injury after spontaneous circulation recovery, and the mechanism involved decreased inflammation and apoptosis. [ABSTRACT FROM AUTHOR]

Abstract This study was aimed at a serial evaluation of the prognostic values of initial shockable rhythm, bystander cardiopulmonary resuscitation (CPR) and gender for neurological outcome and survival in adults treated with targeted temperature management (TTM) following cardiac arrest (CA). PubMed, Embase and the Cochrane Library were searched for eligible studies. Pooled odds ratio (OR) with 95% confidence intervals (CIs) was calculated to evaluate prognostic values using RevMan 5.3. The outcomes were favorable neurological outcome (defined as cerebral performance category of 1 and 2) and survival. Seventeen studies were subjected to the meta-analysis. Favorable neurological outcome was associated with significantly higher odds of an initial shockable rhythm (OR: 7.63, 95%CI: 6.51–8.96), bystander CPR (OR: 1.44, 95%CI: 1.14–1.82), male (OR: 1.39, 95%CI: 1.20–1.61). Survival was associated with higher odds of an initial shockable rhythm (OR: 4.88, 95%CI: 3.18–4.79), higher odds of bystander CPR (OR: 1.71, 95%CI: 1.05–2.77). No significant association was found between survival and male. In adult patients treated with TTM, initial shockable rhythm, bystander CPR and male sex were associated with a higher likelihood of favorable neurological outcome. Initial shockable rhythm and bystander CPR were associated with a higher likelihood of survival. These factors could help in identifying patients who are eligible for TTM. [ABSTRACT FROM AUTHOR]

Abstract: Immune disorders are an important feature of patients with out‐of‐hospital cardiac arrest (OHCA) after return of spontaneous circulation (ROSC). However, the precise immune alterations in patients with OHCA that occur immediately after ROSC are unclear. In this study, we investigated human leucocyte antigen‐DR (HLA‐DR) expression on circulatory monocytes and B and T lymphocytes. Sixty‐eight consecutive patients with OHCA with ROSC >12 hours were enrolled. Clinical data and 28‐day survival were recorded. Peripheral blood samples after ROSC days 1 and 3 were analysed to evaluate HLA‐DR expression. Fifty healthy individuals were enrolled as controls. Compared with levels in healthy individuals, HLA‐DR expression on monocytes and B lymphocytes, but not on T lymphocytes, decreased on days 1 and 3 after ROSC. No significant difference in HLA‐DR expression was detected between survivors and non‐survivors on day 1. For 41 patients with expression data for days 1 and 3, HLA‐DR expression on monocytes and B lymphocytes in non‐survivors was lower than that in survivors on day 3. In non‐survivors, the mean fluorescence intensities of HLA‐DR on B lymphocytes and percentages of HLA‐DR+ T lymphocytes were lower on day 3 than on day 1. On days 1 and 3, there were significant correlations between HLA‐DR expression on monocytes and B lymphocytes and clinical indicators, such as time to ROSC, adrenaline dose, acute physiology, chronic health evaluation II and the sequential organ failure assessment. The decreases in HLA‐DR expression on circulatory monocytes and B and T lymphocytes after ROSC may be involved in the observed immunosuppression in patients with OHCA. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to clarify whether therapeutic hypothermia protects against cerebral edema following cardiac arrest (CA) and cardiopulmonary resuscitation (CPR) in a porcine model via regulating the angiopoietin-Tie-2 ligand-receptor system.Methods: Male pigs were randomized into the therapeutic hypothermia group, the normothermia group or the sham control group. CA was induced in pigs by untreated ventricular fibrillation for 8min. Brain edema was determined by measuring the cerebral cortical water content at 24h after the return of spontaneous circulation (ROSC). The serum levels of angiopoietin-1 (Ang-1), angiopoietin-2 (Ang-2), tyrosine kinase with immunoglobulin-like loop epidermal growth factor homology domain 2 (Tie-2), and S100B were measured using enzyme immunoassay kits at 0.5, 6, 12 and 24h after ROSC. The levels of the Ang-1, Ang-2, phosphorylated Tie-2 and Tie-2 proteins in the cerebral cortex at 24h after ROSC were determined by Western blotting.Results: Therapeutic hypothermia lessened brain cortex edema, alleviated histopathology injury, and improved neurologic outcomes at 24h after ROSC. Therapeutic hypothermia inhibited the CA- and CPR-induced increases in serum Ang-2 protein expression and the Ang-2/Ang-1 ratio and attenuated the decrease in serum Ang-1 expression. Therapeutic hypothermia also increased the protein expression of Ang-1 and the phosphorylated Tie-2/Tie-2 ratio and inhibited the expression of Ang-2 in the cerebral cortex at 24h after ROSC.Conclusions: Based on our experiment, therapeutic hypothermia decreased cerebral edema after CA, which may be, at least in part, related to its ability to modulate the expression of components of the Ang-Tie-2 system. [ABSTRACT FROM AUTHOR]

Objective: Gasping is common after cardiac arrest, and its frequency decreases over time. The aim of this study was to conduct a meta-analysis to evaluate the association of gasping and survival to discharge in patients who suffered out-of-hospital cardiac arrest.Methods: Relevant studies were identified by searching in PubMed, Medline, Embase, OVID, Web of Science and Google Scholar. Risk ratios (RR) and 95% confidence intervals (CI) were calculated to assess the association of gasping and on out-of-hospital cardiac arrest outcomes. Heterogeneity, subgroup analysis, sensitivity analysis and publication bias were explored.Results: Individual patient data was obtained from 10,797 participants suffered out-of-hospital cardiac arrest in five cohort studies of 4 articles. A fixed effects model suggested that patients with gasping were 3.525 times (95% CI: 3.028-4.104; P<0.01) more likely to survive to discharge than those without gasping, and there was no heterogeneity among studies (P=0.564). Also it may be a favorable factor for return of spontaneous circulation (RR: 2.170; 95% CI: 1.691, 2.785) with high heterogeneity (Q=5.26; P=0.022).Conclusions: Findings of this meta-analysis demonstrated that gasping is common after cardiac arrest, and is associated with increased survival to discharge. Patients who are cardiac arrest with gasping should be promptly resuscitated. [ABSTRACT FROM AUTHOR]

Complement activation has been implicated in ischemia/reperfusion injury. This study aimed to determine whether mild hypothermia (HT) inhibits systemic and cerebral complement activation after resuscitation from cardiac arrest. Sixteen minipigs resuscitated from 8 minutes of untreated ventricular fibrillation were randomized into two groups: HT group (n=8), treated with HT (33°C) for 12 hours; and normothermia group (n=8), treated similarly as HT group except for cooling. Blood samples were collected at baseline and 0.5, 6, 12, and 24 hours after return of spontaneous circulation (ROSC). The brain cortex was harvested 24 hours after ROSC. Complement and pro-inflammatory markers were detected using enzyme-linked immunosorbent assay. Neurologic deficit scores were evaluated 24 hours after ROSC. C1q, Bb, mannose-binding lectin (MBL), C3b, C3a, C5a, interleukin-6, and tumor necrosis factor-α levels were significantly increased under normothermia within 24 hours after ROSC. However, these increases were significantly reduced by HT. Hypothermia decreased brain C1q, MBL, C3b, and C5a contents 24 hours after ROSC. Hypothermic pigs had a better neurologic outcome than normothermic pigs. In conclusion, complement is activated through classic, alternative, and MBL pathways after ROSC. Hypothermia inhibits systemic and cerebral complement activation, which may provide an additional mechanism of cerebral protection. [ABSTRACT FROM AUTHOR]

Background: Recent experimental and clinical studies have indicated that the β-adrenergic effect of epinephrine significantly increases the severity of post resuscitation myocardial dysfunction. The aim of the study was to investigate whether the short-acting β1-selective adrenergic blocking agent, esmolol, would attenuate post resuscitation myocardial dysfunction in a porcine model of cardiac arrest. Methods and Results: After 8 min of untreated ventricular fibrillation and 2 min of basic life support, 24 pigs were randomized to three groups (n = 8 per group), which received central venous injection of either epinephrine combined with esmolol (EE group), epinephrine (EP group), or saline (SA group). Hemodynamic status and blood samples were obtained at 0, 30, 60, 120, 240 and 360 min after return of spontaneous circulation (ROSC). Surviving pigs were euthanatized at 24 h after ROSC, and the hearts were removed for analysis by electron microscopy, Western blotting, quantitative real-time polymerase chain reaction, and terminal deoxynucleotidyl transferase–mediated dUTP nick end labeling (TUNEL) assay. Compared with the EP and SA groups, EE group had a better outcome in hemodynamic function, (improved dp/dt maxima and minima and cardiac output) (P<0.05), and improved oxygen metabolism (oxygen delivery and oxygen consumption) (P<0.05), which suggesting that EE can protect myocardial tissue from injury and improve post-resuscitation myocardial dysfunction. The protective effect of EE also correlated with reducing cardiomyocyte apoptosis, evidenced by reducing TUNEL-positive cells, increasing anti-apoptotic Bcl-2/Bax ratio and suppression of caspase-3 activity in myocardium. Conclusions: Esmolol, a short-acting β1-selective adrenergic blocking agent, given during CPR has significant effects on attenuating post resuscitation myocardial dysfunction. The current study provides a potential pharmacologic target for post resuscitation myocardial dysfunction. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that mild hypothermia is neuroprotective for comatose patients resuscitated from cardiac arrest, but the mechanism of this protection is not fully understood. The aim of this study was to determine whether prolonged whole-body mild hypothermia inhibits mitochondrial membrane permeability (MMP) in the cerebral cortex after return of spontaneous circulation (ROSC). Thirty-seven inbred Chinese Wuzhishan minipigs were successfully resuscitated after 8 minutes of untreated ventricular fibrillation (VF) and underwent recovery under normothermic (NT) or prolonged whole-body mild hypothermic (HT; 33°C) conditions for 24 or 72 hours. Cerebral samples from the frontal cortex were collected at 24 and 72 hours after ROSC. Mitochondria were isolated by differential centrifugation. At 24 hours, relative to NT, HT was associated with reductions in opening of the mitochondrial permeability transition pore, release of pro-apoptotic substances from mitochondria, caspase 3 cleavage, apoptosis, and neurologic deficit scores, as well as increases in mitochondrial membrane potential and mitochondrial respiration. Together, these findings suggest that mild hypothermia inhibits ischemia-induced increases in MMP, which may provide neuroprotection against cerebral injury after cardiac arrest. [ABSTRACT FROM AUTHOR]

Abstract: Background: Restoration of spontaneous circulation after cardiopulmonary resuscitation in cardiac arrest patients does not always signal a completely successful outcome. Functional deficiencies of the nervous system are found in many survivors of cardiac arrest. Objectives: To study the effects of dopamine-induced elevated blood pressure on the hemodynamics, oxygen metabolism, and cerebral resuscitation in different perfusion conditions in a resuscitated animal model. Methods: There were 18 pigs included in the study. Ventricular fibrillation (VF) was induced with a programmed electrical stimulation device. After 4 min of untreated ventricular fibrillation followed by 9 min of CPR, 12 animals were resuscitated successfully, and were then randomly assigned to either the study group (dopamine group) or the control group (normal perfusion group). All animals in the two groups received normal saline through continuous intravenous guttae for 4 h at a rate of 15 mL/kg/h. In the study group, dopamine was added to raise the animals'' blood pressure. Four hours of intensive monitoring was performed for all study animals. Finally, 24-h evaluation of neurological function was conducted in surviving animals in accordance with the standard of the Cerebral Performance Category Score. Results: In animals in the dopamine group, the cardiac output, mean aortic pressure, coronary perfusion pressure, oxygen delivery, and oxygen consumption were higher than those found in the animals in the normal perfusion group (p < 0.05). Oxygen metabolism was remarkably improved in animals in the dopamine group. Furthermore, cerebral perfusion was better in the dopamine group than in the control group and thus, results of the evaluation of nervous system function were better in animals treated with dopamine (p < 0.05). Conclusions: Dopamine improved systemic perfusion, cerebral blood supply, and oxygen metabolism after successful resuscitation from VF in a porcine model. All of these factors have profound effects on the cerebral resuscitation. [Copyright &y& Elsevier]

We used a wearable carotid Doppler patch to study carotid blood flow patterns in a porcine model of cardiac arrest to identify return of spontaneous circulation (ROSC) and hemodynamics associated with different arrhythmias and the quality of compressions. Twenty Landrace pigs were used as models of cardiac arrest following a standard protocol. Carotid blood flow was monitored continuously using noninvasive ultrasound. Carotid spectral waveforms were captured during various arrhythmias and CPR. Typical carotid blood flow waveforms were recorded at the time of ROSC, and hemodynamic changes were compared with carotid blood flow parameters. The results showed that the carotid blood flow waveforms varied with ventricular arrhythmia type. During CPR, compression depth correlated significantly with carotid maximal velocity (Vmax) (Spearman correlation coefficient (r) = 0.682, P < 0.001) and velocity–time integral (VTI) (r = 0.794, P < 0.001). Vmax and VTI demonstrated moderate predictive value for survival. The regular carotid blood flow pattern towards the brain was observed during ROSC, concurrent with compression waveforms. After ROSC, VTI and carotid pulse volume (cPV) showed similar trends as stroke volume (SV). The carotid minute volume (cMV) exhibited a similar trend as cardiac output (CO). Carotid blood flow monitoring could provide valuable information about different arrhythmias as well as the quality of CPR. Carotid flow monitoring allows for timely and effective identification of ROSC. In addition, it may provide valuable hemodynamic information after ROSC. [ABSTRACT FROM AUTHOR]

Aim: We aimed to assess the effects of Shenfu injection (SFI) in combination with epinephrine during cardiac arrest on survival and neurological outcome after out-of-hospital cardiac arrest (OHCA).Methods: In this randomised, assessor-blind controlled trial, Utstein-style data were collected from 1233 OHCA patients treated at the Beijing Emergency Medical Center between January 2013 and June 2016. The patients were randomised into either a treatment group that received a combination of SFI and standard treatment with epinephrine or a control group that received standard treatment with epinephrine alone. The primary outcome was survival to hospital admission. The secondary outcomes were return of spontaneous circulation (ROSC), survival to hospital discharge, favourable neurological outcome at discharge, survival to one year, and favourable neurological outcome at one-year survival.Results: In both groups, the survival to hospital admission, ROSC, survival to hospital discharge, and one-year survival rate after discharge from the hospital did not differ significantly. However, SFI achieved favourable neurological outcome at discharge in comparison with the standard treatment with an odds ratio (OR) of 2.72 at a 95% confidence interval (CI; 1.00-8.53). Meanwhile, unlike with epinephrine alone, the combination of SFI and epinephrine achieved a better cerebral performance category (CPC) score (1-2) after one-year survival (OR: 5.08, 95% CI: 1.07-47.80).Conclusion: The combination of SFI and epinephrine had favourable neurological outcomes after OHCA compared with those with epinephrine alone, whereas the survival to admission was not significantly altered. [ABSTRACT FROM AUTHOR]

Objectives: After return of spontaneous circulation, patients who experienced out-of-hospital cardiac arrest present an impaired innate immune response that resembles sepsis. Presepsin, a new biomarker for sepsis, has not been studied in out-of-hospital cardiac arrest patients. This study explored the role of presepsin in evaluating the prognosis and early innate immune alteration of out-of-hospital cardiac arrest patients after return of spontaneous circulation by observing presepsin levels, CD14, and human leukocyte antigen-DR expression on monocytes.Design: Retrospective analysis.Setting: The emergency department of an urban university tertiary hospital.Participants: One hundred sixty-five out-of-hospital cardiac arrest patients with return of spontaneous circulation more than 12 hours, and 100 healthy individuals.Interventions: None.Measurements and Main Results: Plasma presepsin and procalcitonin levels were tested after resuscitation (day 0) and on days 1 and 3 after return of spontaneous circulation. Presepsin levels were higher in out-of-hospital cardiac arrest patients than in healthy individuals. In the first 3 days, presepsin and procalcitonin levels were persistently lower in 28-day survivors and patients with favorable neurologic outcome patients than in 28-day nonsurvivors and patients with unfavorable neurologic outcome. On days 0, 1, and 3, different cut-off values of presepsin showed prognostic value for 28-day mortality and favorable neurologic outcomes similar to procalcitonin. CD14 and human leukocyte antigen-DR expression on monocytes were analyzed by flow cytometry. Compared with controls, CD14 expression in out-of-hospital cardiac arrest patients increased on day 1 and began to decrease on day 3, whereas human leukocyte antigen-DR+ monocyte percentages decreased on days 1 and 3. Presepsin and procalcitonin had a low positive correlation with CD14 expression and a strong negative correlation with human leukocyte antigen-DR+ monocyte percentages on day 1.Conclusions: Plasma presepsin concentrations are independent prognostic factors for out-of-hospital cardiac arrest patients after return of spontaneous circulation and are correlated with abnormal CD14 and human leukocyte antigen-DR expression on monocytes. Monitoring presepsin levels may be helpful for evaluating the prognosis and impaired innate immune response in the early period after return of spontaneous circulation. [ABSTRACT FROM AUTHOR]

Aim: Whether regulatory T cells (Tregs) are involved in immune disorders of out-of-hospital cardiac arrest (OHCA) patients after return of spontaneous circulation (ROSC) is still unknown. We aimed to observe the expression of circulatory Tregs in OHCA patients and investigate programmed cell death-1 (PD-1) and human leucocyte antigen-DR (HLA-DR) on Tregs to evaluate the induction and activity of Tregs.Methods: Sixty-seven consecutive OHCA patients who recovered from spontaneous circulation over 12 h were enrolled. Clinical and 28-day outcome data were collected. Peripheral blood samples collected on days 1 and 3 after ROSC were analysed to evaluate PD-1 and HLA-DR expression on Tregs. Fifty healthy individuals were enrolled as healthy controls.Results: Compared with those in healthy individuals, circulatory Treg counts significantly decreased without changes of Treg/cluster-of-differentiation (CD)4+ lymphocyte ratios on day 1 after ROSC, and the percentage of PD-1+ Tregs and HLA-DR+ Tregs significantly rose. On day 3, Treg/CD4+ lymphocyte ratios rose with persistently low Treg counts, and the expression of PD-1 and HLA-DR on Tregs was not different from that on day 1. On day 1, both circulatory Treg counts and Treg/CD4+ lymphocyte ratios in non-survivors were lower than those in survivors, and Treg/CD4+ lymphocyte ratios increased in non-survivors on day 3. No significant difference of PD-1 and HLA-DR expression on Tregs was found between survivors and non-survivors on day 1.Conclusions: After ROSC, despite decreased circulatory Treg counts, a relative increase of Treg percentage and enhanced activity of Tregs are involved in early immune regulation of OHCA patients. [ABSTRACT FROM AUTHOR]

Objectives: Postresuscitation care bundle treatment after return of spontaneous circulation in patients experiencing in-hospital cardiac arrest can improve patients' survival and quality of life. The aim of the study was to evaluate the efficacy and safety of combined therapy of Shenfu injection and postresuscitation care bundle in these patients.Design: Prospective, randomized, controlled clinical study.Setting: Fifty hospitals in China.Patients: Adult patients had experienced in-hospital cardiac arrest between 2012 and 2015.Interventions: Based on the standardized postresuscitation care bundle treatment, patients were randomized to a Shenfu injection group (Shenfu injection + postresuscitation care bundle) or control group (postresuscitation care bundle) for 14 days or until hospital discharge. In the Shenfu injection group, 100 mL Shenfu injection was additionally administered via continuous IV infusion, bid.Measurements and Main Results: The primary outcome was 28-day survival after randomization. The secondary outcomes included 90-day survival as well as the duration of mechanical ventilation and the hospital stay and the total cost of hospitalization. Of 1,022 patients enrolled, a total of 978 patients were allocated to the two groups: the control (n = 486) and Shenfu injection (n = 492) groups. The Shenfu injection group had a significantly greater 28-day survival rate (42.7%) than the control group (30.1%). Also, the Shenfu injection group had a significantly higher survival rate at 90 days (39.6%) than the control group (25.9%). Compared with patients in the control group, patients in the Shenfu injection group had lower risks of 28-day mortality (hazard ratio, 0.61; 95% CI, 0.43-0.89; p = 0.009) and 90-day mortality (hazard ratio, 0.55; 95% CI, 0.38-0.79; p = 0.002). In the Shenfu injection group, the duration of mechanical ventilation (8.6 ± 3.2 vs 12.7 ± 7.9 d; p < 0.001) and the hospital stay (8.7 ± 5.9 vs 13.2 ± 8.1 d; p < 0.001) were significantly less than in the control group. Irreversible brain damage was the main cause of death in both groups. No serious drug-related adverse event was recorded.Conclusions: This study demonstrates that Shenfu injection in combination with conventional postresuscitation care bundle treatment is effective at improving clinical outcomes in patients with return of spontaneous circulation after in-hospital cardiac arrest. [ABSTRACT FROM AUTHOR]