Cardiac Arrest Group Research Articles

Spontaneous Coronary Artery Dissection (SCAD) with cardiac arrest at presentation: a subanalysis from the DISCO registry

Abstract Introduction Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients. Methods The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in-hospital bleeding. Results Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST-segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In-hospital outcomes, except for longer hospitalization, did not differ. On follow-up (average 21 months), MACE rates were similar between groups. Conclusions Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in-hospital and during long-term follow-up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.

Lateral atrial septal defect closure with induced ventricular fibrillation versus cardioplegic arrest.

We present our single-centre results of paediatric patients who underwent surgical atrial septal defect II closure via lateral thoracotomy. Retrospective analysis. Patients were divided into a cardiac arrest group and a cardiac fibrillation group. All procedures were performed via right midaxillary thoracotomy through a single incision without side ports. All 37 consecutive patients between March 2019 and August 2022 (median age 3 years; percentile 25th: 2; 75th: 5 years) in both groups were free of mortality and postoperative morbidity such as haemodynamically relevant residual shunt or malignant arrhythmias. Cardiopulmonary bypass time was significantly shorter in the fibrillation group (mean: 34.7 min vs 52.6 min, P = 0.01), and all patients were weaned off the ventilator immediately postoperatively. Length of the intensive care unit stay was not different between the 2 groups. Postoperative hospital stay was significantly longer in patients with cardiac arrest (mean: 5.6 days vs 4.9 days, P = 0.04). Postoperative laboratory parameters did not differ between the 2 groups. All patients were discharged with normal left ventricular function and normalized cardiac enzymes. Minimally invasive closure of an atrial septal defect during atrial fibrillation is a safe procedure with results comparable to those of an induced cardiac arrest procedure.

Early Prediction of Cardiac Arrest in the Intensive Care Unit Using Explainable Machine Learning: Retrospective Study.

Cardiac arrest (CA) is one of the leading causes of death among patients in the intensive care unit (ICU). Although many CA prediction models with high sensitivity have been developed to anticipate CA, their practical application has been challenging due to a lack of generalization and validation. Additionally, the heterogeneity among patients in different ICU subtypes has not been adequately addressed. This study aims to propose a clinically interpretable ensemble approach for the timely and accurate prediction of CA within 24 hours, regardless of patient heterogeneity, including variations across different populations and ICU subtypes. Additionally, we conducted patient-independent evaluations to emphasize the model's generalization performance and analyzed interpretable results that can be readily adopted by clinicians in real-time. Patients were retrospectively analyzed using data from the Medical Information Mart for Intensive Care-IV (MIMIC-IV) and the eICU-Collaborative Research Database (eICU-CRD). To address the problem of underperformance, we constructed our framework using feature sets based on vital signs, multiresolution statistical analysis, and the Gini index, with a 12-hour window to capture the unique characteristics of CA. We extracted 3 types of features from each database to compare the performance of CA prediction between high-risk patient groups from MIMIC-IV and patients without CA from eICU-CRD. After feature extraction, we developed a tabular network (TabNet) model using feature screening with cost-sensitive learning. To assess real-time CA prediction performance, we used 10-fold leave-one-patient-out cross-validation and a cross-data set method. We evaluated MIMIC-IV and eICU-CRD across different cohort populations and subtypes of ICU within each database. Finally, external validation using the eICU-CRD and MIMIC-IV databases was conducted to assess the model's generalization ability. The decision mask of the proposed method was used to capture the interpretability of the model. The proposed method outperformed conventional approaches across different cohort populations in both MIMIC-IV and eICU-CRD. Additionally, it achieved higher accuracy than baseline models for various ICU subtypes within both databases. The interpretable prediction results can enhance clinicians' understanding of CA prediction by serving as a statistical comparison between non-CA and CA groups. Next, we tested the eICU-CRD and MIMIC-IV data sets using models trained on MIMIC-IV and eICU-CRD, respectively, to evaluate generalization ability. The results demonstrated superior performance compared with baseline models. Our novel framework for learning unique features provides stable predictive power across different ICU environments. Most of the interpretable global information reveals statistical differences between CA and non-CA groups, demonstrating its utility as an indicator for clinical decisions. Consequently, the proposed CA prediction system is a clinically validated algorithm that enables clinicians to intervene early based on CA prediction information and can be applied to clinical trials in digital health.

Intraoperative cardiac arrest in patients undergoing congenital cardiac surgery

ObjectiveTo describe intraoperative cardiac arrest in patients undergoing congenital heart surgery. MethodsThe Society of Thoracic Surgeons Congenital Heart Surgery Database was queried. Predictors of intraoperative cardiac arrest were assessed using univariate and multivariable analyses. The univariate relationship between intraoperative cardiac arrest was also compared with available outcomes in the database. ResultsA total of 92,764 cases had anesthesia adverse event data, and 357 patients (0.38%) had an intraoperative cardiac arrest. Multivariable predictors of an intraoperative cardiac arrest included age (odds ratio [OR], 0.98 per year; 95% confidence interval [CI], 0.97-0.99; P = .036), preoperative cardiac arrest (<48 hours) (OR, 9.6; 95% CI 6.3-14.6, P < .001), preoperative neurologic deficit (OR, 2.0; 95% CI, 1.3-3.1, P < .002), noninsulin-dependent diabetes mellitus (OR, 6.4; 95% CI, 1.9-21.9, P = .003), increasing Society of Thoracic Surgeons-European Association for Cardio-Thoracic Surgery (STAT) category (OR, 2.3 for STAT 5 vs STAT 1; 95% CI, 1.3-3.9, P = .003), urgent (OR, 2.0; 95% CI, 1.6-2.6, P < .001) or emergent surgery (OR, 3.1; 95% CI, 1.9-5.0, P < .001), and increasing length of total operating room time (OR, 1.2 per hour; 95% CI, 1.2-1.3, P < .001). Intraoperative cardiac arrest was associated with a greater 30-day mortality (14.6% vs 1.8%, P < .001). There were more morbidities in the intraoperative cardiac arrest group including postoperative neurologic deficits (12% vs 1.0%, P < .001), multisystem organ failure (5.9% vs 0.7%, P < .001), and greater rates of unplanned reoperation (19.3% vs 5.0%, P < .001) or interventional cardiac catheterization (7% vs 3.2%, P < .001). ConclusionsThe incidence of intraoperative cardiac arrest is low; however, it is an important indicator of significant patient perioperative morbidity and mortality.

The Association between Cardiac Arrest and Mortality in Patients with Acute Myocardial Infarction Complicated by Cardiogenic Shock.

The impact of cardiac arrest (CA) at admission on the prognosis of patients with acute myocardial infarction (AMI) complicated by cardiogenic shock (CS) remains a subject of debate. We conducted a retrospective study at West China Hospital from 2018 to 2021, enrolling 247 patients with AMI complicated by CS (AMI-CS). Patients were categorized into CA and non-CA groups based on their admission status. Univariate and multivariate Cox regression analyses were performed, with 30-day and 1-year mortality as the primary endpoints. Kaplan-Meier plots were constructed, and concordance (C)-indices of the Global Registry of Acute Coronary Event (GRACE) score, Intra-aortic Balloon Pump in Cardiogenic Shock (IABP-SHOCK) II score, and IABP-SHOCK II score with CA were calculated. Among the enrolled patients, 39 experienced CA and received cardiopulmonary resuscitation at admission. The 30-day and 1-year mortality rates were 40.9% and 47.0%, respectively. Neither univariate nor multivariate Cox regression analyses identified CA as a significant risk factor for 30-day and 1-year mortality. In C-statistics, the GRACE score exhibited a moderate effect (C-indices were 0.69 and 0.67, respectively), while the IABP-SHOCK II score had a better predictive performance (C-indices were 0.79 and 0.76, respectively) for the 30-day and 1-year mortality. Furthermore, CA did not enhance the predictive value of the IABP-SHOCK II score for 30-day (p = 0.864) and 1-year mortality (p = 0.888). Cardiac arrest at admission did not influence the survival of patients with AMI-CS. Active resuscitation should be prioritized for patients with AMI-CS, regardless of the presence of cardiac arrest.

Cardiac arrest and cardiogenic shock complicating ST-segment elevation myocardial infarction in China: A retrospective multicenter study

BackgroundData on the effect of cardiac arrest (CA), cardiogenic shock (CS), and their combination on the prognosis of Chinese patients with ST-segment elevation myocardial infarction (STEMI) are limited. The present study sought to evaluate the clinical outcomes of STEMI complicated by CA and CS, and to identify the risk factors for CA or CS. MethodsThis study included 7468 consecutive patients with STEMI in China. The patients were divided into 4 groups (CA + CS, CA only, CS only, and No CA or CS). The endpoints were 30-day all-cause death and major adverse cardiovascular events. A Cox proportional hazards regression analysis was performed. ResultsCA, CS, and their combination were noted in 332 (4.4 %), 377 (5.0 %), and 117 (1.6 %) among all patients. During the 30-day follow-up, 817 (10.9 %) all-cause deaths and 964 (12.9 %) major adverse cardiovascular events occurred, and the incidence of all-cause mortality (3.6 %, 62.3 %, 74.1 %, 83.3 %) and major adverse cardiovascular events (5.4 %, 67.1 %, 75.0 %, and 87.2 %) significantly increased in the No CA or CS, CS only, CA only, and CA + CS groups, respectively. In the multivariate Cox regression models, compared with the No CA or CS group, the CA + CS, CA, and CS-only groups were associated with an increased risk of all-cause death and major adverse cardiovascular events. Patients with CA + CS had the highest risk of all-cause death (hazard ratio [HR], 25.259 [95 % confidence interval (CI) 19.221–33.195]) and major adverse cardiovascular events (HR 19.098, 95%CI 14.797–24.648). ConclusionsCA, CS, and their combination were observed in approximately 11 % of Chinese patients with STEMI, and were associated with increased risk for 30-day mortality and major adverse cardiovascular events in Chinese patients with STEMI.

Global ischemia induces stemness and dedifferentiation in human adult cardiomyocytes after cardiac arrest

Global ischemia has been shown to induce cardiac regenerative response in animal models. One of the suggested mechanisms behind cardiac regeneration is dedifferentiation of cardiomyocytes. How human adult cardiomyocytes respond to global ischemia is not fully known. In this study, biopsies from the left ventricle (LV) and the atrioventricular junction (AVj), a potential stem cell niche, were collected from multi-organ donors with cardiac arrest (N = 15) or without cardiac arrest (N = 6). Using immunohistochemistry, we investigated the expression of biomarkers associated with stem cells during cardiomyogenesis; MDR1, SSEA4, NKX2.5, and WT1, proliferation markers PCNA and Ki67, and hypoxia responsive factor HIF1α. The myocyte nuclei marker PCM1 and cardiac Troponin T were also included. We found expression of cardiac stem cell markers in a subpopulation of LV cardiomyocytes in the cardiac arrest group. The same cells showed a low expression of Troponin T indicating remodeling of cardiomyocytes. No such expression was found in cardiomyocytes from the control group. Stem cell biomarker expression in AVj was more pronounced in the cardiac arrest group. Furthermore, co-expression of PCNA and Ki67 with PCM1 was only found in the cardiac arrest group in the AVj. Our results indicate that a subpopulation of human cardiomyocytes in the LV undergo partial dedifferentiation upon global ischemia and may be involved in the cardiac regenerative response together with immature cardiomyocytes in the AVj.

Hypothermia in patients with cardiac arrest prior to ECMO-VA: Insight from the HYPO-ECMO trial

AimVenoarterial extracorporeal membrane oxygenation (VA-ECMO) has become a common intervention for patients with cardiogenic shock (CS), often complicated by cardiac arrest (CA). Moderate hypothermia (MH) has shown promise in mitigating ischemia–reperfusion injury following CA. The HYPO-ECMO trial aimed to compare the effect of MH versus normothermia in refractory CS rescued by VA-ECMO. The primary aim of this non-predefined post hoc study was to assess the treatment effect of MH in the subgroup of patients with cardiac arrest (CA) within the HYPO-ECMO trial. Additionally, we will evaluate the prognostic significance of CA in these patients. MethodsThis post hoc analysis utilized data from the randomized HYPO-ECMO trial conducted across 20 French cardiac shock care centers between October 2016 and July 2019. Participants included intubated patients receiving VA-ECMO for CS for less than 6 h, with 334 patients completing the trial. Patients were randomized to early MH (33–34 °C) or normothermia (36–37 °C) for 24 h. ResultsOf the 334 patients, 159 (48%) experienced preceding CA. Mortality in the CA group was 50.9% at 30 days and 59.1% at 180 days, compared to 42.3% and 51.4% in the no-CA group, respectively (adjusted risk difference [RD] at 30 days, 8.1% [−0.8 to 17.1%], p = 0.074 and RD at 180 days 7.0% [−3.0 to 16.9%], p = 0.17). MH was associated with a significant reduction in primary (RD −13.3% [−16.3 to −0.3%], p = 0.031) and secondary outcomes in the CA group only (p < 0.025 for all), with a significant interaction between MH and CA status for 180-day mortality [p = 0.03]. ConclusionsThis post hoc analysis suggests that MH shows potential for reducing mortality and composite endpoints in patients with cardiac arrest and refractory CS treated with VA-ECMO without an increased risk of severe bleeding or infection. Further research is needed to validate these findings and elucidate underlying mechanisms.

SPONTANEOUS CORONARY ARTERY DISSECTION (SCAD) WITH CARDIAC ARREST AT PRESENTATION: A SUBANALYSIS FROM THE DISCO REGISTRY

Abstract Introduction Spontaneous coronary artery dissection (SCAD) is a rare cause of acute myocardial infarction (AMI), which primarily affects young women without traditional cardiovascular risk factors, often presenting as sudden cardiac death. This study aims to investigate the prevalence, characteristics, predictors, and outcomes of cardiac arrest in SCAD patients. Methods The DISCO IT/SPA registry, an international retrospective multicenter study, enrolled 375 SCAD patients from 26 centers in Italy and Spain. Patients were categorized based on the presence or absence of cardiac arrest at admission. Data on demographics, clinical presentation, treatment, angiographic findings, and outcomes were collected. Angiograms were independently reviewed, and outcomes included major adverse cardiovascular events (MACE) and in–hospital bleeding. Results Among 375 SCAD patients, 20 (5.3%) presented with cardiac arrest. Both groups were similar in age, gender distribution, and conventional risk factors, except for a lower prevalence of dyslipidemia in the cardiac arrest group. ST–segment elevation myocardial infarction (STEMI) presentation and angiographic type 2b were independent predictors of cardiac arrest. Revascularization was more frequent in the cardiac arrest group. In–hospital outcomes, except for longer hospitalization, did not differ. On follow–up (average 21 months), MACE rates were similar between groups. Conclusions Cardiac arrest is a notable complication in SCAD, mostly presenting with ventricular fibrillation. The prognosis of SCAD patients presenting with cardiac arrest did not differ from those without, reporting a similar rate of events both in–hospital and during long–term follow–up. STEMI presentation and angiographic type 2b were identified as independent predictors of cardiac arrest in SCAD.

Explainable Artificial Intelligence Warning Model Using an Ensemble Approach for In-Hospital Cardiac Arrest Prediction: Retrospective Cohort Study.

Cardiac arrest (CA) is the leading cause of death in critically ill patients. Clinical research has shown that early identification of CA reduces mortality. Algorithms capable of predicting CA with high sensitivity have been developed using multivariate time series data. However, these algorithms suffer from a high rate of false alarms, and their results are not clinically interpretable. We propose an ensemble approach using multiresolution statistical features and cosine similarity-based features for the timely prediction of CA. Furthermore, this approach provides clinically interpretable results that can be adopted by clinicians. Patients were retrospectively analyzed using data from the Medical Information Mart for Intensive Care-IV database and the eICU Collaborative Research Database. Based on the multivariate vital signs of a 24-hour time window for adults diagnosed with heart failure, we extracted multiresolution statistical and cosine similarity-based features. These features were used to construct and develop gradient boosting decision trees. Therefore, we adopted cost-sensitive learning as a solution. Then, 10-fold cross-validation was performed to check the consistency of the model performance, and the Shapley additive explanation algorithm was used to capture the overall interpretability of the proposed model. Next, external validation using the eICU Collaborative Research Database was performed to check the generalization ability. The proposed method yielded an overall area under the receiver operating characteristic curve (AUROC) of 0.86 and area under the precision-recall curve (AUPRC) of 0.58. In terms of the timely prediction of CA, the proposed model achieved an AUROC above 0.80 for predicting CA events up to 6 hours in advance. The proposed method simultaneously improved precision and sensitivity to increase the AUPRC, which reduced the number of false alarms while maintaining high sensitivity. This result indicates that the predictive performance of the proposed model is superior to the performances of the models reported in previous studies. Next, we demonstrated the effect of feature importance on the clinical interpretability of the proposed method and inferred the effect between the non-CA and CA groups. Finally, external validation was performed using the eICU Collaborative Research Database, and an AUROC of 0.74 and AUPRC of 0.44 were obtained in a general intensive care unit population. The proposed framework can provide clinicians with more accurate CA prediction results and reduce false alarm rates through internal and external validation. In addition, clinically interpretable prediction results can facilitate clinician understanding. Furthermore, the similarity of vital sign changes can provide insights into temporal pattern changes in CA prediction in patients with heart failure-related diagnoses. Therefore, our system is sufficiently feasible for routine clinical use. In addition, regarding the proposed CA prediction system, a clinically mature application has been developed and verified in the future digital health field.

Prophylactic supplement with melatonin prevented the brain injury after cardiac arrest in rats

Prophylactic pharmacotherapy for health care in patients with high risk of cardiac arrest (CA) is an elusive and less explored strategy. Melatonin has possibilities used as a daily nutraceutical to trigger the cellular adaptation. We sought to find the effects of long-term daily prophylactic supplement with melatonin on the victim of CA. Rats were divided into sham, CA, and melatonin + CA (Mel + CA) groups. The rats in the Mel + CA group received daily IP injection of melatonin 100 mg/kg for 14 days. CA was induced by 8 min asphyxia and followed by manual cardiopulmonary resuscitation. The endpoint was 24 h after resuscitation. Survival, neurological outcome, and hippocampal mitochondrial integrity, dynamics and function were assessed. Survival was significantly higher in the Mel + CA group than the CA group (81 vs. 42%, P = 0.04). Compared to the CA group, neurological damage in the CA1 region and the level of cytochrome c, cleaved caspase-3 and caspase-9 in the Mel + CA group were decreased (P < 0.05). Mitochondrial function and integrity were protected in the Mel + CA group compared to the CA group, according to the results of mitochondrial swelling, ΔΨm, ROS production, oxygen consumption rate, and respiratory control rate (P < 0.05). Melatonin increased SIRT3 and downregulated acetylated CypD. The mitochondrial dynamics and autophagy were improved in the Mel + CA group (P < 0.05). Long-term daily prophylactic supplement with melatonin buy the time from brain injury after CA.

Abstract 165: Immediate Internalization of Transplanted Mitochondria in Circulatory Immune Cells After Cardiac Arrest Resuscitation in Rats

Background: Mitochondrial transplantation (MTx) is an innovative technology that has the potential effect for attenuating ischemia reperfusion injury. We previously demonstrated that MTx significantly improves survival and neurological outcomes after cardiac arrest (CA) and resuscitation in rats. However, the underlying mechanism by which MTx enhances CA outcomes remains unclear. Aim: To investigate the hypothesis that injected donor mitochondria are rapidly internalized by circulatory immune cells, particularly monocytes/macrophages, which play crucial roles in post-CA inflammatory signaling. Methods and Results: Adult male Sprague-Dawley rats underwent sham operation or 10 minutes of asphyxial CA followed by resuscitation with CPR. Either a respiration buffer as a vehicle or donor mitochondria labeled with MitoTracker Deep Red (MTDR) was intravenously injected to animals of both groups. In the CA groups, the injection was performed upon achieving spontaneous circulation. Serial blood samples were collected at 30, 75, and 150 seconds after injection. Flow cytometry analysis revealed that a marked increase of MTDR-positive ratios, peaking at 30 seconds, in CD45 + leukocytes, CD3 + T lymphocytes, and CD11b/c + monocytes/macrophages in the MTx-treated CA group compared to the other groups (Figure A). Notably, in sham-operated rats with donor mitochondrial injection, only minimal donor mitochondria were found in the circulating immune cells at those time points. Brain and spleen 1 h post-CA with MTx showed enhanced signals of MTDR measured using an in vivo imaging system, indicating successful transfer of injected mitochondria to organs (Figure B). Conclusion: Our findings demonstrate rapid internalization of injected mitochondria by circulatory immune cells after MTx in post-CA rats, suggesting a pivotal role for circulating immune cells in the mechanism underlying the beneficial effects of MTx in CA resuscitation.

Comparison of flowmeter (transit time flow measurement) values for graft flow in three different surgical methods for isolated coronary artery bypass surgery.

Graft patency is the most important factor in coronary artery bypass surgery. This study aimed to compare the relationship between three different surgical methods and transit time flow measurement (TTFM), which is used to detect technical problems in anastomoses performed during coronary artery bypass graft operations and to correct them if necessary. A total of 110 patients undergoing isolated coronary artery bypass surgery were analysed. Of these patients, 48 were operated on by inducing cardiopulmonary arrest (group 1), 33 were operated on without inducing cardiac arrest (group 2) during cardiopulmonary bypass surgery, and 29 underwent surgery on the off-pump beating heart (group 3). TTFMs were performed on all the patients' grafts. Additional surgical intervention requirements, the need for intra-operative and postoperative inotropic support, and all postoperative follow-up data were compared. In total, 110 patients were measured for 301 grafts. Due to insufficient measurements performed on these patients, additional surgical intervention was performed on five grafts in group 1, five grafts in group 2, and seven grafts in group 3. These interventions enabled a normal flow rate to be achieved. The number of grafts that required revision was highest in group 3. There was no difference between the groups in terms of demographic data, EuroSCORE II, preoperative ejection fraction, postoperative complications and mortality rate. TTFM is important for detecting technical problems in grafts. We believe that all surgical methods can be applied more safely by controlling graft flow.

A ventricular fibrillation cardiac arrest model with extracorporeal cardiopulmonary resuscitation in rats: 8 minutes arrest time leads to increased myocardial damage but does not increase neuronal damage compared to 6 minutes.

Extracorporeal cardiopulmonary resuscitation (ECPR) is an emerging strategy in highly selected patients with refractory cardiac arrest (CA). Animal models can help to identify new therapeutic strategies to improve neurological outcome and cardiac function after global ischemia in CA. Aim of the study was to establish a reproducible ECPR rat model of ventricular fibrillation CA (VFCA) that leads to consistent neuronal damage with acceptable long-term survival rates, which can be used for future research. Male Sprague Dawley rats were resuscitated with ECPR from 6 min (n = 15) and 8 min (n = 16) VFCA. Animals surviving for 14 days after return of spontaneous resuscitation (ROSC) were compared with sham operated animals (n = 10); neurological outcome was assessed daily until day 14. In the hippocampal cornu ammonis 1 region viable neurons were counted. Microglia and astrocyte reaction was assessed by Iba1 and GFAP immunohistochemistry, and collagen fibers in the myocardium were detected in Azan staining. QuPath was applied for quantification. Of the 15 rats included in the 6 min CA group, all achieved ROSC (100%) and 10 (67%) survived to 14 days; in the 8 min CA group, 15 (94%) achieved ROSC and 5 (31%) reached the endpoint. All sham animals (n = 10) survived 2 weeks. The quantity of viable neurons was significantly decreased, while the area displaying Iba1 and GFAP positive pixels was significantly increased in the hippocampus across both groups that experienced CA. Interestingly, there was no difference between the two CA groups regarding these changes. The myocardium in the 8 min CA group exhibited significantly more collagen fibers compared to the sham animals, without differences between 6- and 8-min CA groups. However, this significant increase was not observed in the 6 min CA group. Our findings indicate a uniform occurrence of neuronal damage in the hippocampus across both CA groups. However, there was a decrease in survival following an 8-min CA. Consequently, a 6-min duration of CA resulted in predictable neurological damage without significant cardiac damage and ensured adequate survival rates up to 14 days. This appears to offer a reliable model for investigating neuroprotective therapies.

Effect of Concomitant Cardiac Arrest on Outcomes in Patients With Acute Coronary Syndrome-Related Cardiogenic Shock

Patients with acute coronary syndrome (ACS)-related cardiogenic shock (CS) with or without concomitant CA may have disparate prognoses. We compared clinical characteristics and outcomes of patients with CS secondary to ACS with and without cardiac arrest (CA). Between 2014 and 2020, 1,573 patients with ACS-related CS with or without CA who underwent percutaneous coronary intervention enrolled in a multicenter Australian registry were analyzed. Primary outcome was 30-day major adverse cardiovascular and cerebrovascular events (MACCE) (composite of mortality, myocardial infarction, stent thrombosis, target vessel revascularization and stroke). Long-term mortality was obtained through linkage to the National Death Index. Compared with the no-CA group (n=769, 49%), the CA group (n=804, 51%) was younger (62 vs 69years, p<0.001) and had fewer comorbidities. Patients with CA more frequently had ST-elevation myocardial infarction (92% vs 86%), occluded left anterior descending artery (43% vs 33%), and severe preprocedural renal impairment (49% vs 42%) (all p<0.001). CA increased risk of 30-day MACCE by 45% (odds ratio 1.45, 95% confidence interval 1.05 to 2.00, p=0.024) after adjustment. CA group had higher 30-day MACCE (55% vs 42%, p<0.001) and mortality (52% vs 37%, p<0.001). Three-year survival was lower for CA compared with no-CA patients (43% vs 52%, p<0.001). In Cox regression, CS with CA was associated with a trend toward greater long-term mortality hazard (hazard ratio 1.19, 95% confidence interval 1.00 to 1.41, p=0.055). In conclusion, concomitant CA among patients with ACS-related CS conferred a particularly heightened short-term risk with a diminishing legacy effect over time for mortality. CS survivors continue to exhibit high sustained long-term mortality hazard regardless of CA status.

Calpain inhibitor MDL28170 alleviates cerebral ischemia‑reperfusion injury by suppressing inflammation and autophagy in a rat model of cardiac arrest.

Cerebral ischemia-reperfusion injury (CIRI) is associated with a poor neurological prognosis in patients who have experienced cardiac arrest (CA) and cardiopulmonary resuscitation (CPR). The aim of the current study was to investigate the potential role of a calpain inhibitor in CIRI using a rat model of CA. CA was induced in adult male Sprague-Dawley rats, and MDL28170 (a calpain inhibitor) was administered to the rats within 30 min after the return of spontaneous circulation. Differences between groups were evaluated by measuring survival rate, CPR duration and neurological deficit score. Hematoxylin-eosin staining and Nissl staining were performed to assess cerebral injury, and microstructure and autophagy were assessed by transmission electron microscopy. The levels of calpain-1, calpain-2, calpastatin, interleukin (IL)-1β, tumor necrosis factor (TNF)-α, P62, beclin-1 and LC3 in the brain tissues were determined using western blotting and double immunofluorescence staining. There was no significant difference in CPR duration or survival rate among the groups. At 24 h after CPR, the CA group demonstrated damaged tissue morphology; decreased neurological deficit scores, and P62 expression; and upregulated calpain-2, IL-1βp17, TNF-α, beclin-1 and LC3 levels in the cortex. However, MDL28170 improved neuronal function and suppressed inflammation and autophagy by inhibiting calpain-2 level, but there were no differences in the calpain-1 and calpastatin levels. These results suggest that calpain-2, inflammation and autophagy are involved in CA-induced CIRI. MDL28170 inhibited calpain-2 expression, inflammation and autophagy, which suggests its potential efficacy in treating post-CA nerve damage.

Functional Recovery During Inpatient Rehabilitation in Children With Anoxic or Hypoxic Brain Injury

ObjectivesTo (1) describe characteristics of children with anoxic or hypoxic brain injuries (AnHBI) who presented to an inpatient rehabilitation unit, (2) explore functional outcomes of children with AnHBI at discharge, and (3) examine differences between children with AnHBI associated with cardiac arrest (CA) vs those with respiratory arrest (RA) only. DesignRetrospective cohort study. SettingPediatric inpatient rehabilitation hospital in the Northeast United States. ParticipantsA total of 46 children and adolescents ages 11 months to 18 years admitted to an inpatient rehabilitation brain injury unit (1994-2018) for a first inpatient admission after AnHBI. InterventionsNot applicable. Main Outcome MeasuresPediatric Cerebral Performance Category Scale (PCPC), Pediatric Overall Performance Category, and Functional Independence Measure for Children developmental functional quotients (WeeFIM DFQs) total and subscale scores. ResultsMost children had no disability before injury (PCPC=normal, n=37/46) and displayed significant functional impairments at admission to inpatient rehabilitation (PCPC=normal/mild, n=1/46). WeeFIM and PCPC scores improved significantly during inpatient rehabilitation (WeeFIM DFQ Total, P=.003; PCPC, P<.001), although many children continued to demonstrate significant impairments at discharge (PCPC=normal/mild, n=5/46). Functioning was better for the RA-only group relative to the CA group at admission (WeeFIM DFQ Total, P=.006) and discharge (WeeFIM DFQ Total, P<.001). Ongoing gains in functioning were noted 3 months after discharge compared with discharge (WeeFIM DFQ Cognitive, P=.008). ConclusionsIn this group of children with AnHBI who received inpatient rehabilitation, functional status improves significantly between rehabilitation admission and discharge. By discharge, many children continued to display significant impairments, a minority of children had favorable neurologic outcomes, and children with CA have worse outcomes than those with RA-only. Given the small sample size, future research should examine functional recovery during inpatient rehabilitation in a larger, multisite cohort and include longer-term follow-up to examine recovery patterns over time.

Effect of electroacupuncture at Baihui ameliorated neurologic deficit and hemodynamic stability in rat model of post-cardiac arrest syndrome

To observe the results of electroacupuncture (EA) on the resuscitation of a rat model of asphyxia cardiac arrest (CA). And to explore its effect on the neurologic deficits and hemodynamic instability of post-cardiac arrest syndrome (PCAS). A total of 107 male SD rats were randomly divided into sham, CA, and EA groups. Each group received arterial catheterization and tracheal intubation. The sham group was not induced asphyxia. Asphyxial cardiac arrest was established by endotracheal tube clamping. Rats in the CA group received basic respiratory support and fluid resuscitation in return of spontaneous circulation (ROSC) and rats in the EA group received EA at Baihui based on the treatment of CA group after ROSC, with a dense-dispersed wave at frequencies of 4-20 Hz, while the current intensity was adjusted minimum to induce a twitch of the scalp, the course of treatment was 30 minutes. The baseline data, hemodynamics after ROSC, neurological deficit score (NDS), pathological changes of brain tissue, and levels of serum biomarker were recorded and compared among the three groups. The 72-hour survival of rats was analyzed by Kaplan-Meier survival curve. Hematoxylin-eosin (HE) staining was used to observe the pathological changes of necrotic neurons in the hippocampal CA1 region of rat brain. Meanwhile, Nissl staining and TdT-mediated dUTP nick-end labeling (TUNEL) were used to detect cell apoptosis and injury. Compared with the CA group, the mean arterial pressure (MAP) in the EA group increased significantly at 15 minutes after ROSC [mmHg (1 mmHg ≈ 0.133 kPa): 125.00 (94.00, 136.25) vs. 92.00 (72.00, 122.50), P < 0.05]. There was no significant difference in the NDS score between the EA group and the sham group. Still, the NDS score of the rats in the CA group at 6 hours after ROSC were significantly lower than that in the sham group (46.00±10.61 vs. 80.00±0.00, P < 0.05). Kaplan-Meier survival curve analysis showed that EA did not improve the 72-hour survival rate of rats (100% in the sham group, 25% in the CA group, and 30% in the EA group, P > 0.05). The analysis by TUNEL showed that the apoptosis rate of neurons in CA1 region of the hippocampus in EA group at 6 hours after ROSC was significantly lower than that in CA group [(62.84±2.67)% vs. (71.29±3.70)%, P < 0.05]. Compared with the CA group, the level of serum S100 calcium binding protein B (S100B) in the EA group at 6 hours after ROSC was significantly lower (ng/L: 19.30±13.87 vs. 132.28±31.67, P < 0.05), but there were no significant differences in the levels of tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6) between these two groups. In the present study, EA at Baihui can stabilize the hemodynamic, moreover, it has a particular neuroprotective effect on PCAS rats. Still, EA at Baihui does not reduce the systemic inflammatory response and improve the survival rate of rats, and its mechanism remains to be verified in further research.

The Neuroprotective Effects of Administration of Methylprednisolone in Cardiopulmonary Resuscitation in Experimental Cardiac Arrest Model.

Although advances in diagnosis and treatment of cardiac arrest (CA) could improve neurological outcomes after cardiopulmonary resuscitation (CPR), survival rate and neurological outcome after CA and CPR remain poor. This study aimed to investigate the effect of epinephrine (EP) alone and EP in combination with methylprednisolone (MP) (EP + MP) on some the apoptotic and anti-apoptotic genes and proteins levels expression of the cerebral cortex as well as neuronal death in a CA rat model. Forty-five male Sprague Dawley rats were randomly divided into three groups including the hypoxic CA + EP, hypoxic CA + EP + MP, and sham groups using a simple randomization procedure. In both hypoxic CA groups, CA was induced by asphyxia and immediately after confirmation of CA, the treatment strategies including chest compression or cardiac massage simultaneously with ventilation, and administration of EP alone (20mg/kg, every 3min) and EP (20mg/kg, every 3min) + 30 (mg/kg) of MP were done. The sham group only received anesthetic drugs without CA. Some neurological outcomes were investigated using histopathological, immunohistochemical, molecular, and terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling (TUNEL) assays at 5 and 48h post-CPR. The data obtained showed the highest up-regulation of apoptotic genes and proteins expression, the lowest expression of anti-apoptotic gene and protein expression, the most DNA fragmentation and histopathological changes belonged to the EP group on 48h post-CPR. While mild and intermediate histopathological changes, DNA fragmentation and apoptotic activity was detected in theEP alone and EP + MP groups at 5h and 48h post-CPR, respectively. As a novel finding, the present study showed that EP + MP protects neurons from death provoked/induced by hypoxia and reperfusion injury in an experimental model of CA through up and down-regulation of pro- (caspases 3 and 8) and anti-apoptotic (BCL2) molecules, respectively.

Abstract 107: Systemic Allogeneic Mesenchymal Stem Cell Administration Does Not Attenuate Early Post-resuscitation Brain Injury Or Inflammation In A Porcine Model Of Cardiac Arrest

Introduction: Based on emerging evidence that systemic inflammation exacerbates post-resuscitation organ injury, we recently tested the efficacy of allogeneic mesenchymal stem cell (MSC) administration early after return of spontaneous circulation (ROSC) in a porcine model of cardiac arrest (CA). Initial results indicate that MSCs attenuate post-ROSC cardiac dysfunction, but it is unclear if these protective effects extend to the brain. Accordingly, we aimed to determine if systemic allogeneic MSCs reduce early post-ROSC brain injury and inflammation in swine. Methods: Swine (n=33) were subjected to 10 min CA followed by mechanical CPR with defibrillation and epinephrine (EPI; 0.015 mg/kg iv). Animals that achieved ROSC (n=19) were blindly randomized to intra-arterial saline (n=9) or allogeneic bone marrow-derived MSCs (55±2 x 10 6 ; n=10) 30 min post-ROSC. Blood sampling was performed for 4 hours post-ROSC to quantify serum neurofilament light chain (NFL) levels, after which brain tissue was collected for post-mortem quantification of regional neuronal injury (H&amp;E), activated microglia (IBA-1), and inflammatory gene expression (PCR) vs. healthy control swine (n=8). Results: Animals resuscitated from CA exhibited a significant increase in neuronal injury throughout the brain vs. controls that was not affected by MSC treatment ( A ). Similarly, the post-ROSC rise in serum NFL was not different between saline-treated and MSC-treated animals (2.5±0.6 vs. 2.5±0.8 fold-change vs. baseline; p=0.94). A significant increase in activated microglia ( B ) and inflammatory gene expression ( C ) was observed throughout the brain in both CA groups vs. healthy controls, with particularly prominent changes in the striatum but no notable differences between treatment groups. Conclusions: Despite favorable effects on the heart, systemic allogeneic MSC therapy after ROSC does not significantly affect early markers of brain injury and inflammation in a porcine model of CA.