Cardiac Arrest Cardiopulmonary Resuscitation Research Articles

The ACE2/Ang-(1-7)/MasR axis alleviates brain injury after cardiopulmonary resuscitation in rabbits by activating PI3K/Akt signaling.

Death among resuscitated patients is mainly caused by brain injury after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The angiotensin converting enzyme 2 (ACE2)/angiotensin (Ang)-(1-7)/Mas receptor (MasR) axis has beneficial effects on brain injury. Therefore, we examined the roles of the ACE2/Ang-(1-7)/MasR axis in brain injury after CA/CPR. We used a total of 76 male New Zealand rabbits, among which 10 rabbits underwent sham operation and 66 rabbits received CA/CPR. Neurological functions were determined by assessing serum levels of neuron-specific enolase and S100 calcium-binding protein B and neurological deficit scores. Brain water content was estimated. Neuronal apoptosis in the hippocampus was assessed by terminal deoxynucleotidyl transferase dUTP nick end labeling assays. The expression levels of various genes were measured by enzyme-linked immunosorbent assay and western blotting. Ang-(1-7) (MasR activator) alleviated CA/CPR-induced neurological deficits, brain edema, and neuronal damage, and A779 (MasR antagonist) had the opposite functions. The stimulation of ACE2/Ang-(1-7)/MasR inactivated the ACE/Ang II/AT1R axis and activated PI3K/Akt signaling. Inhibiting PI3K/Akt signaling inhibited Ang-(1-7)-mediated protection against brain damage after CA/CPR. Collectively, the ACE2/Ang-(1-7)/MasR axis alleviates CA/CPR-induced brain injury through attenuating hippocampal neuronal apoptosis by activating PI3K/Akt signaling.

TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.

Excitotoxicity and the concurrent loss of inhibition are well-defined mechanisms driving acute elevation in excitatory/inhibitory (E/I) balance and neuronal cell death following an ischemic insult to the brain. Despite the high prevalence of long-term disability in survivors of global cerebral ischemia (GCI) as a consequence of cardiac arrest, it remains unclear whether E/I imbalance persists beyond the acute phase and negatively affects functional recovery. We previously demonstrated sustained impairment of long-term potentiation (LTP) in hippocampal CA1 neurons correlating with deficits in learning and memory tasks in a murine model of cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Here, we use CA/CPR and an in vitro ischemia model to elucidate mechanisms by which E/I imbalance contributes to ongoing hippocampal dysfunction in male mice. We reveal increased postsynaptic GABAA receptor (GABAAR) clustering and function in the CA1 region of the hippocampus that reduces the E/I ratio. Importantly, reduced GABAAR clustering observed in the first 24 h rebounds to an elevation of GABAergic clustering by 3 d postischemia. This increase in GABAergic inhibition required activation of the Ca2+-permeable ion channel transient receptor potential melastatin-2 (TRPM2), previously implicated in persistent LTP and memory deficits following CA/CPR. Furthermore, we find Ca2+-signaling, likely downstream of TRPM2 activation, upregulates Ca2+/calmodulin-dependent protein kinase II (CaMKII) activity, thereby driving the elevation of postsynaptic inhibitory function. Thus, we propose a novel mechanism by which inhibitory synaptic strength is upregulated in the context of ischemia and identify TRPM2 and CaMKII as potential pharmacological targets to restore perturbed synaptic plasticity and ameliorate cognitive function.

Abstract 13334: Safety of Chest Compressions in Patients With a Durable Left Ventricular Assist Device

Introduction: The safety of chest compressions (CC) during cardiopulmonary resuscitation (CPR) among pts with a durable left ventricular assist device (LVAD) is an area of controversy. Concerns regarding device malfunction or dislodgment with CC may result in significant delays or the withholding of life-sustaining intervention entirely. Current societal guidelines, based on small case reports, suggest that manual CC are probably not harmful, but offer no additional guidance. Furthermore, they acknowledge that there are no data regarding the use of machine-assisted CC. Methods: We retrospectively reviewed medical records of consecutive pts who underwent durable LVAD implantation at Duke University from 2013-2022. Charts were searched for “code”, “arrest”, “compressions”, and “rapid response team” to identify all instances of cardiac arrest (CA). Baseline pt characteristics, details of the arrest (including CC details), in-hospital care processes, and pt outcomes were abstracted. Results: Of 750 pts reviewed, 58 (mean age 64 years, 76% male, median LVAD support duration 19 months) had documented CA. Fifteen (26%) pts presented with an out-of-hospital CA. Twenty-four (41%) pts did not receive CC. The most commonly reported reason for avoiding CC was “LVAD in place - contraindicated.” The CPR duration was longer among those who received CC (median 30mins, range: 1-120 mins) than those who did not (median 20 mins, range: 2-79 mins). Two pts had support from a Lund University Cardiac Assist System (LUCAS) device. Among those who survived either manual and machine-assisted CC, 27% had a post-arrest TTE and none showed evidence of LVAD malfunction/dislodgment. Conclusions: Among pts with a durable LVAD who underwent CPR for CA we found no evidence of device dislodgment or safety concerns associated with either manual or LUCAS-assisted CPR. Future multicenter and prospective evaluation is necessary to both confirm these findings and to inform the guidelines.

16 Does Point-of-care Ultrasound Improve Survivability During Cardiopulmonary Resuscitation in Cardiac Arrest? A Systematic Review and Meta-analyses

16 Does Point-of-care Ultrasound Improve Survivability During Cardiopulmonary Resuscitation in Cardiac Arrest? A Systematic Review and Meta-analyses

Moderate Hyperkalemia Regulates Autophagy to Reduce Cerebral Ischemia-Reperfusion Injury in a CA/CPR Rat Model.

Cerebral ischemia-reperfusion injury (CIRI) can cause irreversible brain damage and autophagy has been implicated in the pathophysiology. Increasing serum potassium (K+) levels reduces CIRI, but the relationship between its protective mechanism and autophagy is unclear. In this study, we aimed to find the optimal degree of raising serum (K+) and to investigate the relationship between high (K+) and autophagy and the underlying mechanisms in a cardiac arrest/cardiopulmonary resuscitation (CA/CPR) rat model. Sprague Dawley (SD) rats were divided into four groups: S group, N group, P group, and Q group. The rats S group and N group were administered saline. The rats P group and Q group were administered 640 mg/kg of potassium chloride (KCl) continuously pumped at 4 mL/h (21.3 mg/(kg·min) and divided according to the electrocardiogram (ECG) changes during the administration of KCl. After 24-h of resuscitation, neural damage was assessed by measuring neurological deficit score (NDS), oxidative stress markers, and pathological staining of the cerebral cortex. The level of autophagy and the expression of mTOR-ULK1-Beclin1 pathway-related proteins were evaluated using transmission electron microscopy (TEM), immunostaining, and western blotting. Our results revealed that high (K+) improved NDS and decreased the oxidative stress markers. The autophagosomes, autolysosomes, and lysosomes were decreased following treatment KCl. Furthermore, the levels of micro-tubule-associated protein 1 light chain 3 (LC3) Ⅱ/Ⅰ, Unc-51-like kinase 1 (ULK1), and Beclin1 were decreased, whereas mTOR expression was increased in the cortex. The results demonstrated that moderate hyperkalemia could alleviate autophagy after CIRI via regulating the mTOR-ULK1-Beclin1 pathway.

Alterations of the gut microbial community structure modulates the Th17 cells response in a rat model of asphyxial cardiac arrest

Th17 cells triggered inflammation is a critical element in cerebral ischemic injury, and the gut microbiota intricately impacts T lymphocytes. Nevertheless, it remains unclear whether the gut microbiota involves in cardiac arrest/cardiopulmonary resuscitation (CA/CPR) induced-brain injury through Th17 cells. The present study investigated the interaction between gut microbiota and Th17 cells in a rat model. We observed that CA/CPR induced the alterations of the gut microbial community structure, and elevated the level of IL-17 in the serum, and a slight infiltration of Th17 cells into the brain. The Th17 cells were increased significantly in the peripheral blood, 28.33 ± 6.18% of these Th17 cells were derived from the Peyer’s patches of small intestine. Furthermore, fecal microbiota transplantation (FMT) from rats with CA/CPR induced Th17 cell response, promoting hippocampal cell apoptosis and declining learning ability and memory in recipient rats. Taken together, CA/CPR-induced alterations of the gut microbial community structure stimulated Th17 cell response which aggravated brain injury.

Video laryngoscopy and direct laryngoscopy for cardiac arrest: A meta-analysis of clinical studies and trials

BackgroundIntubation is an essential procedure in cardiopulmonary resuscitation (CPR). We conducted a systematic review and meta-analysis of trials and studies comparing the performance of video laryngoscope (VL) and direct laryngoscope (DL) in endotracheal intubation (ETI) during CPR in cardiac arrest (OHCA) patients. MethodsWe searched the PUBMED, EMBASE, and Cochrane library databases. We analyzed the first-pass success rate, total intubation time, Cormack–Lehane grade (CL grade), esophageal intubation rate, and dental injury rate among the in-hospital cardiac arrest (IHCA) patients or out-of-hospital cardiac arrest (OHCA) patients. We demonstrated the pooled results of continuous outcomes by mean difference (MD) and dichotomous outcomes by odds ratio (OR), with a 95% confidence interval (CI) using a random-effects model. ResultsWe obtained six observational studies and one randomized control trial. The pooled results showed a significant increase in first-pass success rate (OR: 1.86, 95% CI: 1.41, 2.47), Cormack–Lehane (CL) grade (OR: 2.01, 95% CI: 1.59,2.53), and a decrease of esophageal intubation rate (OR: 0.25, 95% CI: 0.08, 0.85) in the VL group compared with DL group. Also, a non-significant decrease in dental injury rate [OR: 0.23, 95% CI: 0.05, 1.08) was observed in the VL group compared with the DL group. There was no statistical difference between the VL and DL groups, although the VL group seemed to have a shorter total intubation time (MD: -15.43, 95% CI: −34.67, 3.81). Types of laryngoscopes were not associated with the rate of ROSC [OR 1.01 (0.95,1.07); P = 0.83]. No differences in survival outcomes were observed between the two approaches. ConclusionsCompared to DL, VL was found to be associated with first-pass success and CL grade. We recommend prioritizing VL over DL when performing ETIs for patients with cardiac arrest.

Inhibition of ERK downregulates autophagy via mitigating mitochondrial fragmentation to protect SH-SY5Y cells from OGD/R injury

BackgroundCerebral ischemia-reperfusion injury (CIRI) is the main cause leading to high mortality and neurological disability in patients with cardiac arrest/cardiopulmonary resuscitation (CA/CPR). Our previous study found that extracellular signal-regulated kinase (ERK) activation, dynamin-related protein1 (Drp1)/Mitofusin2 (Mfn2)-dependent mitochondrial dynamics imbalance, and excessive autophagy were involved in the mechanism of nerve injury after CA/CPR. However, the specific pathological signaling pathway is still unknown. This study aimed to explore the molecular function changes of ERK-Drp1/Mfn2-autophagy signaling pathway in SH-SY5Y cell oxygen-glucose deprivation/reoxygenation (OGD/R) model, to further clarify the pathophysiological mechanism of CIRI, and to provide a new strategy for cerebral protection after CIRI.MethodsSH-SY5Y cells were pretreated with drugs 24 h before OGD/R. The Drp1 and Mfn2 knockdown were adopted small interfering RNAs. The overexpression of p-Drp1S616 and Mfn2 were used recombinant plasmids. The expression levels of mitochondrial dynamics proteins (p-Drp1, Drp1, Mfn2, Mfn1 and Opa1) and autophagy markers (LC3, Beclin1 and p62) were measured with the Western blotting. The mRNA levels after transfection were determined by PCR. Cell injury and viability were evaluated with released LDH activity and CCK8 assay kits. Mitochondria morphology and autophagosome were observed under transmission electron microscopy. Mitochondrial function was detected by the mitochondrial permeability transition pore assay kit. The co-expression of p-ERK, p-Drp1 and LC3 was assessed with multiple immunofluorescences. One-way analysis of variance followed by least significance difference post hoc analysis (for equal homogeneity) or Dunnett’s T3 test (for unequal homogeneity) were used for statistical tests.ResultsERK inhibitor-PD98059 (PD) protects SH-SY5Y cells from OGD/R-induced injury; while ERK activator-TPA had the opposite effect. Similar to autophagy inhibitor 3-MA, PD downregulated autophagy to improve cell viability; while autophagy activator-rapamycin further aggravated cell death. PD and Drp1-knockdown synergistically attenuated OGD/R-induced Drp1 activation, mPTP opening and cell injury; overexpression of Drp1S616E or ablating Mfn2 partly abolished the protective effects of PD. Multiple immunofluorescences showed that p-ERK, p-Drp1 and LC3 were co-expressed.ConclusionInhibition of ERK downregulates autophagy via reducing Drp1/Mfn2-dependent mitochondrial fragmentation to antagonize mitochondrial dysfunction and promotes cell survival in the SH-SY5Y cells OGD/R model.9RDMMKPHSZ2No4hHf87VtDVideo

The efficacy of venous-arterial membrane oxygenation for emergency extracorporeal life support: results from a single-center large series over 6 years.

The efficacy of venous-arterial extracorporeal membrane oxygenation (VA-ECMO) in supporting cardio-pulmonary resuscitation for cardiac arrest is still debated. This study aimed to evaluate the outcome of patients treated with VA-ECMO positioned according to different clinical indications. The method is retrospective data analysis from patients admitted to a tertiary referral center for VA-ECMO in 6 years. The study population was divided into three groups based on the VA-ECMO indication: patients with refractory cardiac arrest (CA group), cardiogenic shock after return of spontaneous circulation (CS-ROSC group), and cardiogenic shock without cardiac arrest (CS group). Seventy-nine patients underwent emergency VA-ECMO, 49 patients (62.0%) were in the CA group, 14 (17.7%) in the CS-ROSC group, and 16 patients (20.3%) in the CS group. The overall survival at 28 days was different between the three groups (6.1% in the CA group, 64.2% in the CS-ROSC group, and 50.0% in the CS group, p < 0.001) and remained significant at 12months (p < 0.001). Furthermore, the Cerebral Performance Category at 12months differed between groups with good outcomes in 4.1% of patients in CA, 50.0% in CS-ROSC, and 31.2% in CS groups (p < 0.001). In the studied population, emergency VA-ECMO had negligible efficacy in refractory cardiac arrest, while it was correlated with a good outcome in cardiogenic shock after cardiac arrest, such as in cardiogenic shock alone. Patients with ROSC appear to benefit from VA-ECMO in the setting of persistent shock at rates comparable to cardiogenic shock patients who never sustained cardiac arrest.

A Nanotherapy of Octanoic Acid Ameliorates Cardiac Arrest/Cardiopulmonary Resuscitation-Induced Brain Injury via RVG29- and Neutrophil Membrane-Mediated Injury Relay Targeting.

Treatment of cardiac arrest/cardiopulmonary resuscitation (CA/CPR)-induced brain injury remains a challenging issue without viable therapeutic options. Octanoic acid (OA), a lipid oil that is mainly metabolized in the astrocytes of the brain, is a promising treatment for this type of injury owing to its potential functions against oxidative stress, apoptosis, inflammation, and ability to stabilize mitochondria. However, the application of OA is strictly limited by its short half-life and low available concentration in the target organ. Herein, based on our previous research, an OA-based nanotherapy coated with a neutrophil membrane highly expressing RVG29, RVG29-H-NPOA, was successfully constructed by computer simulation-guided supramolecular assembly of polyethylenimine and OA. The in vitro and in vivo experiments showed that RVG29-H-NPOA could target and be distributed in the injured brain focus via the relay-targeted delivery mediated by RVG29-induced blood-brain barrier (BBB) penetration and neutrophil membrane protein-induced BBB binding and injury targeting. This results in enhancements of the antioxidant, antiapoptotic, mitochondrial stability-promoting and anti-inflammatory effects of OA and exhibited systematic alleviation of astrocyte injury, neuronal damage, and inflammatory response in the brain. Due to their systematic intervention in multiple pathological processes, RVG29-H-NPOA significantly increased the 24 h survival rate of CA/CPR model rats from 40% to 100% and significantly improved their neurological functions. Thus, RVG29-H-NPOA are expected to be a promising therapeutic for the treatment of CA/CPR-induced brain injury.

Clinical practice of emergency department-initiated extracorporeal cardiopulmonary resuscitation for cardiac arrest in adults.

Clinical practice of emergency department-initiated extracorporeal cardiopulmonary resuscitation for cardiac arrest in adults.

Role of caspase-8 in stem cell transplantation alleviates rat cerebral cortex apoptosis after cardiopulmonary resuscitation

To explore the effects and the possible mechanism of bone marrow mesenchymal stem cell (BMMSC) transplantation on apoptosis in rats cerebral cortex after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The BMMSC of 2 Sprague-Dawley (SD) rats aged 4-5weeks was extracted, and the 3rd passage was used in experimental study. Eighteen Sprague-Dawley (SD) rats were divided into sham group, model group (CA/CPR group) and intervention group (BMMSC group) according to random number table method, with 6 rats in each group. CPR was performed 6 minutes after asphyxia induced CA. In sham group, CA was not induced except performing general surgical procedure. At 1 hour after return of spontaneous circulation (ROSC), 0.5 mL phosphate buffered saline (PBS) was injected through tail vein in CA/CPR group. 2×109/L green fluorescence protein (GFP)-labeled BMMSC was injected through tail vein 1 hour after ROSC in BMMSC group. Neurological deficit score (NDS) were assessed in every group at 72 hours after CPR. Serum S100 calcium binding protein B (S100B) levels were assayed by enzyme linked immunosorbent assay (ELISA). Distribution of BMMSC in brain was observed under a fluorescent microscope. Apoptosis rate in cerebral cortex was assayed by TdT-mediated dUTP nick-end labeling (TUNEL). Western blotting was performed to measure the expression levels of active aspartic acid specific cysteine proteinase (caspase-8 and caspase-9) in cerebral cortex. At 3 days after CPR, compared with sham group, the apoptosis of cerebral cortex cells was increased and brain damage was obvious, NDS score was decreased significantly (56.6±5.5 vs. 80.0±0.0, P < 0.05), and serum S100B was increased markedly (ng/L: 45.1±4.7 vs. 19.1±1.4, P < 0.05), apoptosis rate of cerebral cortex cells increased significantly [(52.9±11.8)% vs. (10.1±1.5)%, P < 0.05], the level of active caspase-8 expression in cerebral cortex was significantly higher (caspase-8/GAPDH: 0.689±0.047 vs. 0.330±0.108, P < 0.05), and there was no significant difference in active caspase-9 protein expression (caspase-9/GAPDH: 0.428±0.014 vs. 0.426±0.021, P > 0.05) in CA/CPR group. After BMMSC transplantation, GFP-labeled BMMSC were primarily detected in cerebral cortex, compared with CA/CPR group, the apoptosis of cerebral cortex cells and brain injury were significantly improved in BMMSC group, NDS score increased significantly (70.6±2.1 vs. 56.6±5.5, P < 0.05), serum S100B levels in BMMSC group were lower (ng/L: 32.0±3.2 vs. 45.1±4.7, P < 0.05), apoptosis rate of cerebral cortex cells decreased significantly [(31.1±3.4)% vs. (52.9±11.8)%, P < 0.05], and the active caspase-8 expression in cerebral cortex in BMMSC group was significantly decreased (caspase-8/GAPDH: 0.427±0.067 vs. 0.689±0.047, P < 0.05). The active caspase-9 expression in cerebral cortex in BMMSC group and CA/CPR group were not significantly different (caspase-9/GAPDH: 0.431±0.022 vs. 0.428±0.014, P > 0.05). BMMSC transplantation can alleviate rat brain damage after CA/CPR possibly by inhibiting the death receptor mediated apoptotic pathway to inhibit the apoptosis of brain cells.

Abstract 285: Traditional Cardiopulmonary Resuscitation In Cardiac Arrest For Patients On Venovenous Extracorporeal Membrane Oxygenation

Introduction: Mortality for patients on VV-ECMO remains high despite increased use during the COVID-19 pandemic. Unlike VA-ECMO which provides life support for cardiac failure and can be used as a bridge to definitive therapy during cardiac arrest (e-CPR), patients who arrest while on VV-ECMO currently may undergo traditional cardiopulmonary resuscitation (CPR). This poses many challenges such as potential cannula position disruption of the VV-ECMO system during compressions and it is unclear if patients on VV-ECMO will benefit from being offered traditional CPR. Hypothesis: Traditional CPR is effective in patients who arrest while on VV-ECMO. Methods: A retrospective chart review of inpatient cardiac arrest data from a high-volume ECMO center was performed. Patients who arrested while on VV-ECMO were included. Data including demographics, etiology of arrest, return of spontaneous circulation (ROSC) and survival to discharge were reviewed. Survival data was compared with the ECLS International Summary of Statistics. Results: We identified 19 patients on VV-ECMO who underwent CPR for cardiac arrest between September 2012 and November 2021. The average age of the patients was 42.7 years and 89.5% (n=17) were men. Seven of the nineteen total patients (36.8%) were being treated for ARDS from COVID-19 pneumonia. The arrest occurred on average 35.6 days into hospitalization (range: 1-132 days). The initial rhythm was pulseless electrical activity in 13 patients (68.4%), and the etiologies of arrest included hypoxemia (n=10, 52.6%), ECMO machine failure or during oxygenator exchange (n=3, 15.8%), pneumothorax (n=2, 10.5%), and cardiac tamponade (n=1, 5.3%). ROSC occurred in all 19 patients (100%), however only 4 patients (21.1%) survived to discharge with good neurologic recovery. Survival to discharge for all-comers on VV-ECMO is 66%. Conclusions: While there is limited evidence for the effectiveness of traditional CPR for patients on VV-ECMO, in this sample, ROSC was universal and one-fifth of patients survived to discharge. Future studies should continue to study the utility of CPR on VV-ECMO and how to optimize technique to improve outcomes for these critically-ill patients.

Effect of extracellular signal-regulated kinase inhibitor on calpain in rat cerebral cortex after cardiopulmonary resuscitation

To explore the effect of extracellular signal-regulated kinase (ERK) inhibitor PD98059 on calpain-related proteins in the brain, and to understand the pathophysiological changes of calpain in cerebral ischemia/reperfusion injury (CIRI). Forty-two rats were divided into sham operation (Sham) group (n = 6), model group (n = 12), dimethyl sulfoxide (DMSO) control group (n = 12), and PD98059 group (n = 12) by random number table. The rat model of CIRI induced by cardiac arrest-cardiopulmonary resuscitation (CA-CPR) was reproduced by transesophageal electrical stimulation to induce ventricular fibrillation. In the Sham group, only the basic operations such as anesthesia, tracheal intubation, and arteriovenous catheterization were performed without CA-CPR. The rats in the DMSO control group and PD98059 group were injected with DMSO or PD98059 0.30 mg/kg via femoral vein, respectively, 30 minutes after the restoration of spontaneous circulation (ROSC), and rats in the Sham group and model group were given the same amount of normal saline. The duration of CPR, 24-hour survival rate and neurological deficit score (NDS) after ROSC were recorded. Hematoxylin-eosin (HE) staining and Nissl staining were used to observe the pathological changes of the cerebral cortex. The expressions of phosphorylated ERK (p-ERK), ERK, calpastatin, calpain-1, and calpain-2 were detected by Western blotting. The co-expression of p-ERK and calpain-2 was detected by double immunofluorescence. There were no significant differences in the duration of CPR and 24-hour survival rate among all groups. In the model group, the nuclei of the cerebral cortex were obviously deformed and pyknotic, cells vacuoles and tissues were arranged disorderly, Nissl corpuscles were significantly reduced, NDS scores were also significantly reduced, level of ERK phosphorylation was increased, and calpain-2 protein was significantly up-regulated compared with the Sham group. There was no significant difference in the above parameters between the DMSO control group and the model group. After intervention with PD98059, the pathological injury of brain tissue was significantly improved, Nissl corpuscles were significantly increased, the NDS score was significantly higher than that in the model group [75.0 (72.0, 78.0) vs. 70.0 (65.0, 72.0), P < 0.05], the level of ERK phosphorylation and calpain-2 protein expression were significantly lower than those in the model group [p-ERK (p-ERK/ERK): 0.65±0.12 vs. 0.92±0.05, calpain-2 protein (calpain-2/GAPDH): 0.73±0.10 vs. 1.07±0.14, both P < 0.05], while there was no significant difference in the expressions of calpastatin and calpain-1 in the cerebral cortex among all the groups. Double immunofluorescence staining showed that p-ERK and calpain-2 were co-expressed in cytosol and nucleus, and the co-expression rate of p-ERK and calpain-2 in the model group was significantly higher than that in the Sham group [(38.6±4.3)% vs. (9.2±3.5)%, P < 0.05], while it was significantly lowered in the PD98059 group compared with the model group [(18.2±7.0)% vs. (38.6±4.3)%, P < 0.05]. ERK together with calpain-2 participated in CIRI induced by CA-CPR. PD98059 inhibited the expression of calpain-2 and ERK phosphorylation. Therefore, ERK/calpain-2 may be a novel therapeutic target for CIRI.

Inhibition of extracellular signal-regulated kinase downregulates endoplasmic reticulum stress-induced apoptosis and decreases brain injury in a cardiac arrest rat model.

Cerebral ischemia-reperfusion injury (CIRI) is the predominant cause of neurological disability after cardiac arrest/cardiopulmonary resuscitation (CA/CPR). The endoplasmic reticulum stress (ERs)-induced apoptosis plays an important role in neuronal survival/death in CIRI. Our previous studies reported that the extracellular signal-regulated kinase (ERK) inhibitor, PD98059, alleviates CIRI after CA/CPR. Whether ERs-induced apoptosis is involved in the neuroprotection of PD98059 remains unknown. This study aims to investigate the effects of ERK inhibition by PD98059 on ERs-induced apoptosis after CIRI in the CA/CPR rat model. The baseline characteristics of male adult Sprague-Dawley (SD) rats in all groups were evaluated before CA/CPR. The SD rats that survived from CA/CPR were randomly divided into 3 groups (n=12/group): normal saline group (1 ml/kg), dimethylsulfoxide (DMSO, the solvent of PD98059, 1 ml/kg) group, PD98059 group (0.3 mg/kg). Another 12 SD rats were randomly selected as the Sham group. Twenty-four hours after resuscitation, neural injury was assessed by survival rate, neurological deficit scores (NDS) and Nissl staining; apoptosis of brain cells was detected using terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining; mRNA expression and protein levels of ERs-related protein BIP, PERK, ATF4 and CHOP were checked with RT-PCR and Western Blot. The results showed that there were no significant differences in baseline characteristics before CA/CPR among all groups. PD98059 significantly improved survival rate and NDS, increased the Nissl bodies in neurons, reduced apoptosis, downregulated the mRNA transcription and expression levels of BIP, PERK, ATF4 and CHOP at 24 h after CA/CPR. Our results demonstrate that inhibition of ERK by PD98059 alleviates ERs-induced apoptosis via BIP-PERK-ATF4-CHOP signaling pathway and mitigates CIRI in the CA/CPR rat model.

Impella CP implantation during cardiopulmonary resuscitation for cardiac arrest: a multicenter experience

Abstract Funding Acknowledgements Type of funding sources: None. Abstract: Background Impella CP is a left ventricular pump which may serve as a circulatory support during cardiopulmonary resuscitation (CPR) for cardiac arrest (CA). Nevertheless, the survival rate and factors associated with survival in patients undergoing Impella insertion during CPR for CA are unknown. Methods We performed a retrospective multicenter international registry of patients undergoing Impella insertion during on-going CPR for in- or out-of-hospital CA. We recorded immediate and 30-day survival with and without neurologic impairment using the cerebral performance category score and evaluated the factors associated with survival. Results Thirty-five patients had an Impella CP implanted during CPR for CA. Refractory ventricular arrhythmias were the most frequent initial rhythm (65.7%). In total, 65.7% of patients immediately survived. At 30 days, 45.7% of patients were still alive. The 30-day survival rate without neurological impairment was 37.1%. In univariate analysis, survival was associated with both an age &amp;lt; 75 years and a time from arrest to CPR ≤ 5 min (p = 0.035 and p = 0.008, respectively). Conclusions In our multicenter registry, Impella CP insertion during ongoing CPR for CA was associated with a 37.1% rate of 30-day survival without neurological impairment. The factors associated with survival were a young age and a time from arrest to CPR ≤ 5 min.

Survival and factors associated with survival with extracorporeal life support during cardiac arrest: a systematic review and meta-analysis

Abstract Funding Acknowledgements Type of funding sources: None. Background Survival after sudden cardiac arrest (CA) remains low at approximately 10% despite recent advances in cardiopulmonary resuscitation (CPR). Extracorporeal life support (ECLS) may be useful to improve outcomes. However, it is resource intensive and associated with significant complications. We therefore performed a meta-analysis of all available observational studies of patients receiving ECLS-facilitated CPR to estimate the overall survival rate to discharge and predictors of survival. Methods We conducted a literature search in MEDLINE, PubMed EMBASE and the Cochrane Library from inception to September 2020. Studies were included if they focused on ECLS during CPR for CA in adult patients and provided survival data. Results Among the 1745 articles identified by our search, 81 studies involving 9256 patients were included in the analysis. Overall, the pooled estimated survival was 26.2% at discharge and 20.4% with a good neurological outcome. The heterogeneity across studies was significant for both outcomes. Meta-regressions found a significant association between survival at discharge and lower lactate values (b=-0.1, 95% CI [-0.2; -0.05], p=0.002), intrahospital CA (b= 0.005, 95% CI [0.002; 0.008], p= 0.002), and lower CPR duration (b=-0.009, 95% CI [-0.02; -0.002], p=0.02). After adjustment for age, intrahospital CA, and mean CPR duration, an initial shockable rhythm was the only independent factor associated with survival to discharge (b=0.02, 95% CI [0.007; 0.02], p=0.0004). Conclusion The overall survival rate on discharge of ECLS-facilitated CPR for CA was 26.2%, and the survival with good neurological outcome was 20.4%. An initial shockable rhythm was the only independent predictor of survival to discharge.

Chest Compression Fraction Alone Does Not Adequately Measure Cardiopulmonary Resuscitation Quality in Out-of-Hospital Cardiac Arrest.

High-quality cardiopulmonary resuscitation in out-of-hospital cardiac arrest is important for increased survival and improved neurological outcome. Chest compression fraction measures the proportion of time chest compressions are given during a cardiac arrest resuscitation. Chest compression fraction has not been compared with the quality of chest compressions delivered at the recommended rate and depth of 100-120/min and 2.0-2.4 inches, respectively. We evaluate whether chest compression fraction correlates with compressions at a target rate of 100-120/min and depth of 2.0-2.4 inches in chest diameter. A prospective, observational study design was used to compare chest compression fraction to compressions in target in out-of-hospital cardiac arrest patients in a prehospital urban setting. We include all adult, non-traumatic out-of-hospital cardiac arrest patients with a resuscitation attempt during January 1, 2019 through September 30, 2019, for a total of 9 months. Spearman's rank correlation was used to determine correlation between compression fraction and compressions in target. A total of 120 out-of-hospital cardiac arrest cases were included in the study. We found a high chest compression fraction median of 83% (interquartile range 72-90%), but a low compression in target median of 13% (interquartile range 5-29%). There was no significant correlation between chest compression fraction and compressions in target when analyzed linearly (Spearman's Rho=0.165, p=0.072). No difference was found when dichotomizing chest compression fraction into high and low variables in comparison with compressions in target (14% vs. 10%, p=0.119). Chest compression fraction is not associated with compressions in target for rate and depth for out-of-hospital cardiac arrest cardiopulmonary resuscitation.

Clinical Significance of Gray to White Matter Ratio after Cardiopulmonary Resuscitation in Children.

Cardiopulmonary resuscitation (CPR) successfully restores systemic circulation approximately 50% of the time; however, many successfully restored patients have severe neurologic damage. In adults, the gray matter to white matter attenuation ratio (GWR) in brain computed tomography (CT) correlates with the neurologic outcome. However, in children, the clinical significance of GWR still remains unclear. The aim of this study was to evaluate the clinical characteristics of children who underwent CPR for cardiac arrest according to the survival and to demonstrate the differentiation of grey/white matter by Hounsfield units of brain CT and to characterize the attenuations of grey and white matters. Methods: This is a retrospective single-center study. We enrolled those who underwent brain CT within 24 h after return of spontaneous circulation (ROSC) from January 2005 to June 2018. Brain CTs were taken within 24 h of ROSC. We measured the attenuation of grey and white matter in Hounsfield units and calculated GWR. They were compared with healthy controls. Patients were analyzed as follows: survivors vs. non-survivors and better neurologic outcome vs. worse neurologic outcome. Results: Among 100 pediatric patients who had CPR, 56 met inclusion criteria. There were 24 patients who survived and 32 non-survivors. Our study revealed that the incidence of seizure, duration of CPR, and instances of hypothermia were significantly different between survivors and non-survivors. In both survivors and non-survivors, the attenuation of the caudate nucleus, putamen, GWR-basal ganglia, and average GWR were significantly different from controls. In regression analyses, the medial cortex and average GWR were the significant variables to predict survival, and the receiver operating curves revealed areas under curve of 0.733 and 0.666, respectively. Also, the medial cortex 1 was the only variable that predicted the neurologic outcome. Conclusions: There was some predictive survival value of GWR and medial cortex at the centrum semiovale level in early brain CT within 24 h after cardiac arrest. Although we could not find the predictive value of GWR in the neurologic outcome of pediatric patients, we found that the absolute attenuation of the medial cortex was low in patients with worse neurologic outcomes. Further prospective, multicenter studies are needed to determine the predictive value of GWR and the medial cortex.

Survival and Factors Associated with Survival with Extracorporeal Life Support During Cardiac Arrest: A Systematic Review and Meta-Analysis

The survival rate after cardiac arrest (CA) remains low. The utilization of extracorporeal life support is proposed to improve management. However, this resource-intensive tool is associated with complications and must be used in selected patients. We performed a meta-analysis to determine predictive factors of survival. Among the 81 studies included, involving 9256 patients, survival was 26.2% at discharge and 20.4% with a good neurologic outcome. Meta-regressions identified an association between survival at discharge and lower lactate values, intrahospital CA, and lower cardio pulmonary resuscitation (CPR) duration. After adjustment for age, intrahospital CA, and mean CPR duration, an initial shockable rhythm was the only remaining factor associated with survival to discharge (β = 0.02, 95% CI: 0.007-0.02; p = 0.0004).