bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 34: Survival and Neurological Outcome of Out-of-Hospital Cardiac Arrest in Los Angeles County: Preliminary Results After Regionalization of Care
Authors: Bosson Nichole , Eckstein Marc , Sung Gene , Koenig William , Kaji Amy , French William , Shavelle David , Thomas Jay , Gorospe Deidre , Rashi Paula , Tadeo Richard , Niemann Jim 
Published: April 2024

Objective: Post-resuscitation care of cardiac arrest patients at specialized centers may improve outcome after out-of-hospital cardiac arrest (OOHCA). The purpose of this study was to describe recent experience with regionalized care of resuscitated patients in a large metropolitan area and compare it to earlier reported outcomes.
Methods: Los Angeles County established regionalized cardiac care in 2006 with a total of 33 designated STEMI receiving centers (SRC) throughout the county. Since 2010, county-wide protocols mandate transport of all OOHCA patients of presumed cardiac etiology with return of spontaneous circulation (ROSC) in the field to a SRC with an established hypothermia protocol. All SRCs treating ROSC patients report the in-hospital mortality and neurologic outcome of these patients to a single registry maintained by the LA County Emergency Medical Services Agency. We report the preliminary results of the first 8 months after this policy change, with the primary outcome variable of neurologically intact survival at hospital discharge, as defined by a Cerebral Performance Category (CPC) score upon hospital discharge of 1 or 2.
Results: There were 663 patients with field ROSC reported by the SRCs. Of these, 110 (17%) died in the emergency department (DOA), and 66 (10%) were awake and responsive upon hospital arrival, leaving 487 patients included in the study analysis. Of these patients, VF was the initial rhythm in 143 (29%), of whom 36 (25%) survived to hospital discharge (SHD) with a CPC score of 1 or 2. 108 (76%) patients with shockable rhythms received therapeutic hypothermia (TH), of whom 32 (30%) had neurologically intact SHD. In the TH group, the OR for CPC 1 or 2 in patients with an initial shockable rhythm was 3.3 (95%CI 1.1-9.5, p = .04), compared with those who did not received TH. In contrast, the SHD rate in Los Angeles in 2001 for a witnessed arrest with a shockable rhythm was 6%.
Conclusion: These results suggest that regionalization of post-resuscitation care improves the rate of neurologically intact survival from OOHCA.
Abstract 342: Developing an In Vivo Model of Ventricular Refibrillation
Authors: Zamiri Nima , Ramadeen Andrew , Hu Xudong , Farid Talha , Masse Stephane , Dorian Paul , Nanthakumar Kumaraswamy 
Published: April 2024

Background
Ventricular refibrillation, defined as re-emergence of VF following successful defibrillation, is as frequent as 79% after out of hospital cardiac arrest, with at least 50% of patients experiencing more than 1 episode of refibrillation. Re-fibrillations are harder to defibrillate and are inversely associated with survival. The mechanism of refibrillation is not known. In order to test hypotheses on preventing or treating refibrillation, a reliable in-vivo refibrillation model is necessary. Pigs have been used as a reliable model to study the efficacy of CPR. Here we present a swine model of ventricular refibrillation following VF.
Methods & Results
Twenty-four Yorkshire pigs were anesthetized. Three Millar catheters were used to measure pressure from abdominal Aorta, RA and LV. An EP catheter was introduced in the RV to induce VF. VF was induced by burst pacing and left untreated for 4 minutes. Then chest compressions were delivered using a pneumatic device at a constant rate of 120/min and manual ventilation was delivered at 6 breaths/min. All animals were defibrillated after 3 min of CPR at 150J, and increasing energy in case of failure. After successful defibrillation, they were observed for a period of 30 min for any occurrence of refibrillation. Refibrillations were treated with defibrillation. The initial VF could not be defibrillated in 3 (12%). Refibrillation occurred in 13 (62%). The mean time to onset of refibrillation was 629 sec after successful defibrillation ranging from 8 to 1600 sec. Mean number of re-fibrillations was 1.14±1.15 (max: 4) with 33.33% (n=7) experiencing more than one episode of refibrillation. Forty-six percent of refibrillations occurred within first 5 min after defibrillation. Overall Survival was 37.5% (n=9). Survival was 38% in re-fibrillation group vs. 44.4% in non-refibrillation group (p=nsS). With regards to initiation, 60% of episodes were preceded by 1 PVC and 20% were preceded by 2 PVCs or more.
Conclusion
We have developed a swine model of ventricular re-fibrillation that resembles reported human data in terms of incidence of re-fibrillation and initiation following VF arrest. This model will serve as a test bed for different pharmacologic and interventional strategies focused on modulating refibrillation.
Abstract 35: A Validation of the Association Between a Quantitative CT Scan Measure of Cerebral Edema and Outcomes Post Cardiac Arrest
Authors: Cristia Cristal , Ho Mai-Lan , Levy Sean , Giberson Tyler , Salciccoli Justin , Cocchi Michael N , Donnino Michael W 
Published: April 2024

Introduction: The presence of cerebral edema post cardiac arrest (CA) may indicate widespread neurologic injury. Previous studies have examined the association between a quantitative measure of brain edema on CT scan and outcome. A calculated gray matter to white matter attenuation ratio (GWR) of <1.2 was associated with near 100% non-survivable injury post CA. These findings have yet to be validated in a separate population.
Objective: To validate whether a GWR <1.2 reliably indicates poor survival post arrest. We also sought to determine the inter-relater reliability among reviewers and develop a novel GWR that may be simpler to use in practice.
Methods: We performed a retrospective analysis of post CA patients admitted to a single center from 2008 to 2012. Inclusion criteria were age >18years, non traumatic arrest, and a brain CTscan within 24 hours of ROSC. Three independent physician reviewers measured attenuation in pre-specified areas.
Results: We evaluated 300 patients, of whom 91 met inclusion criteria and 79 had a technically adequate CT for evaluation. Mean age was 64 years (SD +/- 17); 69% were male. In-hospital mortality was 63%. Approximately 59% of patients received therapeutic hypothermia. For the validation measurement, the interclass correlation coefficient was 0.70. Results of GWR <1.2 are shown in Table. Adjusting the cut-off value to <1.1, no survivors were noted by reviewers 2 and 3 (0/19) and 89% did not survive as judged by reviewer 1 (1/8).
Conclusion: A GWR <1.2 on CT imaging within 24 hours post CA was associated with a high degree of mortality and poor neurologic outcome, however this was not invariably true. Similarly, our experimental model did not perform well enough to be used for prognostication. We caution against implementation based on previous investigations until reasons for these disparate findings are elucidated. A threshold <1.1 may be a safer cut-off to identify patients with low chance of neurological survival.
Abstract 37: External Validation of Termination of Resuscitation Guidelines in the Setting of Intra-arrest Cold Saline, Mechanical CPR and Comprehensive Postresuscitation Care
Authors: Diskin Francis J , Kurz Michael C , Camp-Rogers Teresa R , Peberdy Mary Ann , Ornato Joseph P 
Published: April 2024

Background: The development of Advanced Life Support (ALS) Termination of Resuscitation (TOR) guidelines for Out-of-Hospital Cardiac Arrest (OOH-CA) seeks to improve the efficiency of scarce pre-hospital resources. However, as pre-hospital treatment for OOH-CA evolves and survival improves, these TOR guidelines must be reevaluated in a contemporary context of EMS providing advanced resuscitation care.
Methods: Retrospective review of all adult (>18 years old), non-traumatic, OOH-CA patients (defined as patients with absence of pulse who received either CPR and/or defibrillation) treated by EMS in Richmond, Virginia, from January 1, 2009 to December 31, 2010. In addition to standard ALS, intra-arrest cold saline, mechanical CPR, and transportation to a comprehensive post-resuscitation center (CPRC) was provided. Survival at 30 days was presumed when death could not be verified from publically reportable sources.
Results: Of the 333 OOH-CA patients enrolled, the majority were male (59%), unwitnessed (52%), received no bystander CPR (67%), presented in a non-shockable initial rhythm (79%), with an average age of 62.5 years. Follow up data was obtained 324 (97.3%) of patients with overall survival of 19%, 15%, and 13% at 7, 14, and 30 days respectively. Of the 77 patients TOR guidelines recommended termination, none survived yielding both 100% specificity (95% CI 100- 92.8%) and positive predictive value (95% CI 100-94.1%). However, TOR guidelines recommended transport of 192 of the 269 patient who died, resulting in a sensitivity of 28.6% (95% CI 34.5-23.4%).
Conclusion: The TOR guidelines continue to have a reliable positive predictive value for death even in the setting of advanced EMS resuscitation methods and access to a CPRC. However, as the potential for survival from OOH-CA improves, the efficiency gained from their use is impacted greatly.
Abstract 47: ECG Changes and Poor Outcomes for In-Hospital Cardiopulmonary Arrest in Patients with Multiple Organ Dysfunction
Authors: Hayase Justin , Do Duc , Kim Sunghan , Hu Xiao , Boyle Noel 
Published: April 2024

Background: The likelihood of surviving to discharge after cardiac arrest (CA) is very low for patients with multi-organ dysfunction. However, at time of CA, many patients often undergo resuscitation attempts, which are either unsuccessful or lead to a prolonged, complicated and costly hospital course, ultimately ending in withdrawal of care. In this study, we evaluate the frequency ECG changes occurring prior to CA in patients with multi-organ failure and implications for “code status” discussions.
Methods: We evaluated all “Code Blue” events at UCLA Medical Center, a 520 bed tertiary care hospital, from April 2010 to March 2012, and included all adult CA cases that had significant organ dysfunction in two or more systems with at least 3 hours of continuous telemetry data preceding CA available. We analyzed up to 24 hours of telemetry data prior to CA for any ECG changes from baseline including PR prolongation, QRS widening, ST segment changes, QT prolongation and new onset atrial fibrillation. Charts were reviewed for survival outcomes and code status at time of CA. All cases were adjudicated by a second observer.
Results: There were 30 cases meeting inclusion criteria and included in this study. Of these 15 (50%) were classified as pulseless electrical activity (PEA) arrest, 11 (37%) were bradycardic arrests and 4 (13%) were ventricular tachycardia/ventricular fibrillation arrests. Amongst the PEA group, 13/15 (87%) had any ECG change up to 24 hours prior to CA with QRS widening in 10/15 (67%) and ST segment changes in 6/15 (40%). Amongst the bradycardic group, 8/11 (73%) had any ECG change up to 18.5 hours prior to CA, with QRS widening in 5/11 (45%) and ST segment changes in 4/11 (36%). Survival to discharge was 2/30 (7%) for all patients, with both survivors being discharged to hospice care. At the time of CA, 25/30 (83%) were full code status.
Conclusions: In this limited case series, ECG changes within the 24 hours preceding CA were seen in 77% of patients with multiple organ dysfunction. Survival for this group after CA remains low, with a disproportionately high percentage of patients undergoing extreme life-saving measures despite poor prognosis. These findings may have important implications for discussions regarding the urgency of “code status” with such patients.
Haldane, Hot Dogs and Halitosis: The Anion Nitrite As an Intrinsic Hypoxic Signaling Molecule and New Therapy for Pulmonary Arterial Hypertension
Authors: Gladwin Mark 
Published: April 2024

Nitrate and nitrite have traditionally been considered dietary toxins that increase the risk of stomach cancer. In this lecture we discuss how the scientific discovery was made that nitrate and nitrite are in fact natural signaling pathways in the human body.
Nitrite is now considered a biological reservoir of nitric oxide (NO), present in plasma, red cells and organ systems, that is reduced to NO during physiological and pathological hypoxia. Current studies by multiple research groups indicate that dietary and NOS-dependent nitrite formation may contribute to critical physiological functions such as blood pressure control, hypoxic vasodilation, mitochondrial respiration and the cellular resilience to ischemic stress. Recent studies suggest that a number of cellular enzymes regulate nitrite reduction to NO at different oxygen tensions, with organ system specificity. The role of molybdenum containing enzymes and heme-globin superfamily proteins - hemoglobin, myoglobin, neuroglobin, cytoglobin and the plant and drosophila hemoglobins - are the subject of active current study, and recent advances in this area of investigation will be reviewed. Studies of cytochrome C oxidase, neuroglobin and plant hemoglobins have identified a role for heme coordination in the control of nitrite reduction to NO (six-to-five coordinate regulation of nitrite binding and reduction). New pre-clinical and clinical studies suggest that inhaled and oral nitrite may be able to prevent and reverse established pulmonary arterial hypertension and phase II proof of concept trials are currently in progress in the US and Europe. It is proposed that the nitrate - nitrite - NO pathway represents a fundamentally conserved pathway for energetics and signaling in biology.
Dancing in the Heart of Organellar Proteomes
Authors: Ping Peipei 
Published: April 2024

The rapid development of high accuracy and high sensitivity mass spectrometry technologies has revolutionized our understanding of proteins and their contribution to cellular function. However, there is an increasingly apparent disconnect between these state-of-the-art tools and their effective applications to advance cardiovascular biology and medicine.
Despite progress made in certain areas of investigation, cardiovascular proteomic research faces three major challenges: lack of study designs to accurately pinpoint connections between function and proteomes; limited quantitative information to understand the dynamics of proteomes in disease phenotypes; and the overwhelming quantity and fragmented nature of mass spectra datasets lacking functional annotations. This 2012 Thomas Smith Lecture presentation will provide an overview of the accomplishments in cardiovascular proteomics, highlight the barriers and opportunities in this field, and address the aforementioned obstacles using examples from organellar proteomics investigations, whereby model systems and computational tools are combined to understand human diseases.
Abstract 72: Inhibition of Dynamin Related Protein 1 Mediated Mitochondrial Fission During Cardiac Arrest Is Cardioprotective and Associated with Therapeutic Hypothermia
Authors: Sharp Willard W , Fang Yong Hu , Han Mei , Ryan John , Morrow Erik , Zhang Hannah , Toth Peter , Beiser David , Archer Stephen L 
Published: April 2024

Introduction: Mitochondrial fission increases cellular reactive oxygen species (ROS) and apoptosis but its role in cardiac arrest (CA) is unknown. Dynamin related protein 1 (DRP1) enhances fission by translocating to the mitochondria and is regulated by its phosphorylation at Serine 616 (activating) and Serine 637 (inhibiting). We hypothesized that inhibiting fission and DRP1 during CA would be cardioprotective. We also tested whether therapeutic hypothermia (TH) inhibited fission and DRP1.
Methods: Cardiomyocytes isolated from 1-2 day old C57BL6/J mice were infected with a modified baculovirus containing mitochondrial targeted green fluorescent protein and then exposed to simulated ischemia/reperfusion (IR) at 37C or 30C (TH) to assess mitochondrial morphology. Hearts from Sprague Dawley rats were exposed to 30 min of global IR at 37C ± 5 uM mitochondrial inhibitor of division 1 (Mdivi-1) or 30C (TH) in a Langendorff perfusion system. ROS was measured using MitoSOX tissue staining. Left ventricular end diastolic pressure (LVEDP), left ventricular developed pressure (LVDP), DRP1 gene/protein expression, and mitochondrial morphology (electron microscopy) were assessed. Heart samples were also collected from C57BL/6 mice after an 8-min cardiac arrest induced by KCl.
Results: IR increased cell death, mitochondrial fragmentation, ROS, and LVEDP (62±1 mm Hg vs 9±1 mmHg, n=5, p<0.05) while decreasing LVDP (26±11 vs 77±8 mm Hg, p<0.05) compared to perfusion only controls. In IR, DRP1 Serine 637 decreased two-fold (n=4, p<0.05) while total DRP1 in mitochondrial protein fractions increased two fold (n=4, p<.0001). TH and Mdivi-1 maintained mitochondrial morphology, decreased ROS, inhibited DRP1 Serine 637 dephosphorylation and mitochondrial translocation. TH and Mdivi-1 also maintained LVEDP (12±1 and 14±2 mm Hg, n=5) and LVDP (84±6 and 84±2 mm Hg, n=5) at levels similar to perfusion-only controls.
Conclusions: IR is associated with increased mitochondrial fission, DRP1 activation, ROS generation, and contractile dysfunction in cellular and organ models of IR and in vivo CA. Inhibition of fission and DRP1 with Mdivi-1 and TH are cardioprotective. DRP1 may be a therapeutic target for patients suffering CA or undergoing cardiopulmonary bypass.
Abstract 9027: A Novel Polymorphism Arg146 of the Natriuretic Peptide Receptor-3 Gene Results in a Significant Reduction in Protein Expression Due to Accelerated Degradation
Authors: Pereira Naveen , Dong Lin , Pelleymounter Linda , Moon Irene , Stilling Gail , Eckloff Bruce , Wieben Eric , Yee Vivien , Redfield Margaret , Burnett John , Weinshilboum Richard 
Published: April 2024

Background: The primary role of natriuretic peptide receptor 3 (NPR3) is clearance of natriuretic peptides. Genetic variation in
NPR3
has been associated with blood pressure regulation and obesity. Despite its importance, variation in
NPR3
characterizing coding single nucleotide polymorphisms (SNPs) has not been addressed by resequencing the gene. Objective: We set out to identify and functionally characterize common variation in
NPR3
in 3 ethnic groups. DNA samples from such subjects are studied because common genetic variation needs to be defined initially in “normal” individuals prior to studying drug effect and response. Also, rare variants identified by sequencing are enriched in complex disease traits.

Methods and Results: DNA samples from 96 European-American, 96 African-American, and 96 Han Chinese-American healthy subjects were used to resequence NPR3. There were 105 polymorphisms identified of which 50 were novel, including 8 nonsynonymous (ns) SNPs of which 7 were novel. Expression constructs for the nsSNPs were created and HEK-293 cells were transfected with constructs for wild type (WT) and the variants. Recombinant proteins were analyzed by quantitative Western blot analysis. A significant reduction in NPR3 immunoreactive protein (60% or less of WT) was observed for the following variants Cys3, Arg146, Val499, and Ser477+Asp521. The Arg146 novel polymorphism resulted in the least protein expression (20% of WT). After treatment of WT and Arg146 cells with proteasome (MG132) and autophagy (3MA) inhibtors, it was determined that autophagy and not proteasomes plays an important role in the degradation of the Arg 146 variant protein. Modeling based on the NPR3 x-ray crystallography structure confirmed that the Arg146 variant were not compatible with WT conformation and could result in protein misfolding or instability.
Conclusions: Multiple novel polymorphisms of NPR3 were identified in 3 ethnic groups. There were 4 variant receptors that displayed a significant decrease in NPR3 protein quantity, Arg146 being the variant with the least expression. Degradation of the variant Arg146 was mediated predominantly by autophagy. This SNP could have a significant effect on the metabolism of natriuretic peptides with clinical implications.
Abstract 91: Pharmacologically Induced Hypothermia Minimizing Shivering Following Cardiopulmonary Resuscitation
Authors: Chen Wei , Sun Shijie , Weng Yinlun , Tang Wanchun 
Published: April 2024

Background: Therapeutic hypothermia reduces oxygen consumption and ischemic injury following successful resuscitation; thereby improves outcomes. However, all the currently available physical cooling techniques cause severe shivering which increases systemic oxygen consumption, and makes it more difficult to maintain target temperature. In this study, we examined the effects of pharmacologically induced hypothermia with WIN 55, 212-2 on shivering during hypothermia in a porcine model of CPR.
Hypothesis: We hypothesized that when WIN55, 212-2 is administered following resuscitation together with surface cooling, it will rapidly reduce the body temperature (BT) without shivering; therefore it is easier to maintain the target temperature.
Methods: Ventricular fibrillation was electrically induced and untreated for 7 mins in 21 male swine weighing 35±2kg. Defibrillation was attempted after 5 mins of CPR. The resuscitated animals were randomized to receive the treatment of either WIN 55, 212-2, surface cooling or the combination of WIN55, 212-2 + surface cooling at 5 mins post-resuscitation. The pharmacological cooling was induced by intravenous infused WIN 55, 212-2 (1.0mg/kg/h). The cooling blanket was utilized for surface cooling. The blood temperature, a total dosage of pentobarbital utilization and the incident and duration of shivering during hypothermia were continuously monitored.
Results: During hypothermia, the incident and duration of shivering and the total usage of pentobarbital were significantly reduced in WIN55,212-2 and combination groups when compared with surface cooling group (p<0.001). That was associated with more rapidly decreased blood temperature and easily maintained with 32-34°C in the combination group.
Conclusions: The shivering during hypothermia is minimized by pharmacologically induced hypothermia with WIN 55, 212-2 alone or together with surface cooling. It may provide a new option for inducing hypothermia.
Abstract 9521: Ventricular Dyssynchrony at Baseline Predicts Transplant-Free Long-Term Survival in Patients Treated by Cardiac Resynchronization Therapy
Authors: Prinz Christian , Felice Cinthia D , Lehmann Roman , Schwarz Maria , Prinz Eva-Maria , Bitter Thomas , Vogt Júrgen , Horstkotte Dieter , Lamp Barbara , Faber Lothar 
Published: April 2024

Aim
s: To analyze whether left ventricular dyssynchrony (LVD) at baseline is predictive for long-term outcome in heart failure (CHF) patients with left ventricular (LV) dysfunction and conduction disturbances treated with cardiac resynchronization therapy (CRT).

Methods: In 504 consecutive individuals with CHF scheduled for implantation of a CRT device, LVD was assessed by tissue Doppler imaging (TDI), defined as an electromechanical delay (EMD) difference of ≥40 ms in 2 opposed left ventricular wall regions (septal vs. lateral, anterior vs. inferior). All-cause mortality, heart transplantation, or assist device implantation was defined as combined primary end point. Secondary end points were measures of reverse LV remodeling and of symptomatic improvement.
Results: Mean follow-up was 68±36 months. LVD at baseline was present in 308 patients (61%). Of these, 24% reached the combined primary endpoint in contrast to 58% of patients without LVD (p<0.001). Furthermore, patients with LVD showed pronounced improvement of all secondary end point parameters. An independent association was found between outcome, LVD (β-coefficient in the final model 0.4, p<0.001), and gender (β-coefficient in the final model 0.2, p=0.002).

Conclusions:
LVD at baseline as assessed by TDI is associated with more pronounced reverse LV remodeling and seems to be a predictor for transplant-free long-term survival in CRT recipients.