bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 124: Chest Compression Pause Duration is Associated with Worse Survival Outcomes Following Pediatric In-hospital Cardiac Arrest
Authors: Lauridsen Kasper Glerup , Morgan Ryan W , Berg Robert A , Niles Dana E , Kleinman Monica E , Zhang Xuemei , Griffis Heather M , Kurosawa Hiroshi , Del Castillo Jimena , Skellett Sophie , Lasa Javier J , Raymond Tia T , Duval-arnould Jordan M , Sutton Robert M , Nadkarni Vinay M
Published: November 2020

Introduction:
The association between chest compression (CC) pause duration and pediatric in-hospital cardiac arrest (IHCA) survival outcomes is unknown. We hypothesized that longer maximum CC pause durations are associated with worse survival and neurological outcomes.

Methods:
Cohort study of all index pediatric IHCAs (<18 years of age) ≥1 min in the Pediatric Resuscitation Quality (PediRES-Q) Network from July 2015 through December 2019. We used multivariate logistic regression with mixed effects and robust standard errors to analyze association of 5-sec increments of longest CC pause duration with survival and neurologic outcomes. Favorable neurological outcome was defined as Pediatric Cerebral Performance Category (PCPC) at discharge ≤3 or no change from baseline.

Results:
We identified 371 index IHCAs: median [Q1,Q3] age 2.6 [0.6,9.4] years, female 46%, shockable rhythm 13%, CPR duration 23 [9,47] min. Median length of the longest pause was 17 [8,27] sec. Each 5 sec increase in longest CC pause duration was associated with 6% lower odds for survival with favorable neurological outcome, even after adjusting for age, defibrillation, intubation, extracorporeal CPR, illness category, hypotension as etiology for arrest, CC depth, and clustering by site (aOR 0.94 [95% CI:0.88-0.99], p=0.04). Analyses controlling for the same factors demonstrated an association of longest pause duration with lower odds for survival to hospital discharge (aOR 0.94 [95% CI: 0.90-0.99, p=0.02) and return of spontaneous circulation (aOR 0.91 [(95% CI: 0.86-0.96], p=0.001).

Conclusions:
Longest CC pause duration is associated with favorable neurological outcome, survival to hospital discharge, and return of spontaneous circulation following pediatric IHCA, even when controlling for known confounders and clustering by site. Each 5 sec. increment in longest CC pause duration was associated with 6% lower odds for survival with favorable neurological outcome.
Abstract 126: Intravenous Versus Intraosseous Epinephrine Administration for Pediatric Patients with Out-of-hospital Cardiac Arrest
Authors: Okubo Masashi , Dezfulian Cameron , Guyette Francis X , Martin-Gill Christian , Owusu-Ansah Sylvia , Callaway Clifton W
Published: November 2020

Introduction:
The 2015 American Heart Association Guidelines for Cardiopulmonary Resuscitation recommend intravenous (IV) or intraosseous (IO) epinephrine administration for pediatric patients with out-of-hospital cardiac arrest (OHCA). However, it is unknown whether the route of epinephrine administration affects patient outcomes. Our objective was to evaluate the association between the route of epinephrine administration and survival.

Methods:
We conducted a secondary analysis of the Resuscitation Outcomes Consortium Epistry, a prospective multicenter OHCA registry from 2011 through 2015 in North America. We included pediatric patients (≤18 years) with OHCA for whom emergency medical services (EMS) providers attempted resuscitation and administered epinephrine via IV or IO. We excluded patients who received endotracheal epinephrine, received both IV and IO epinephrine, received IV epinephrine with failed IO access, and received IO epinephrine with failed IV access. The primary outcome was survival to hospital discharge. We used multivariable logistic regression and adjusted for age, sex, initial rhythm, location of arrest, witness status, receiving layperson cardiopulmonary resuscitation, 9-1-1 call to EMS arrival, and advanced airway management. We also conducted a propensity score matching analysis with the same covariates.

Results:
Of the eligible 831 pediatric patients with OHCA, 226 (27.2%) received IV epinephrine and 605 (72.8%) IO epinephrine. Median interval between 9-1-1 call and epinephrine administration was 16.4 minutes (interquartile range [IQR] 12.9-21.0) in IV group and 16.2 minutes (IQR 12.8-20.0) in IO group. In the logistic regression model, the adjusted odds ratio (OR) of the IO group for survival to hospital discharge was 0.99 (95% confidence interval [CI] 0.41-2.40), compared with the IV group. Similarly, in the propensity score analysis, 218 patients underwent matching with good balance (standardized differences <0.25 for all covariates) and the OR of the IO group for survival to hospital discharge was 1.00 (95% CI 0.38-2.62).

Conclusions:
We observed no significant difference in survival to hospital between pediatric patients with OHCA who received epinephrine via IV and IO routes.
Abstract 127: Racial Disparities in Management and Outcomes of Cardiac Arrest Complicating Acute Myocardial Infarction
Authors: Subramaniam Anna , Patlolla Sri Harsha , Vallabhajosyula Saraschandra
Published: November 2020

Introduction:
Racial disparities in outcomes of acute myocardial infarction (AMI) and cardiac arrest (CA) exist. This study assessed the racial differences in the management and outcomes of CA complicating AMI to better inform clinical care.

Hypothesis:
We hypothesized that racial minorities would have worse outcomes with AMI-CA as compared to white patients.

Methods:
During 2012-2017, AMI admissions with a concomitant diagnosis of CA were identified from the National Inpatient Sample. Race was classified as white, black and others (Hispanic, Asian or Pacific Islander, Native American, Others). The primary outcome was racial disparities in in-hospital mortality. Secondary outcomes included racial disparities in invasive procedures and hospitalization characteristics.

Results:
We identified 3,504,225 admissions for AMI in the study period, of which 182,750 (5.2%) were complicated by CA. 74.8% were white, 10.7% were black and 14.5% belonged to other races. Black and other race AMI-CA admissions received less frequent early coronary angiography (41.4% vs 50.2% vs 52.8%), coronary angiography (61.9% vs 70.2% vs. 73.1% %), PCI (44.6% vs 53.0% vs 58.1%), CABG and mechanical circulatory support compared to white and other races. The mean time to coronary angiography was highest among blacks (3.4 ± 4.2 days) and lowest among whites (3.0 ± 3.7 days). Black and other races had significantly higher unadjusted mortality, however in a multivariable logistic regression analysis with white race as referent, black race was associated with lower in-hospital mortality (OR 0.95 [95% CI 0.91-0.99];
p
=0.007) whereas other races had higher in-hospital mortality (OR 1.11 [95% CI 1.08-1.15];
p
<0.001) compared to white race. AMI-CA admissions of black race had longer length of hospital stay, higher rates of palliative care consultation, less frequent DNR status use, and fewer discharges to home. Admissions of other races had higher use of DNR status and higher hospitalization costs compared to whites and blacks.

Conclusions:
Significant racial disparities exist in in-hospital mortality among AMI admissions complicated with CA. Further quantitative and qualitative research into the equitable care of racial minorities with AMI-CA is needed to address this disparity.
Abstract 128: Time for a Change: Use of Doppler Ultrasound for Pulse Checks in Cardiac Arrest Patients
Authors: Cohen Allison , Li Timmy , Becker Lance B , Rolston Daniel , Nelson Mathew , Owens Casey , Gordon Miles
Published: November 2020

Introduction:
During cardiopulmonary resuscitation, the presence or absence of a pulse is critical in guiding the management of cardiac arrest (CA) patients. Despite the importance placed on palpating a pulse, several reports have shown that providers lack accuracy in determining it the presence via manual palpation. The purpose of this study is to assess the sensitivity, specificity, and accuracy of manual femoral pulse detection as compared to Doppler ultrasound pulse detection in CA patients.

Hypothesis:
We hypothesize that a Doppler ultrasound obtained pulse will be more accurate than manual palpation for detecting an arterial pulse in patients in CA.

Methods:
This is a prospective observational study of non-traumatic CA patients that occurred at North Shore University Hospital. During a pulse check, the presence of both a femoral Doppler waveform and manual femoral pulse were recorded simultaneously. These values were compared to the arterial line waveform, which served as the gold standard. During each pulse check, the presence or absence of a pulse was documented, as well as the arterial line measurement. We calculated the sensitivity, specificity, and accuracy of manual palpation and Doppler ultrasound determination of the presence of a pulse.

Results:
We enrolled a total of 23 patients. The sensitivity of Doppler ultrasound detection of a pulse was 0.82 (95% CI: 0.72, 0.93) with a specificity of 1.00 (95% CI: 1.00, 1.00), and accuracy of 0.88 (95% CI: 0.78, 0.94). The sensitivity and specificity of manual palpation of a pulse was 0.27 (95% CI: 0.15, 0.40) and 0.90 (95% CI: 0.78, 1.00), respectively, with an accuracy of 0.46 (95% CI: 0.34, 0.58).

Conclusion:
Determining the presence of a pulse in the management of cardiac arrest patients is a critical step in the Advanced Cardiovascular Life Support algorithm. Our preliminary data suggests that Doppler ultrasound has a higher sensitivity and specificity for detecting a pulse in CA patients and highlights the inaccuracy of manual pulse palpation. These preliminary results could lead to a change in the practice of pulse checks, to favor the use of Doppler ultrasound detection. Further data is needed to determine what blood pressure readings correspond to a perfusable rhythm.
Abstract 130: Mechanical, Team-focused, Video-Reviewed Cardiopulmonary Resuscitation Improves Trends in Survival to Discharge and Cardiac Arrest Performance Measures
Authors: Rolston Daniel , Li Timmy , Owens Casey , Haddad Ghania , Palmieri Timothy , Wolff Jennifer , Blinder Veronika , Cassara Michael , Becker Lance B
Published: November 2020

Background:
Our previous research demonstrated an improvement in ROSC after implementing a bundle including mechanical, team-focused, video-reviewed cardiopulmonary resuscitation (MTV-CPR) for cardiac arrest patients in our ED. The aims of this study are to assess trends in cardiac arrest outcomes and improvements in cardiac arrest performance measures after the implementation of our MTV-CPR intervention.

Methods:
In 2018, our ED began using mechanical CPR; a new team-focused strategy with nurse led ACLS; and biweekly video-review of cardiac arrests. The primary outcome of this study was to evaluate the annual trend in survival to discharge from 2017 (the year before implementing MTV-CPR) through 2019. Secondary outcomes included ROSC and survival to admission. The Cochrane-Armitage test was used to evaluate annual trends in outcomes over the 3-year study period. We also sought to determine if an improvement in cardiac arrest performance measures occurred over the two years of our MTV-CPR intervention using Wilcoxon rank sum and two-sample t-tests. Cardiac arrest performance measures are listed in the table.

Results:
The groups were similar at baseline over the 3-year study period. 291 patients were included in the study (96 in 2017, 96 in 2018, and 99 in 2019). Survival to discharge improved from 3.1% in 2017 to 5.2% in 2018 to 10.1% in 2019 (p= 0.043); ROSC improved from 26% to 41.7% to 40.4% (p=0.038); survival to admission went from 19.8% to 25% to 29.3% but was not significantly different (p=0.124). Results for cardiac arrest performance measures are reported in the table. There were significant reductions in time to bed transfer, rhythm determination, mechanical CPR placement, and duration of each chest compression interruption due to ultrasound.

Conclusions:
Implementation of our MTV-CPR intervention for cardiac arrest patients resulted in improved trends in survival to discharge and ROSC, as well as improvements in multiple cardiac arrest performance measures.
Abstract 132: Cardiopulmonary Resuscitation with Chest Compressions During Sustained Inflations in a Pediatric Porcine Model - A Randomized Control Animal Trial
Authors: Schmölzer Georg , Patel Siddhi , Kim Seung Yeon , Shim Gyuhong , Monacelli Sveva , Lee Tze-Fun , O'Reilly Megan , Cheung Po-Yin
Published: November 2020

Background:
Pediatric resuscitation guidelines recommend continuous chest compressions (CC) with asynchronized ventilation (CCaV) during cardiopulmonary resuscitation (CPR) once an airway has been secured. However, the optimal CC technique remains unknown.

Aim:
To determine if CCs during sustained inflations (SI) improves return of spontaneous circulation (ROSC) of asphyxiated pediatric piglets compared to CCaV.

Intervention and measurements:
Piglets (age 20-23 days) were anesthetized, intubated, instrumented, and asphyxiated. Protocolized resuscitation was initiated when mean arterial blood pressure was <25mmHg with bradycardia. Piglets (n=12/group) were randomized to receive CCaV resuscitation (CCaV group) according to the current resuscitation guidelines, or CC during SI (CC+SI group). The CC+SI group received a SI with a peak inflating pressure of 25 cmH
2
O for 30sec, CCs were provided at a rate of 100/min, and SI was interrupted after 30 sec for one second before a further 30sec SI was provided. CC and SI were continued until ROSC. Respiratory parameters, carotid blood flow, systemic artery pressures, and cerebral oxygenation were measured.

Main results:
Median (IQR) time to ROSC was significantly decreased in the CC+SI group compared to CCaV with 248 (41-346)sec vs. 720 (167-720)sec (p=0.049), respectively. CC+SI had a 100% higher rate of ROSC compared to CCaV with 10(83%) vs. 5(42%) (p=0.089), respectively. Piglets in the CC+SI group received a median (IQR) 3.5 (0-5.8) intravenous epinephrine boluses compared to 8.0 (1.8-11) in the CCaV group (p=0.123).

Conclusions:
Combining CC and SI significantly improved time to ROSC and survival in asphyxiated pediatric piglets when compared to the current standard of CCs with CCaV during pediatric CPR.
Abstract 140: Effects of ω-3 Polyunsaturated Fatty Acids on Systemic Inflammation and Post-resuscitation Myocardial Function in a Rat Model of Cardiac Arrest and Cardiopulmonary Resuscitation
Authors: Cheng Cheng , Li Hui , Jin Tao , Liang Lian , Zhang Guozhen , Bradley Jennifer , Peberdy Mary Ann A , Ornato Joseph P , Wijesinghe Dayanjan , Tang Wanchun
Published: November 2020

Introduction:
Massive systemic inflammation is a primary cause of myocardial dysfunction following cardiac arrest (CA) and resuscitation (CPR). We investigated the effects of ω-3 polyunsaturated fatty acids (ω-3 PUFA) on systemic inflammation and myocardial function after CA and CPR.

Hypothesis:
Administration of ω-3 PUFA at the start of CPR will alleviate post CPR inflammation and improve cardiac function in a rat model of CA and CPR.

Methods:
18 male Sprague-Dawley rats weighing between 450g-550g were randomized into three groups: Sham, Control, and ω-3 PUFA. Ventricular fibrillation (VF) was induced and untreated for 6 min. 4J defibrillation was attempted after 8 min of CPR. Saline placebo or ω-3 PUFA (5mL/kg) was infused at the start of CPR and continued for 4h. Ejection fraction (EF), cardiac output (CO) and myocardial performance index (MPI) were measured by echocardiography at baseline, 1, 3 and 6h after return of spontaneous circulation (ROSC). Inflammatory cytokines (IL-6 and TNF-α) and cardiac biomarker (cTnI) levels in plasma were detected at baseline and 6 hrs after ROSC.

Results:
A decrease in EF and CO and an increase in MPI occurred after resuscitation. Significant improvement was noted in ω-3 PUFA compared to control animals (p<0.05) (Fig. 1). ELISA analysis showed increased plasma IL-6, TNF-α, and cTnI in post-resuscitated rats. Administration of ω-3 PUFA attenuated the rise in these plasma biomarkers (p<0.05) (Fig. 2).

Conclusion:
Administration of ω-3 PUFA attenuates post-resuscitation systemic inflammation and improves myocardial function in a rat model of CA and CPR.
Abstract 141: Early Cytokine Profile in Selectively Vulnerable Brain Regions, Heart and Serum After Asphyxial Cardiac Arrest vs. Ventricular Fibrillation Cardiac Arrest in Rats
Authors: Palmer Abigail A , Uray Thomas , Dezfulian Cameron , Stezoski Jason , Janesko-Feldman Keri , Kochanek Patrick M , Drabek Tomas
Published: November 2020

Background:
Currently, post-resuscitative care for survivors of cardiac arrest (CA) is independent of the etiology of CA. We have previously reported that asphyxial CA (ACA) results in different injury pattern vs. ventricular fibrillation CA (VFCA). Exploration of the early inflammatory response could identify insult-specific targets for future therapies. We hypothesized that the early systemic and regional neuroinflammatory cytokine response could differ between ACA vs. VFCA.

Methods:
Adult male rats were subjected to a 10 min ACA, or 10 min VFCA (n=12/group). Naives (n=12) and shams (n=12) subjected to anesthesia and instrumentation but not CA served as controls. Serum, heart and regional brain cytokine signatures were assessed in selectively vulnerable brain regions: cerebellum, cortex, hippocampus and striatum at 3 h. NSE, S100b and troponin T were also assessed.

Results:
Asphyxiation produced an ~4 min period of severe hypoxemia followed by a no-flow duration of ~ 6±1 min. VF immediately induced no-flow. Brain cytokines in naïve rats were low or undetectable. Shams had a modest effect on selected cytokines. Both ACA and VFCA resulted in robust selected cytokine responses in serum, heart and brain (Fig. 1) with significant regional differences in brain that identified striatum as a selective neuroinflammatory target. No significant differences in cytokines between CA models were observed. NSE, S100b and troponin T were similarly increased after ACA and VFCA vs. naives and/or shams.

Conclusions:
Both models of CA resulted in marked systemic, heart and brain cytokine response. Biomarkers of organ injury were also comparable. Contrasting prior studies showing greater oxidative stress and brain injury in ACA, but greater hemodynamic impairment after VFCA, systemic and brain cytokine profiles revealed similar increases across insults, suggesting that the cytokine response may not mediate key secondary injury differences between these two CA phenotypes.
Abstract 155: Identification of Decreased Plasma Lysophosphatidylcholine Using Phospholipidomics in Cardiac Arrest: A Novel Therapeutic Application
Authors: Nishikimi Mitsuaki , Yagi Tsukasa , Takegawa Ryosuke , Muhammad Shoaib , Hayashida Kei , Yin Tai , Becker Lance B , Kim Junhwan
Published: November 2020

Introduction:
Cardiac arrest (CA) is a significant public health burden with few effective therapies available. Plasma phospholipids are important for proper organ function. We hypothesized that alterations in plasma phospholipids may play an important role in the pathophysiology of CA and normalizing these alterations may be a novel therapeutic application for the treatment of CA.

Objective:
The aim of this study was to test the phospholipid therapy as a novel therapeutic approach in CA.

Methods and Results:
We performed phospholipidomics on plasma samples from CA patients and controls from North Shore University Hospital to identify plasma phospholipids that correlate with injury severity. We then confirmed the finding using our rat model of 10 and 14 min of asphyxia-induced CA. Finally, we tested the effect of administering LPC using the same model. From the phospholipids analyzed, lysophosphatidylcholine (LPC) levels were found to be the most significantly decreased in CA patients, which was also associated with survival of patients. The same trend was observed in the rat model where rats after 14 min CA had significantly lower plasma LPC levels than rats after 10 min CA. We also found that LPC levels began to decrease continuously following resuscitation, but not during the ischemic phase of CA. Finally, we found that LPC administration substantially increased rat survival compared to the control group. Rats who survived in the LPC-treated group displayed significantly improved brain function and the neuroprotective effect of LPC is supported by improved brain histology. We also found LPC treatment increased plasma IL-10 levels and decreased IL-6 levels post-CA.

Conclusion:
Plasma LPC levels inversely correlated with survival and LPC treatment significantly improved brain function and rat survival. This data indicates that the decrease of plasma LPC is a major mechanism responsible for brain damage demonstrating the potential of LPC as a novel therapeutic in CA.
Abstract 207: Molecular Signatures of Sex Differences in Heart Failure with Preserved Ejection Fraction
Authors: Cao Yang
Published: November 2020

Introduction:
Heart failure with preserved ejection fraction (HFpEF) is a complex syndrome involving diastolic dysfunction and metabolic disorders. Women are twice as likely to develop HFpEF as compared to men and present with a greater symptom burden. However, the sex-specific biology of HFpEF is unknown. This study aims to dissect sex-specific molecular signatures of diastolic dysfunction in HFpEF.

Methods:
We developed a ‘two-hit’ HFpEF model with HFD and l-NAME (Nω-nitrol-arginine methyl ester) in C57BL/6J male and female mice. RNA-seq for heart tissue from mice under HFpEF versus Chow condition was performed and results were integrated with multi-omics datasets including hybrid mouse diversity panel (HMDP, a panel of more than 100 inbred strains of mice) and human heart failure cohort to dissect novel gene-by-sex interactions in the heart.

Results:
HFD and l-NAME induced diastolic heart failure phenotypes in both male and female mice. We observed higher E/A (1.68 ± 0.09 vs. 1.40 ± 0.04, p < 0.05 under chow diet), E/E’ (35.82 ± 2.05 vs. 26.13±1.11, p < 0.05 under chow diet; 53.78 ± 3.94 vs. 43.92±2.08, p < 0.05 after HFpEF) and lung weight (wet/dry ratio, 4.51 ± 0.09 vs. 4.15 ± 0.09, p < 0.05 after HFpEF) in females compared to males. Pathway analysis revealed that compared with male mice, female mice exhibited a greater decrease in fatty acid metabolism, insulin signaling, heart development and an enhanced increase in cell cycle, inflammation, cholesterol efflux and serine synthesis upon HFpEF. Together with our high fat/high sucrose diet-induced metabolic disorder HMDP cohort and isoproterenol-induced heart failure HMDP cohort, HFpEF mice revealed that female hearts contained reduced mtDNA copy number relative to males (3102.56 ± 85.70 vs. 3770.43 ± 77.44, p = 4.51E-08). Cardiac mtDNA was inversely correlated with diastolic dysfunction (bicor = -0.307, p = 0.005) and was regulated by gonadal hormones.

Conclusions:
We utilize our systems genetics approach that integrates multi-omics datasets and dissect novel gene-by-sex interactions in the heart. Females exhibit more severe metabolic disorders and mitochondrial dysfunction relative to males, which are responsible for greater diastolic dysfunction of HFpEF.
Abstract 209: Ketone Bodies Ameliorate Cardiac Function in Heart Failure
Authors: Gambardella Jessica , Morelli Marco B. , Wang Xujun , Santulli Gaetano
Published: November 2020

Background:
Beta hydroxibutirrate (BHB) is the main ketone body produced during fasting or carbohydrate deprivation as an alternative fuel. Mounting evidence suggests that after myocardial infarction (MI), the mitochondrial impairment and metabolic failure coincide with increased levels and utilization of BHB. However, whether the BHB increase is adaptive or maladaptive in damaged myocardium, has never been evaluated.

Aim:
Our scope was to explore the effects of BHB on cardiac function after ischemia both
in vivo
and
in vitro
.

Methods and Results:
In cultured cardiomyoblasts, the administration of BHB (3 mMol) reduces the activation of caspase-3 in response to ischemia, as well as the number of tunnel positive nuclei. Specifically, the mitochondrial apoptotic pathway seems affected, as BHB reduces cytochrome-C release induced by ischemia. Mitochondrial structure and interconnections, soundly affected by ischemia, were significantly retained in presence of BHB, as well as mitochondrial membrane potential (assessed via TMRE). The preserved mitochondrial health was further supported by higher levels of PGC1-alpha detected in cells exposed to ischemia plus BHB compared to ischemia alone. To explore the
in vivo
effects of BHB on ischemia damaged- myocardium, we administrated carbohydrate-null diet (
ketogenic diet
, KD) or standard diet-supplemented with BHB, to post-MI mice. Both groups treated with KD and BHB supplemented diet displayed preserved left ventricular ejection fraction respect to untreated infarcted mice. The protective effects of BHB on cardiac phenotype were mirrored by increased levels of PGC1-alpha in the myocardium of treated mice, in terms of protein and transcription levels. Interestingly, in the hearts of mice fed KD and BHB supplemented diet, we observed a marked difference in histone acetylation pattern.

Conclusions:
BHB protects cardiac cells from apoptotic and mitochondrial damage induced by ischemia. Through its ability to regulate epigenetic modifications, BHB could activate a gene expression program able to support mitochondrial function, thereby representing a powerful therapeutic strategy.
Abstract 210: Flavin Containing Monooxygenase 2 Confers Cardiac Protection via Unfolded Protein Response Signaling Modulated by Disulfide Bond Catalysis
Authors: Liu Qingnian , Tao Yue , Ding Hao , Xiao Changchen , Zhou Yu , Ni Cheng , Ke Changle , Wang Jingyi , Wu Rongrong , Fan Lin , Wu Xianpeng , Zhao Jing , Wu Yan , Hu Xin Yang , Wang Jian'an
Published: November 2020

Introduction:
Myocardial infarction (MI) is characterized by cardiac dysfunction and increased cardiomyocyte death, induced mainly by apoptosis. Using an unbiased transcriptome analysis, we identified flavin containing monooxygenase 2 (FMO2) as one of the top-ranked genes involved in the process of MI. In this study, we investigate the roles of FMO2 in ischemic injury and its potential mechanisms.

Hypothesis:
FMO2 exhibits the cardiac protection from MI injury.

Methods:
Male SD rats receiving either adeno-associated virus serotype 9 containing FMO2 shRNA particles (AAV-shFMO2) or FMO2 (AAV-FMO2), and FMO2 knockout rats were subjected to myocardial infarction surgery. Cardiac function, fibrosis, and apoptosis were examined in these rats and related cellular and molecular mechanisms were investigated.

Results:
Cardiac ischemia injury was associated with significant increases of FMO2 levels both in ex vivo and in vivo models. Loss of FMO2 significantly enhanced cardiomyocyte apoptosis and deteriorated cardiac function accompanied by augmented infarct size in infarcted rat hearts, while elevated expression of FMO2 exhibited the opposite results. Mechanically, located on the ER membrane, FMO2 inhibited activation of ER stress-initiated apoptotic proteins including caspase 12 and C/EBP homologous protein (CHOP), via down-regulating upstream unfolded protein response (UPR) pathway. Furthermore, we found that FMO2, as a novel chaperone in ER, directly catalyzed disulfide-bond synthesis to facilitate proteins folding. Finally, structure analysis of FMO2 revealed the active site GVSG for disulfide-bond catalysis, which was confirmed by the molecular docking experiment of GSH with FMO2. However, FMO2 with GVSG mutation failed to catalyze disulfide-bond formation and lost protection from ER stress or apoptosis in cardiomyocytes.

Conclusion:
FMO2 confers cardiac protection from ischemic damage due to improved cardiomyocyte apoptosis through UPR pathway, which is mediated by disulfide-bond catalysis at GVSG active site. Our findings uncover a novel FMO2-involved regulatory mechanism which could serves as a potential therapeutic target for ischemic cardiovascular diseases.
Abstract 212: Effects of Therapeutic Hypothermia on Glymphatic Clearance
Authors: Rajput Padmesh , Lamb Jessica , Lyden Patrick D
Published: November 2020

Objectives:
Therapeutic hypothermia is the most potent protective therapy for cerebral ischemia in pre-clinical models, however clinical trials have failed to show a significant benefit in patient outcomes. We sought to reconcile this discrepancy by investigating whether hypothermia impaired glymphatic system mediated waste clearance from brain parenchyma in a rat model.

Methods:
Sprague -Dawley rats were divided into normothermia and hypothermia groups. Hypothermia was achieved using a perivascular closed-loop cooling circuit implanted one week before the experiments in both the groups. Animals in the normothermia group were kept at 37C while the hypothermia animals were cooled to 33C. Once the targeted temperature was reached, two fluorescent tracers, small molecular weight (Texas Red-Dextran 3KdA) and large molecular weight (FITC -Dextran 2MdA) were injected intracisternally in each animal. Animals in both the groups were monitored for blood pressure and blood gases. Thirty minutes after injection, animals were perfused with 4% paraformaldehyde and 50 micron sections were cut using Leica vibratome. Brain sections were mounted on slides and cover slipped using antifade Fluro gold. Sections were imaged on Carl-Zeiss apotome microscope. For each animal 12 sections were imaged, data was analyzed using NIH Image J software.

Results and Discussion:
Cerebrospinal fluid tracer efflux in brain was significantly reduced in the hypothermia group compared to the normothermia group. This experiment helps provide insight as to a potential reason clinical trials have failed to show benefit in stroke patients, as hypothermia may have an untoward effect of hindering the brain’s natural clearance system from clearing inflammatory molecules and other waste from brain parenchyma.
Abstract 222: Effects of the COVID-19 Pandemic on Care of Out-of-Hospital Cardiac Arrests in Detroit
Authors: Mathew Shobi , Chalek Adam D , Oneil Brian J , Dunne Robert B
Published: November 2020

Introduction:
March 10
th
, 2020 marked the first positive case of SARS-CoV-2 in Detroit. EMS protocol changes were implemented by March 25
th
, 2020 in response to the virus. These modifications restricted intubation and allowed medical control to terminate resuscitation in cases of suspected COVID-19 after 10 minutes of CPR without ROSC. Due to global changes in pre-hospital cardiac arrest care caused by COVID-19, we conducted an analysis to determine OHCA characteristics of patients and fatality rates in the COVID-19 era.

Methods:
CARES data was analyzed between March 10
th
, 2019 - April 30
th
, 2019 and March 10
th
, 2020 - April 30
th,
2020 for comparison before and during the pandemic. Patient demographics, location of arrest, initial rhythms, bystander CPR, EMS interventions and field termination were compared between the two time points. No major factors occurred in 2019 that would potentially skew that data. Descriptive statistics were utilized.

Results:
A total of 475 CARES patients were included during the study period. Total arrests surged in the COVID-19 era from 180 to 295. OHCA for individuals greater than 50 increased from 130 to 243. An initial rhythm of PEA tripled (10 to 30) during COVID-19, possibly due to hypoxia. The percentage of patients with a shockable rhythm declined (7.8 to 5.1). Bystander CPR decreased from 28.9% (52) to 18.3% (54), secondary to an increase of arrests being in non-public places and concern about disease transmission. Nursing home cardiac arrests increased during COVID from 19 to 73, from the previous year. Placement of an endotracheal tube or supraglottic airway by a basic or advanced unit decreased from 68.3% (123) in pre-COVID-19 era to 37.0% (109) in the current state of the pandemic. Termination of resuscitation in the field occurred over 3-fold from the previous year, an absolute increase from 64 to 204.

Conclusion:
There was a 61% increase in cardiac arrests during COVID-19 in Detroit. The pandemic and subsequent protocol changes greatly altered practice. COVID-19 has likely directly and indirectly, due to fear of going to the hospital, affected the number of out-of-hospital cardiac arrests. Additional review is being conducted to further delineate arrest etiologies.
Abstract 227: Cover Up- It's a Code Blue: Protecting Staff without Compromising Patient Outcomes
Authors: Saint Amour Shae , Kiley Brigid , DeMarco Matthew , Sederstrom Jane , Sen Ayan , Singbartl Kai ,   Resuscitation Subcommittee,   Infection Prevention and Control, Patel Bhavesh
Published: November 2020

Introduction:
During the COVID-19 pandemic, hospitals across the globe have been challenged with following the chain of survival with Get With The Guidelines (GWTG) metrics of time to epinephrine, CPR and early defibrillation while ensuring resuscitation teams are protected with recommended PPE. Healthcare organizations are seeking innovative processes to implement PPE during resuscitation events (codes) while maintaining a timely response.

Hypothesis:
Utilization of for PPE for Airborne Precautions for all resuscitation events can be achieved without compromising patient outcomes or GWTG metrics.

Methods:
In collaboration with Infection Prevention and Control (IPAC), the Resuscitation Subcommittee at an academic medical center developed a modified airborne PPE workflow for both inpatient and outpatient resuscitation events. For staff safety, all patients are considered as COVID-19 positive during a code response. Identifying timely donning and doffing techniques of PPE as paramount for maintaining GWTG metrics, a Safety Officer was implemented as an additional member of the code team. The role of the Safety Officer is to assist with the PPE process and to monitor code team compliance. Other measures implemented included attaching PPE supply bags to all code carts for easy access, adding viral filters on the bag valve masks, conducting educational mock code events, and providing online resources for staff. To measure process outcomes, pre COVID-19 pandemic GWTG metrics, mortality, and survival to discharge rates were compared with COVID-19 metrics utilizing the modified airborne PPE workflow.

Conclusions:
Despite additional use of PPE, the hospital has maintained patient outcomes and adhered to the GWTG resuscitation measures of time to epinephrine, CPR and defibrillation while ensuring the utmost safety of the code team during the COVID-19 pandemic.

Table 1:
GWTG-Award Measures *Preliminary Results
Abstract 231: Single Bystander CPR Performance During Drone AED Delivery for Simulated Out of Hospital Cardiac Arrest
Authors: Chow Christine , Blewer Audrey L , Sharpe Edward , Van Vleet Lee , Arnold Evan , Slattery Joseph , Buckland Daniel M , Joiner Anjni , Mark Daniel B , Starks Monique A
Published: November 2020

Background:
Drones have great potential to speed the delivery of AEDs in the critical first few minutes of OHCA. However, it is unclear whether bystanders can balance high-quality cardiopulmonary resuscitation (CPR) with AED deployment. The 2015 AHA CPR guidelines recommend a chest compression (cc) rate of 100-120/minute, cc depth of 50-60mm, and cc fraction of >60%.

Method:
We performed mock cardiac arrest simulations using bystander volunteers, including simulated 911 call, telephone-assisted dispatcher CPR instructions, bystander CPR, drone-delivered AED, and AED application. CPR performance was recorded by a Laerdal Resusci Anne Quality Feedback System and compared between two groups of participants: recent CPR training (<2 years) versus remote (>2 years) or no CPR training. Prior data had shown CPR skill degradation after 2 years. Chi-squared tests compared demographics; T-tests compared age and CPR performance data.

Results:
Between 9/2019-3/2020, 5 simulations were conducted with 51 participants. The mean age was 39.7 years, 56.9% were female, and 78.4% had a college or graduate degree. Racial/ethnic makeup consisted of 64.7% White, 15.7% African-American, 15.7% Asian, and 11.8% Hispanic. 41.2% had recent CPR training (n=21); 58.8% had remote CPR training (n=19) or no CPR training (n=11). There were no differences in demographics by CPR training groups. Participants with recent CPR training had shorter time from CPR initiation to AED shock delivery (3:45 vs. 4:14 [min:sec], p=0.01) and a trend toward higher percent of time with cc depth (77.4% vs 50.4%, p=0.11) and higher cc fraction (46.8% vs 42.9 %, p=0.12). There were no differences for percent of time with cc rate or CPR recoil.

Conclusion:
Overall, CPR quality was low regardless of prior CPR training status. Those recently trained had shorter resuscitation time and appeared to have better CPR performance. Realization of a drone AED networks may require novel CPR programs focused on high-quality CPR.
Abstract 233: Characterizing Impact of State Legislation on Cardiac Arrest Outcomes at K-12 Schools
Authors: Ford Edward , Karabon Patrick , Mann Clay , Goble Monica , Fosse Gwen , Swor Robert A
Published: November 2020

Background:
Cardiac arrests that occur in schools are infrequent, but high-profile events. Many states have enacted school specific legislation regarding automated external defibrillators (AEDs) placement, CPR training and emergency response plans (EAP).

Objective/Aim:
To characterize out-of-hospital cardiac arrests (OHCA) that occur in K-12 schools; and, assess the relationship of U.S. state AED and CPR laws to outcomes of in school cardiac arrests.

Methods:
A retrospective review of in school OHCA was completed with data from the National EMS Information System (NEMSIS) 3.4 database, calendar years 2017-2018. Study subjects were non-traumatic OHCA occurring prior to EMS arrival on K-12 school grounds. Additionally, we conducted a search of Westlaw (Thomson Reuters) to identify current school specific AED, CPR and EAP laws for all 50 states, and created a structured taxonomy for these laws. Datasets were linked by an honest broker and the K-12 school CPR and AED provisions were compared to state legislation.

Results:
During the study period, there were 454 cases of in school cardiac arrest out of the 25.3 million incidents submitted to NEMSIS. We excluded 140, thus leaving 314 arrests for analysis. The average age was 46.7 (SD=24.1), most were over 18 years old (79.4%), and male 221 (70.4%). Bystander CPR (BCPR) was performed in 240 (76.4%) of cases, bystander AEDs were used in 160 (51.0%) cases, and 107 (34.1%) patients received an AED shock. State AED and CPR laws required student CPR training in 78%, school AED placement in 46%, teacher CPR certification in 14%, and school specific cardiac emergency response plans in 32%. We found no increase in BCPR or AED placement in states with school CPR, AED or EAP legislation. These findings persisted regardless of patient age, school type, or legislative mandate (all P
>
0.05).

Conclusion:
Despite the perceived benefit of legislation supporting CPR and AED use in schools, we identified no improved provision of BCPR or AED use in schools in states with such legislation. Given the high proportions of BCPR and AED in states with and without statutes, we believe this data suggests that non-legislative initiatives, which exist in many states, may be an important driver of emergency cardiac care in K-12 schools.
Abstract 250: Effect of Coaching on Dispatch-assisted Cardiopulmonary Resuscitation: A Randomized Simulation Study
Authors: Fukushima Hidetada , Takano Keisuke , Asai Hideki
Published: November 2020

Introduction:
Immediate bystander cardiopulmonary resuscitation (CPR) is essential for the good outcome of sudden cardiac arrest victims. Current guidelines recommend dispatch-assisted CPR (DACPR). Its quality, however, varies from case to case. The aim of this study was todetermine the effectiveness of dispatch coaching on the quality of CPR by lay rescuers.

Methods:
We conducted a DACPR simulation study. Participants with no prior CPR training within 1 year were assigned randomly to one of two DACPR simulations (No Coaching Group: callers were told to perform CPR and the dispatcher sometimes confirmed if the caller was performing CPR or Coaching Group: the dispatcher coached, encouraged, and counted out loud with a metronome). The study participants performed CPR for 2 minutes under the study dispatcher. All performances were recorded by video camera and Resusci Anne® QCPR (Laerdal, Norway).

Results:
Forty-nine participants aged 20s to 50s were recruited, and 48 completed the simulation (Coaching Group, 27, 9 males and No Coaching Group, 21, 16 males). The average rate of chest compressions was 102.5/min in Coaching Group and 109.3/min in No Coaching group (p=0.270). The average compression depth was slightly deeper in Coaching group (43.0mm vs 41.5mm, p=0.695). When compared the average depth of the first 10 compressions to the total average in each group, the depth significantly improved in Coaching group while that decreased in No Coaching Groups (38.4mm to 43.0mm; p=0.020, 42.3mm to 41.5mm; p=0.431, respectively). The chest compression fraction was also high in Coaching Group (99.4% vs 93.0%, p=0.005).

Conclusions:
Participants in Coaching Group performed better CPR compared to No Coaching Group in terms of high flow fraction. Although the average compression depth was below the guideline recommendation in both groups, it significantly improved in Coaching group. This study indicates that dispatch coaching can optimize the performance of bystander CPR.
Abstract 251: Characterizing Bystanders and Their Actions in Response to Out of Hospital Cardiac Arrest
Authors: Torossian Kristopher , Altwail Mina , Paternoster Ryan , Ford Eddie , Swor Robert A
Published: November 2020

Background:
Bystander actions upon witnessing a cardiac arrest are crucial to improving patient survival. Bystander perceptions and actions when witnessing a cardiac arrest are complex and not well understood. Our study has three primary aims: 1) To characterize CA bystanders demographics, 2) To understand the events from patient collapse until EMS arrival, with a focus on telecommunicator or dispatcher-assisted CPR (T-CPR), and 3) Bystander knowledge/ training in CPR and their actions at the time of CA.

Methods:
This is a prospective observational study conducted on bystanders of out of hospital cardiac arrests (OHCA) serviced by EMS agencies in southeast Michigan. OHCA patients were identified from 3/2018- 12/2019, and bystanders of these events surveyed. Surveys were mailed to non-medical addresses with an introductory letter and paper survey. A phone interview was conducted to describe bystander demographics, events from collapse to EMS arrival, and their actions including CPR performance. We inquired regarding telecommunicator CPR instructions (T-CPR), and if CPR was not performed what were the barriers.

Results:
During our study period, 126 surveys were mailed, and of these 47 bystander surveys were completed. The majority of events occurred in private homes (37/47,78.7%). Few patients (10, 21.2%) survived to discharge. The bystander and patient age were (mean, range)were 62.9 (30-91 ) and 69.3 (30-100) respectively. The majority were female 27/47(57.4%), most 43/47 (91.4%) knew the patient and were family (34/47,72.3%). Bystanders knew the patient a median(range) of 32 (0-68) years. A majority of bystanders (31/47,66.0%) had CPR training and 19 performed CPR. Of the 14/47 (27.8%) that received T-CPR instructions, 9 performed CPR. CPR trained bystanders that did not perform CPR(8/31), identified panic, assessment barriers and physical reasons for not performing CPR.

Conclusion:
In this preliminary work, we identify that bystanders to OHCA are most often family, of similar age to the patient and knew the patient for decades. CPR educational programs should prepare trainees to know that they may well respond to loved ones. Further researcher characterizing bystanders and their actions are needed to improve cardiac arrest outcomes.
Abstract 255: National Institutes of Health Research Funding of the Top Science Gaps Recognized in the 2015 American Heart Association Emergency Cardiac Care Guidelines
Authors: Coute Ryan A , Panchal Ashish R , Mader Timothy J , Kurz Michael C
Published: November 2020

Objective:
A descriptive analysis of NIH funding of the top science gaps recognized in the 2015 AHA Emergency Cardiac Care cardiac arrest (CA) guidelines over a five-year period.

Methods:
A search within NIH RePORTER for the period of 2015 to 2019 was performed using the following terms:
“cardiac arrest” or “cardiopulmonary resuscitation” or “heart arrest” or “circulatory arrest” or “pulseless electrical activity” or “ventricular fibrillation” or “resuscitation”.
Grants were identified as CA research (yes/no) using predefined, published criteria. NIH funded CA abstracts were individually reviewed and categorized using the previously recognized ten most urgent science gaps in the 2015 AHA ECC CA guidelines published by Panchal
et al.
The data were analyzed descriptively.

Results:
The search yielded 1,518 NIH-funded grants over the study period, of which 172 (11.3%) were classified as individual CA grants. A total of 42 (24.4%) did not address a top 10 scientific gap. The remaining 130 grants addressed the following scientific gaps: optimization of post-CA care (78 grants, 45.3%), prediction of patients at risk of CA (12, 7%), developing tools for early neuroprognostication (7, 4.1%), hemodynamic monitoring/goal directed resuscitation (4, 2.3%), optimizing educational strategies for providers (4, 2.3%), optimal airway strategies (2, 1.2%), and understanding why bystanders fail to respond (1, 0.6%). Previously existing scientific networks or data centers accounted for 19 (11%) grants and 3 (1.7%) grants addressed both optimizing post-CA care and early neuroprognostication gaps. Recognized scientific gaps in dispatch-directed CPR, individualized resuscitation strategies, and novel technology for out-of-hospital CA identification and response did not receive specifically directed NIH grant funding.

Conclusion:
Additional research funding targeting critical knowledge gaps in the 2015 cardiac arrest guidelines is needed promote broader evidence-based guideline development. Current NIH funding is concentrated in a few areas leaving disparity among recognized high-yield scientific gaps in CA care.