bluuebunny/crossref_metadata_2025 huggingface dataset:
Abstract 18339: Glutathione S-Transferase P (GSTP) is a Critical Cardioprotective Protein in Heart Failure That Alleviates Apoptosis, Inflammation, and Cardiac Remodeling
Authors: Hamid Tariq , Zhou Guihua , Guo Shang Z , Kingery Justin R , Lewis Robert K , Conklin Daniel , Srivastava Sanjay , Prabhu Sumanth D
Published: April 2024

Heart failure (HF) is characterized by increased lipid peroxidation products (e.g., unsaturated aldehydes) that amplify oxidative injury. Glutathione S-transferases (GSTs) metabolize electrophilic aldehydes by catalyzing their conjugation with glutathione. GSTs are central to antioxidant defense; however, their role in HF is unknown. Accordingly, we hypothesized that GSTP, the most abundant cardiac GST isoform, is a critical antioxidant and anti-inflammatory protein in HF. We examined left ventricular (LV) remodeling following coronary ligation (or sham-operation) in wild-type (WT) and GSTP-/- mice (n = 8-10/group). Echocardiography revealed no baseline cardiac phenotype in GSTP-/- mice. Compared to WT sham 4 wks after surgery, WT HF hearts exhibited significant (p < 0.05): 1) LV dilatation (EDV 76 ± 33 vs 53 ± 2 μL) and systolic dysfunction (LVEF 51 ± 5 vs 67 ± 3 %); 2) hypertrophy (LV/tibia length [TL] 5.3 ± 1.0 vs 4.1 ± 0.3 mg/mm); 3) ∼30-40% downregulation of myocardial GSTP and GSTPA protein; 4) ∼4-fold increase in protein-acrolein adducts; 5) ∼3-fold increase in myocardial apoptosis by TUNEL staining; and 6) inflammatory activation as indexed by NF-κB DNA binding activity and mRNA levels of interleukin (IL)-1β and IL-6. In contrast, as compared to WT HF, GSTP-/- HF hearts had significant (p < 0.05): 1) worsening of LV dilatation (LVEDV 112 ± 51 μL), systolic dysfunction (LVEF 37 ± 5 %), and wall thinning (anterior wall thickness [AWT] 0.47 ± 0.15 vs 0.57 ± 0.11 mm), but similar degrees of LV chamber hypertrophy; 2) augmentation of protein-acrolein adducts; 3) NF-κB activation, and 4) 2-5-fold increase in IL-1β and IL-6 expression. Importantly, GSTP-/- HF hearts also exhibited a ∼2-fold increase in apoptosis over WT HF, suggesting that differences in cell loss accounted for comparable degrees of chamber hypertrophy despite differences in LV dilatation. We conclude that there is decreased capacity for metabolizing toxic aldehydes in the failing heart with downregulation of GSTP and GSTA. GSTP plays a key cardioprotective role in HF, and alleviates pathological LV remodeling, inflammation, and apoptosis in the failing heart. GSTP-mediated cardioprotection may be in part related to its detoxification of reactive lipid peroxidation-derived aldehydes.
Abstract 18372: Clinical Threshold of Adenovirus Genome Load in Myocardial Tissues of Patients with Myocarditis and Dilated Cardiomyopathy
Authors: Sharma Mirnalini , Mishra Baijayantimala , Kumari Vandana , Saikia Uma N , Bahl Ajay , Ratho Radha K , Talwar Kewal K
Published: April 2024

Background:
Viral myocarditis is rarely recognized hence it is one of the most challenging diagnosis in cardiology. It leads to chronic dilated cardiomyopathy (DCM) and heart failure. Adenovirus is one of the most common cardiotropic viruses that cause viral myocarditis. However, the knowledge on AdV load in adenovirus associated myocarditis or DCM is unknown so far.

Aim:
To gain insight into the pathogenesis of AdV associated myocarditis, present study was aimed to determine AdV load in myocardial autopsy tissue of patients with myocarditis or DCM.

Methods and Results:
AdV load was determined using Taqman Real Time PCR in myocardial autopsy tissues obtained from 24 (11 male and 13 female) patients with histologically proven myocarditis or DCM whereas 12 noninflamed normal hearts obtained from autopsies served as controls. The AdV associated myocarditis was characterized by high mean viral load of 2034 genome equivalents (ge) per microgram of isolated nucleic acids in DCM patients with myocarditis as compared to viral load of 362 genome equivalents (ge) per microgram in normal hearts (p<0.005). Thus, from this data possibly AdV loads of more than 450 ge per microgram in myocardial autopsy are clinically relevant threshold for the maintenance of myocardial inflammation.

Conclusion:
The present study could derive the significant level of adenovirus load of 450 ge per microgram in myocardial tissues to be associated with adenovirus myocarditis and DCM. The knowledge on the clinical threshold of adenovirus load would help in diagnosing the clinically suspected viral myocarditis or DCM cases as well as would help in establishing an antiviral strategy to treat these patients.
Abstract 18375: A Luminal Calcium Sensing Deficient Mutation of the Cardiac Ryanodine Receptor Diminishes Stress-Induced Ventricular Tachycardias in Calsequestrin Null Mice
Authors: Zhang Jingqun , Guo Ang , Koop Andrea , Zhou Qiang , Song Long-Sheng , Chen S.R. Wayne
Published: April 2024

Catecholaminergic polymorphic ventricular tachycardia (CPVT) is an inherited arrhythmogenic disease associated with syncope and sudden cardiac death. Naturally occurring mutations in the cardiac ryanodine receptor (RyR2) and calsequestrin (CASQ2) have been linked to CPVT. The sarcoplasmic reticulum (SR) calcium content and the sensitivity of RyR2 to activation by luminal calcium are some of the key factors determining the propensity for Store Overload Induced Calcium Release (SOICR) and SOICR-evoked VTs. We have recently found that the residue E4782 located in the helix bundle crossing (the ion gate) of the RyR2 calcium release channel acts as a SR store calcium sensor responsible for luminal calcium regulation of RyR2 and SOICR. Interestingly, we found that E4782Q mutation completely protected against SOCR-evoked VTs in a CPVT mouse model harboring the disease-causing RyR2 mutation R4496C. In this present study, we determined whether the E4782Q mutation is capable of rescuing the VT phenotype of the CASQ2 null mice, another mouse model of CPVT. We bred E4872Q+/- mice with the CASQ2 null mice to produce CASQ2-/- or CASQ2+/- with or without the heterozygous E4872Q mutation. After the injection of epinephrine (1.6mg/kg) and caffeine (120mg/kg), CASQ2-/- / E4872Q-/- and CASQ2+/- / E4872Q -/- mice showed long lasting VTs during 30-min of ECG recording (83% and 33%, respectively). On the other hand, CASQ2-/- / E4872Q+/- and CASQ2+/- / E4872Q -/- displayed little or no VTs (6.5% and 0.8%, respectively, p < 0.001, when compared with CASQ2-/- / E4872Q -/-, and CASQ2+/- /E4872Q -/-, n=7~9, for each group). Thus, the E4872Q mutation nearly completely rescued the CPVT phenotype in CASQ2 null mice. These observations indicate that targeting the luminal calcium sensor of the RyR2 calcium release channel represents a new and promising therapeutic strategy for treating CPVT and other calcium mediated cardiac arrhythmias.
Abstract 2: Intra-arrest Induction of Therapeutic Hypothermia via Large-Volume Ice-Cold Saline Infusion Improves Immediate Outcomes for Out-of-Hospital Cardiac Arrest
Authors:   NYC Project Hypothermia Working Group, Freese John
Published: April 2024

Background:
New York City Project Hypothermia is a collaborative effort involving the Fire Department of New York (FDNY), Greater New York Hospital Association, Health and Hospitals Corporation, the Regional Emergency Medical Advisory Committee, and the New York State Department of Health. As part of this effort, the FDNY implemented a pilot protocol in the New York City 9-1-1 System on August 1, 2010 that introduced the induction of therapeutic hypothermia during initial resuscitation efforts via large-volume ice-cold saline infusion.

Purpose:
We sought to assess the effects of this protocol on immediate survival end-points following out-of-hospital cardiac arrest (OOHCA).

Methods:
OOHCA data was analyzed for the following periods: August 1, 2009 - May 31, 2010 (historicalcontrol group) and August 1, 2010 - May 31, 2011 (study group). Except for the intra-arrest induction of hypothermia, no other aspect of the regional resuscitation protocols differed between the two periods. Standard Utstein definitions were utilized. Due to the large sample sizes, Chi-square analyses without Yates' correction were utilized, and a p <0.05 was considered significant.

Results:
5,582 resuscitations for nontraumatic adult cardiac arrests during the control period were compared to 4,727 resuscitations in the study period that included the intra-arrest induction of hypothermia. The groups did not differ with respect to age, response time, bystander witnessed status, or frequency of bystander CPR. Patients in the study period were less likely to be male (52.3% vs 54.6%, p = 0.019), less likely to be white (32.8% vs 35.1%, p = 0.013), and less likely to have an EMS-witnessed arrest (8.3% vs 9.5%, p=0.026). Return of spontaneous circulation (ROSC) and sustained ROSC were improved in the study group as compared to the control group: 31.7% vs 29.0% (p=0.003) and 24.1% vs 21.9% (p=0.0014), respectively.

Conclusion:
The initiation of therapeutic hypothermia via large volume, ice-cold saline infusion results in improved immediate survival for non-traumatic out-of-hospital cardiac arrest. To our knowledge, this is the first report to describe the use of intra-arrest hypothermia in humans and to demonstrate such an effect.
Abstract 211: Cardiopulmonary Resuscitation/Automated External Defibrillator Olympic Competition Enhances Resuscitation Skills in High School Students
Authors: Haley Danielle M , Dugan Noreen P , Hall Christopher N , Guo Rong , Nadkarni Vinay , Vetter Victoria L
Published: April 2024

Introduction:
Bystander cardiopulmonary resuscitation (CPR) rates are 15-30%. We aimed to help students develop innovative CPR/AED (automated external defibrillator) training programs in Philadelphia high schools and to assess their efficacy.

Hypothesis:
Harnessing adolescent characteristics of teamwork, competitiveness, and creativity will produce novel and effective methods of learning resuscitation skills.

Methods:
Health education classes in 15 Philadelphia School District high schools were selected, with 1 control and 1 study intervention group per school. Both groups completed CPR/AED pre- and post-tests to assess cognitive knowledge and psychomotor skills. After pre-tests, both groups were taught CPR skills and AED use by their health teacher. Study groups developed innovative programs to learn, teach, and retain CPR/AED skills. The study culminated with the CPR/AED Olympic event in a sports stadium with study group students from 12 schools competing in multiple CPR/AED skills events including a Mock Code and CPR/AED program presentations. Outcomes included post-tests, Mock Code (17 performance factors), and presentation scores with analysis using paired student's t tests.

Results:
Students' cognitive and psychomotor skills improved with standard classroom education programs (p<0.0001). Competition with other schools at the CPR/AED Olympics and the development of their own student-directed education programs resulted in further remarkable improvements. Participants averaged 93.1% on the Mock Code with 10 of 12 schools ≥94%.

Conclusion:
Students who developed creative and novel methods of teaching and learning resuscitation skills showed outstanding application of these skills in a Mock Code. Harnessing adolescent characteristics of teamwork, competitiveness, and creativity produced novel and effective methods of teaching resuscitation skills, potentially empowering a new generation of effectively trained CPR bystanders.
Abstract 250: Prehospital Teleconsultation in Acute Coronary Syndromes: Feasibility and Effects
Authors: Fischermann Harold , Skorning Max , Bergrath Sebastian , Krüger Stefan , Schröder Jörg , Fitzner Christina , Rörtgen Daniel , Beckers Stefan K , Rossaint Rolf
Published: April 2024

BACKGROUND:
Transmission of 12-lead ECG (ECG) to a specialist in acute coronary syndromes (ACS) is beneficial but not routinely integrated into Emergency Medical Services (EMS). Prehospital teleconsultation (TC) with comprehensive data transmission is a new approach. The feasibility and effects on emergency care of ACS were investigated.

METHOD:
TC was performed between one ambulance and a TC center including real time transmission of voice, ECG, vital data, pictures and video. Standard EMS with ECG transmission via fax served as control. Patients with suspected ACS from May 3 to September 30, 2010 on workdays were included. Primary outcomes: guideline coherent treatment (ECG performance, indicated oxygen and drug administration), time intervals, choice of appropriate facility, quality of prehospital diagnosis and hospital length of stay (LOS). Secondary outcomes: Information content of patient care reporting (PCR), system utilization and technical observations.

RESULTS:
Overall 939 patients were treated - 289 by the TC ambulance and 650 by standard EMS. Thereof 41 patients in the study group and 67 in the control group met the inclusion criteria. TC vs. control: Baseline data and guideline coherent treatment did not differ. On-scene time was prolonged in non-ST-elevation ACS (26 vs. 19 min, p<0.0001) but not in ST-elevation myocardial infarction (22.5 vs. 20 min, p=0.45). Remaining time intervals, the quality of prehospital diagnosis and LOS showed no difference. Urgent percutaneous coronary intervention (PCI) was performed in 16 (76%) vs. 15 (45%) patients (p=0.047). One (9%) vs. 5 (25%) patients were transferred secondarily from a community hospital for PCI (p=0.38). Information content of PCR improved with TC (p<0.0001). Utilization vs. dysfunction for single applications (%): voice 100 vs. 29; ECG 95 vs. 23; realtime vital data 100 vs. 24; pictures 61 vs. 12; video 35 vs. 14.

CONCLUSION:
The system is safe, feasible and without impairing effect on relevant time intervals. Treatment with TC was at least equivalent to a high level standard EMS with ECG transmission and led to improved mission documentation. TC holds the potential to optimize patient care, safety and information flow to the hospital. Trials Registration:
ISRCTN83270177
Abstract 251: iRescU---Saving Lives and Data: A New Multiplatform App to Integrate Social Media and Bridge Logistic Challenges in the Chain of Survival
Authors: Levick Nadine ,   iRescU Rsch Team
Published: April 2024

Introduction:
Of 300,000 USA out-of-hospital cardiac arrests <10% survive, and an AED used in <2%, yet in ~4/5 there is a shockable rhythm. Studies demonstrate bystanders are often uncomfortable to perform CPR, locate or use an AED, and often ineffective in cardiac emergencies.

Objective:
To develop a freely available CPR/AED smartphone app designed for lay use with gratis community dissemination.

Methodology:
A multidisciplinary team designed app, optimizing features available in smartphones, utilizing cutting edge cloud based and crowd source technologies to be an easy access tool for the lay person for training, and when faced with life threatening cardiac emergency, as well as providing enhanced AED location access and two way valuable datasets to Emergency Services and public health researchers.

Results:
The iRescU CPR App is <1mb, designed for deployment to multiple mobile platforms, functioning as both a data terminal and a data resource, with modes addressing; CPR/AED/EMS support in an emergency setting, CPR/AED training mode and AED geolocation. The design is simple high contrast screens, clear text information (international language capability), adherence to AHA and/or ERC guidelines with no medical jargon, use of visual, auditory, and haptic feedback to enhance CPR performance, and uses standard GPRS/GPS technology to access a live expanding AED database to provide relevant real time AED location information, with scope to interact with emergency services and resources. iRescU can operate without connectivity, and is capable of saving data, and uploading when connectivity is restored. Initial evaluation completed, operational field evaluation is underway with five pilot sites for initial AED geolocation capture. A creative dissemination plan involves both health care and non-healthcare strategies

Conclusions:
The effectiveness of the lay public's key role in initiating effective CPR, locating and using an AED is a major challenge to achieving improved cardiac arrest outcomes. Current methods for reliably locating the nearest AED are limited. This App bridges existing logistics gaps in the chain of survival providing a freely available tool for the lay public to enhance their effectiveness in improving cardiac arrest outcomes.
Abstract 257: The Induction of Mild Hypothermia Improves Myocardial β-Adrenergic Responsiveness During Endotoxemia in Pigs
Authors: Wallner Markus , Schwarzl Michael , Seiler Sebastian , Huber Stefan , Steendijk Paul , Mächler Heinrich , Truschnig-Wilders Martini , Pieske Burkert , von Lewinski Dirk , Post Heiner
Published: April 2024

Background:
Mild hypothermia (MH) exerts anti-inflammatory effects in experimental settings. We tested the effect of MH on myocardial ß-adrenergic responsiveness during experimental endotoxemia.

Methods:
Anesthetized pigs (65±2 kg) were acutely instrumented (closed chest) with a series of catheters including a Swan-Ganz catheter, a left ventricular (LV) pressure-volume catheter, an intraaortic balloon catheter and an intravascular cooling device. Endotoxemia, a model of septic shock, was induced by lipopolysaccharid (LPS) infusion at 0.5 µg/kg/h for 1 hour and 1 µg/kg/h for further 3 hours. With the beginning of LPS infusion, pigs were assigned to either normothermia (NT, 38 °C, n=7) or MH (33 °C, n=6). Animals were followed for a total of 8 hours. After sacrifice, ventricular muscle strips were isolated, stretched to optimal length in Tyrode solution containing 2,5 mmol calcium, stimulated at 1 Hz and exposed to increasing concentrations of isoproterenol. All muscle strips were examined at 38 °C.

Results:
In vivo, LV pressure-time (dP/dt) and pressure-volume analysis indicated a similar impairment of LV contractile parameters. In vitro, the increase of developed force in response to isoproterenol was higher in muscle strips isolated from hearts of the MH group than of the NT group. The logEC50% was not different between groups.

Conclusion:
These data indicate that MH counteracts the loss of myocardial ß-adrenergic responsiveness typically associated with the development of sepsis. MH may be a therapeutic option for septic cardiomyopathy.
Abstract 264: Therapeutic Hypothermia Cardioprotection Is Associated with Enhanced pAMPK but Not ATP Preservation
Authors: Sharp Willard W , Shao Zuo-Hui , Han Mei , Li Chang-Qing , Hamann Kimm , Beiser David , Vanden Hoek Terry
Published: April 2024

Introduction:
Therapeutic Hypothermia (TH) is cardioprotective following ischemia/reperfusion (I/R) injury and improves survival following cardiac arrest in an Akt dependent manner. AMP activated protein kinase (AMPK) is a highly conserved, cardioprotective, sensor of cellular energetic stress and ATP depletion that is activated by ischemia. Phosphorylated AMPK (pAMPK) is also a significant inhibitor of the mammalian target of rapamycin complex 1 (mTORC1) that is activated by Akt but inhibited by TH. In this study we hypothesized that TH enhances pAMPK independent of cellular ATP while increasing cell survival. We further hypothesized that strategies to enhance pAMPK would mimic TH cardioprotection by inhibiting mTORC1.

Methods:
Cardiomyocytes isolated from 1-2-day old C57BL6/J mice, were exposed to simulated Ischemia (90 min) followed by reperfusion. For TH, cells were cooled from 37C to 32C during ischemia and the first hour of reperfusion. Protein lysates were collected at serial time points for changes in pAMPK by western blot analyses. ATP measurements were made using a standard bioluminescence assay.

Results:
pAMPK was significantly increased during ischemia as compared to controls. During reperfusion, pAMPK decreased but was maintained by TH (n=5, p<.05). Total AMPK was unchanged. Total cellular ATP decreased significantly with ischemia and TH to 6% and 13% of controls (n=5, p<.05). Following 30 minutes of reperfusion, ATP increased to 9% (IR) and 26% (TH) of controls. Although total cellular ATP increased with TH, these changes were not significant and remained substantially reduced from controls. Cardiomyocyte cell death during ischemia was minimal but increased during reperfusion (4% vs. 46%, p.05, n=5). This cell death was attenuated by TH (24%, p<.05, n=5). The pAMPK activator metformin (100um) similarly attenuated reperfusion associated cell death (22%, p<.05, n=4) while inhibiting mTORC1.

Conclusions:
TH is associated with enhanced cardiomyocyte survival and pAMPK following IR. These events were not associated with enhanced ATP preservation during ischemia. Pharmacologic strategies to mimic TH effects on AMPK may be beneficial to enhance survival following cardiac arrest.
Abstract 277: Midterm Outcome of Aortic Valvuloplasty Utilizing an Autologous Pericardial Patch in Patients with Severe Aortic Regurgitation
Authors: Otsuka Takenori , Suzuki Makoto , Yoshikawa Hisao , Hashimoto Go , Ishikawa Youko , Ishida Takako , Osaki Tsukasa , Matsuyama Masayoshi , Yamashita Hiromasa , Uchida Shin , Moroi Masao , Nakamura Masato , Ozaki Shigeyuki , Sugi Kaoru
Published: April 2024

Background:
We previously reported our experience with an aortic valve plasty (AVP) technique for repairing a stenotic aortic valve. We investigated the feasibility of AVP in patients with aortic regurgitation (AR).

Method:
Ninety patients underwent aortic valve plasty using a pericardial patch. Patients characteristics of the patients were as follows: mean age; 68 ± 12 years; the left ventricular ejection fraction, 56 ± 12%; and the left ventricular end-diastolic dimension, 58.1 ± 5.8 mm. Transesophageal and transthoracic echocardiography were performed up to three year after the operation.

Results:
There was no postoperative AR in 81 patients and trivial postoperative AR in 9 patients. The peak systolic pressure gradient across the aortic valve was 14.5 ± 5.6 mm Hg after valve plasty. No patient underwent reoperation for any reason. Peak systolic gradient was significantly lower in aortic valve plasty group compared with aortic valve replacement group using biosprosthetic valve with or without stent (14.5±5.6 vs 28.6±10.2, respectively, p< 0.001).The peak systolic gradient was 13.0 ± 7.1 mm Hg after two year. Up to three years later, there was no significant increase in the peak systolic gradient or significant worseningin AR (Figure).

Conclusion:
Aortic valve plasty using an autologous pericardial patch to treat aortic regurgitation is safe and feasible
Abstract 38: Nationwide Epidemiology and Outcomes from Pediatric Out-of-Hospital Cardiac Arrest in Japan: From the JCS-ReSS Research Group
Authors: Shimizu Naoki , Ohta Kunio , Nitta Masahiko , Yonemoto Naohiro , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi ,   JCS-ReSS Rsch Group
Published: April 2024

Background:
Though Resuscitation Outcomes Consortium (ROC) reported large volume epidemiology from US and Canada in 2009, data for paediatric cardiac arrest is still scant. Nationwide, prospective, population-based, observational larger study has done in Japan. We reported epidemiology and outcomes from paediatric out-of-hospital cardiac arrest (OHCA) in Japan with comparison to ROC study.

Methods:
Nationwide OHCA registration performed from 2005 to 2009, and gathered 547,218 cases. We enrolled 11,322 children aged less than 20 years, and were stratified into 3 age groups as same as ROC study [infants (<1 y, n 4,006), children (1-11 y, n 3,372), adolescents (12-19 y, n 3,944)]. Initial cardiac rhythms (VF/VT versus Asys/PEA), pre-hospital intervention done by emergency medical teams (EMT), and outcomes were analyzed.

Results:
The incidence of paediatric OHCA in Japan was 9.81 per 100,000 person-years (74.32 in infants 5.46 in children, 8.17 in adolescents), versus 8.04 in ROC. Good neurological outcome (CPC 1 or 2) for all paediatric OHCA was 5.4% (2.9% for infants, 7.5% for children, 6.2% adolescents) versus 6.4% survival to hospital discharge in ROC. In VF/VT group showed similar trends to ROC, but in Asys/PEA group, good neurological outcome was only 1.1% versus 5% in ROC (p <0.005). Analysis of EMT intervention showed defibrillation performed in 95% for adolescents, but only 59% for children and 48% in infants despite indicated. Implementation ratio of other procedure for children was 20% for advanced airway (73% in ROC), 1.7% for resuscitation drug therapy (30% in ROC), 7.1% for IV line (42% in ROC), none for IO line (38% in ROC) in Japan.

Conclusion:
This study demonstrates that the incidence of paediatric OHCA and outcome of VF/VT group are similar to previously reported epidemiology from North America. Asys/PEA group showed significantly worse outcome in Japan. It may relates to the low implementation ratio of pre-hospital intervention by EMT for children in Japan.
Abstract 4: Resuscitation with Adenocaine and Magnesium Reduces Fluid Requirement and Improves Cardiac Function Following 72% Blood Loss in the Pig
Authors: Granfeldt Asger , Nielsen Torben Kær , Sølling Christoffer , Dobson Geoffrey P. , Wogensen Lise , Vinten-Johansen Jakob , Tønnesen Else
Published: April 2024

Introduction:
Fluid therapy following severe hemorrhagic shock triggers ischemia-reperfusion (I/R) injury and multi-organ dysfunction. The combination of adenocaine (adenosine and lidocaine), and Mg2+ (ALM) has been shown to stabilize cardiac function and hemodynamics after myocardial I/R.

Hypothesis:
ALM in 7.5%NaCl at resuscitation: 1) reduces fluid requirements during permissive hypotension and 2) improves post-resuscitation cardiac function.

Methods:
Pigs (38kg) were randomized to: Sham (n=5), Sham + ALM (n=5), hemorrhage (n=11), and hemorrhage + ALM (n=9). Animals were subjected to pressure controlled hemorrhage at a target MAP of 35mmHg. After 90 min Ringers acetate and 20ml 7.5% NaCl ± ALM (Adenosine 0.23 mg/kg; Lidocaine 0.64 mg/kg; Mg2+ 0.4 mg/kg) was infused to maintain a target MAP of 50 mmHg (permissive hypotension). After 30min 75% of the shed blood was re-infused ± ALM (Adenosine 0.82 mg/kg; Lidocaine 1.66 mg/kg) and the pigs were observed for 6 hrs. Cardiac function was evaluated by pressure-volume (P-V) analysis.

Results:
In the ALM group 40% less fluid was required to maintain a MAP of 50mmHg for 30min (hemorrhage: 41.5ml/kg CI: 27.7-61.8 vs. ALM: 24.7ml/kg CI:19.4-31.5*). During permissive hypotension 7.5% NaCl ALM significantly increased end-systolic pressure by 27% (hemorrhage: 70 mmHg ± 3 vs. ALM: 89 mmHg ± 9*) and cardiac contractility by 64% (dP/dtmax) (hemorrhage: 2622 mmHg/sec ± 331 vs. ALM: 4301 mmHg/sec ± 262*). Treatment with ALM at blood infusion reduced whole body O2 consumption by 27% lasting 30 min into infusion (group difference p<0.05). In addition, systolic function after blood reinfusion, evaluated by the end-systolic P-V relationship and preload recruitable stroke work, was significantly improved in ALM vs. hemorrhage. Furthermore, ALM enhanced relaxation (dP/dtmin) during reperfusion (hemorrhage: -1578 mmHg/sec ± 103 vs. ALM -2178 mmHg/sec ± 189*).

Conclusion:
7.5% NaCl ALM reduced fluid requirements by 40% during permissive hypotension, improved cardiac function and reduced total body O2 consumption following severe hemorrhage. Administration of ALM is effective in minimizing fluid requirements and I/R injury following hemorrhage. (* p<0.05)
Abstract 46: Guidelines Changes and Improvement of Survival to Hospital Discharge After Out-of-Hospital Cardiac Arrest: A Meta-Analysis from the Literature
Authors: Savastano Simone , Klersy Catherine , Rordorf Roberto , Langord Karen , Vanni Vincenzo , Vicentini Alessandro , Petracci Barbara , Ballerini Luca , Chieffo Enrico , Poggio Luca , Striuli Laura , Landolina Maurizio , Oltrona Visconti Luigi , Schwartz Peter J
Published: April 2024

Introduction.
Every year 350.000 to 750.000 cases of cardiac arrest occur in the US and in Europe. Since 1974 seven editions of CPR-ECC guidelines have been published and many aspects have been changed. In particular more and more empahis has been given on CPR and the suggested compression to ventilation ratio has progressively been increased (5:1 before 2000, 15:2 from 2000 to 2005 and 30:2 after 2005). The aim of our study is to evaluate, based on a review of the literature, the impact of changes in guidelines on survival to hospital discharge after out of hospital cardiac arrest (OHCA).

Material and methods.
We searched PubMed for studies on “survival to hospital discharge after OHCA”. Mandatory inclusion criteria included the report of survival to hospital discharge in all patients regardless of presenting rhythm. All data were analyzed according to the year of inclusion: group 1 before 2000; group 2 between 2000 and 2005 and group 3 after 2005. Survival/mortality rates were computed for each group, together with their 95% binomial confidence interval (95%CI). In-hospital mortality rates were compared between groups by means of a group frequency weighted log linear model. Risk ratios (RR) and 95%CI were reported.

Results.
Among 558 studies retrieved, 45 met our inclusion criteria, with a total of 119,111 of OHCA patients evaluable (65,601 in group 1; 35,954 in group 2 and 17,556 in group 3). The mean call to response time was similar in the three groups: 7.9 ± 2.7 min,; 7.5 ± 2.3 min and 6.9 ± 2.0. min in group 1, 2 and 3, respectively. Survival to hospital discharge in the 3 groups was 6.2% (95%CI 6.0-6.4), 6.4% (95%CI 6.2-6.7) and 9.9% (95%CI 9.5-10.4), respectively (log linear model p<0.001). Specifically a significant decrease in risk of hospital death was observed in group 3 vs group 2 (RR 0.69 (95%CI 0.95-0.97, p<0.001), but not in group 2 vs group 1 (RR 1.00 (0.99-1.00, p=0.14).

Conclusion.
This quantitative review of the literature demonstrated that survival to hospital discharge after OHCA has significantly increased after 2005 guidelines changes. The cardio-centric revolution in CPR and in advanced care with more high quality CPR resulted in a 30% improvement in survival after OHCA.
Abstract 9665: PKA / CREB Pathway Initiates Endothelial and Hematopoietic Cell Differentiation Via Etv2 Induction
Authors: Yamamizu Kohei , Matsunaga Taichi , Katayama Shiori , Yamashita Jun K.
Published: April 2024

Kohei Yamamizu, 2011 Finalist and Presenting Author
Abstract 8129: A Novel Mutation in HERG Leading to an LQTS Overlap Syndrome
Authors: Shah Ravi , Zilinski Jodi , Abtahian Farhad , Das Saumya
Published: April 2024

Ravi Shah, 2011 Finalist and Presenting Author
Abstract 12938: A 26 Year Old Male with Exertional Cyanosis
Authors: Punnoose Lynn R , Weinsaft Jonathan
Published: April 2024

Lynn R Punnoose, 2011 Finalist and Presenting Author
Abstract 53: Decoding Twitter: What Does the Public Want to Know About Cardiac Arrest and Resuscitation?
Authors: Zhao Nina W , Bosley Justin C , Becker Lance , Asch David A , Merchant Raina M
Published: April 2024

Background:
Social media sites like Twitter are growing in popularity and offer new avenues to share and seek health information. Twitter may also serve as an important public health tool for experts to widely disseminate accurate information about cardiovascular health. The manner and extent of the public's information-seeking behavior however is unknown. To better understand public inquiries about resuscitation, we sought to characterize tweets with questions about cardiac arrest, CPR, and AEDs.

Methods:
A database of 53,971 tweets relating to resuscitation was created using a Twitter search engine for daily tweet downloads from April 19-May 22, 2011. Search terms were: AED, cardiac arrest, CPR, defibrillation, heart arrest, and resuscitation. Tweets containing nonsensical, non-English, non-sequitur, or irrelevant information were excluded (n=39,990). Remaining tweets were individually evaluated for information seeking questions.

Results:
Of 13,981 tweets with resuscitation-relevant content, 1% (162) had questions related to cardiac arrest/CPR/AED. Inquires were distributed across the study time period with a mean 4.8 questions daily. Several tweets, 21% (34/162) were cardiac arrest-related queries related to: symptoms, risk factors, prognosis, distinction from heart attack, treatment options, utility of abdominal compressions, and therapeutic hypothermia indications. Several tweets, 39% (63/162) were CPR-specific queries related to: definitions, guidelines, technique, certification classes (location, duration, and professional requirements), neonatal resuscitation, hyperventilation treatment, and accuracy of media portrayal of resuscitation. Additionally, 40% (65/162) of tweets were AED-specific queries related to: device safety, cost, purchasing advice, availability, proper use, effectiveness, and batteries.

Conclusion:
Twitter offers a novel venue for the public to ask questions regarding cardiovascular health. While few tweets were true information-seeking messages, they represent unique opportunities for expert intervention, education, and awareness. Future work in this field may aim to uncover how receptive users are to professional answers and healthcare education delivered via tweets.
Abstract 13986: Fatigue, Inflammation, and Projected Mortality in Heart Failure
Authors: Fink Anne M , Gonzalez Rosalia C , Lisowski Tadeusz , Pini Maria , Fantuzzi Giamila , Levy Wayne C , Piano Mariann R
Published: April 2024

Anne M Fink, 2011 Finalist and Presenting Author
Abstract 14949: Mechanisms for Human Atrial Fibrillation Initiation: Clinical and Computational Studies Implicating Repolarization Restitution
Authors: Krummen David E , Bayer Jason D , Ho Jeffrey , Ho Gordon , Mollerus Miriam R , Trayanova Natalia A , Narayan Sanjiv M
Published: April 2024

David E Krummen, 2011 Finalist and Presenting Author
Abstract 11544: MicroRNA-145 Targeted Therapy Reduces Atherosclerosis and Improves Plaque Stability
Authors: Shukla Praphulla , Lovren Fina , Pan Yi , Quan Adrian , Creighton Amie , Gupta Nandini , Yanagawa Bobby , Singh Krishna , Teoh Hwee , Verma Subodh
Published: April 2024

Praphulla Shukla, 2011 Finalist and Presenting Author
Abstract 56: Sodium Nitroprusside--Enhanced Cardiopulmonary Resuscitation Prevents Postresuscitation Left Ventricular Dysfunction and Improves 24-Hour Survival and Neurological Function in a Porcine Model of Prolonged Untreated Ventricular Fibrillation
Authors: Yannopoulos Demetris , Schultz Jason , Segal Nicolas , Kolbeck James , Caldwell Emily , Thorsgard Marit , McKnite Scott , Aufderheide Tom , Lurie Keith
Published: April 2024

Background:
Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 minutes of untreated ventricular fibrillation (VF) in a porcine model of cardiac arrest.

Methods:
Pigs (n=22) anesthetized with isoflurane underwent 15 minutes of untreated VF, were then randomized to 6 minutes of S-CPR (n=11) or SNPeCPR (n=11) followed by defibrillation. The primary endpoints were neurologic function as measured by cerebral performance category (CPC) score and left ventricular ejection fraction.

Results:
SNPeCPR increased 24-hour survival rates compared to S-CPR (10/11 versus 5/11, p=0.03) and improved neurological function (CPC score 2.5±1, versus 3.8±0.4, respectively, p=0.004). Left ventricular ejection fractions at 1, 4 and 24 hours after defibrillation were 72±11, 57±11.4 and 64±11 with SNPeCPR versus 29±10, 30±17 and 39±6 with S-CPR, respectively (p<0.01 for all).

Conclusions:
In pigs, after 15 minutes of untreated VF, SNPeCPR significantly improved 24-hour survival rates, neurologic function and prevented post-resuscitation left ventricular dysfunction.
Abstract 60: Dexmedetomidine Administration During CPR Improves Stroke Volume During the Early Postresuscitation Period
Authors: Badugu Srinivasarao , Shih Andre , Kaliki Venkata Giridhar , Haque Ikram , Zaritsky Arno , Udassi Jai P
Published: April 2024

Introduction:
Elevated sympathetic response after CPR worsens myocardial dysfunction and cardiac output. Dexmedetomodine has sympatholytic effects both in animal and human studies.

Hypothesis:
Dexmedetomidine given during CPR improves stroke volume (SV) after ROSC compared with standard CPR.

Methods
Sixteen anesthetized & ventilated (2 months old) farm pigs (UF Research Swine) of either sex were blindly randomized (8/group) after induction of ventricular fibrillation (VF; via direct right ventricular current) to receive either dexmedetomidine (2 mcg/kg) or placebo after the first minute of chest compressions per AHA CPR guidelines. Chest compressions were delivered at 100/min by a pneumatic compressor device (Thumper, Michigan instruments, USA) and 21% FiO
2
was used for ventilation. SV was measured at 15, 30, 60, 90 and 120 minutes after ROSC using a Pressure-Volume (P-V) catheter in the left ventricle (Millar instruments, Michigan, USA). Cardiac output was calculated from SV and heart rate. Outcome (mean±SD) was analyzed using mixed linear model (SAS Proc MIXED). We used an unpaired t-test for the differences between groups at each time point; p-value ≤0.05 was considered significant.

Results
Dexmedetomidine group had significantly higher stroke volume (% change from baseline) at 15 minutes (97±24 vs. 44±19,
p
=0.0006) and 30 minutes (87±26 vs. 51±21
p
=0.0153). CO (% change from baseline) was higher in Dex group at 15 minutes (141±53 vs. 61±23,
p
=0.0061) and at 30 minutes (115±44 vs. 55±17
p
=0.0122). SV and CO were higher, but not significantly after 30 minutes. The study group had significantly higher CO (% change from baseline) across all time points combined compared with the control group (89.3±6.14 vs. 60.1±7.15, p=0.0033). End-diastolic volume trended higher in Dexmedetomidine group but was not significant. HR was not different between the two groups.

Conclusions
Dexmedetomidine, when given during the initial cycle of chest compressions during CPR, increases SV and CO early post ROSC. Further studies are needed to evaluate the appropriate dose, continuous infusion and time of administration.
GPIHBP1, the Endothelial Cell Transporter for Lipoprotein Lipase
Authors: Young Stephen G.
Published: April 2024

The discovery, by Drs. Beigneux, Fong, and Young, of severe chylomicronemia in GPIHBP1-deficient mice reignited interest in the lipolytic processing of triglyceride-rich lipoproteins. GPIHBP1 is a glycophosphidylinositol-anchored protein expressed exclusively in capillary endothelial cells, and it binds lipoprotein lipase (LPL) avidly. GPIHBP1 has two noteworthy protein domains, an amino-terminal acidic domain and a cysteine-rich Lymphocyte antigen 6 (Ly6) domain, and both are important for binding LPL. The localization of GPIHBP1 in capillaries, along with its ability to bind LPL, initially prompted speculation that GPIHBP1 served as an LPL binding site within the capillary lumen (creating “a platform for lipolysis”). More recent studies have identified a second and more intriguing role for GPIHBP1—picking up LPL in the subendothelial spaces (where it is secreted by myocytes and adipocytes) and then transporting it across endothelial cells to the capillary lumen, where it acts to hydrolyze the triglycerides within the plasma lipoproteins. Over the past few years, significant progress has been made in defining the amino acids within LPL and GPIHBP1 residues that are important for GPIHBP1–LPL interactions. Also, the human genetics of chylomicronemia has come into sharper focus. Some cases of chylomicronemia in humans are caused by mutant GPIHBP1 proteins that lack the ability to bind LPL, and others are caused by mutant LPL proteins that lack the ability to bind to GPIHBP1. The discovery of GPIHBP1 as the LPL transporter is a significant development in our understanding of lipoprotein physiology, and one that should lead to a vastly improved understanding of triglyceride metabolism and hyperlipidemia.
Decoding the Cardiac Message
Authors: Dorn Gerald W.
Published: April 2024

Our understanding of the molecular underpinnings of cardiac development and stress-response has progressed non-linearly over the past 40 years. Preliminary observations that cardiac RNA content increases along with muscle mass in hypertrophy were followed in the 1980s by an explosion of information derived from the fruits of cDNA cloning: The use of individual gene-specific cDNA probes for spatio-temporal analysis of gene expression lead to the description of cardiac myosin and actin isoform mRNA regulation by thyroid hormone. Recombinant expression systems were developed as platforms for functional analyses of cDNA products. Assays of muscle-specific mRNAs after cellular manipulation revealed that intracellular proteins regulate gene transcription. The subsequent decades defined specific cis DNA elements and transactivating protein factors that reprogram individual cardiac genes in disease, and transcriptional profiling by microarray or RNA sequencing revealed genome-wide mRNA regulation under pathological conditions. However, the underlying mechanistic concepts about how mRNA expression is regulated did not change. Now, we are witnessing a second molecular revolution catalyzed by the recent observation that cytoplasmic microRNAs directly regulate mRNAs. Whereas transcriptional regulation is more “on” or “off” for a single gene, a single microRNA can fine-tune entire biological pathways according to physiological demand by partially suppressing or destabilizing multiple functionally related mRNAs. Concomitant transcriptional regulation of microRNAs and their mRNA targets in cardiac disease enhances diversity of response, but deconvoluting these interactions is a challenge to defining the role of microRNAs in heart disease. Understanding the determinants of microRNA-mRNA targeting will accelerate rational development of microRNA-based therapeutics.
Understanding Ventricular Remodeling after Correction of Mitral Regurgitation: Thinking Volumetrically
Authors: Schaff Hartzell V.
Published: April 2024

Early after correction of mitral valve (MV) regurgitation, systolic function of the left ventricle (LV) declines, but the underlying mechanisms of this phenomenon are unknown. Most studies in this area have analyzed LV function at one week postoperatively or later. In a retrospective study from our Clinic, Enriquez-Sarano et al. reported a decline in LV ejection fraction (EF) from 62% to 52% (
P
<0.001) in 217 patients with organic mitral regurgitation who were studied within the first year after MV replacement or repair. This decline was due to decreased left ventricular end-diastolic dimension (LVEDD) and minimal change in left ventricular end-systolic dimension (LVESD). Surgical investigators have compared the outcomes for different techniques of MV replacement and studies indicate that decline in EF may be mitigated by chordal preservation.

It has been suggested that early postoperative measurements of cardiac geometry and function are confounded by the effects of global ischemia, reperfusion, and myocardial protection. Indeed, some clinicians have suggested that reduced EF early after MV repair results from myocardial dysfunction that, in turn, is related to poor myocardial protection. In addition, cardiac loading conditions change dramatically early after operation.

We speculated that a postoperative decline in LV systolic indexes (eg, EF, FAC, and FS) may be interpreted as a volumetric adjustment of the heart to the correction of mitral regurgitation rather than as postoperative LV dysfunction due to impaired myocardial contractility, and clinical studies support this hypothesis. Soon after MV repair, the LV remodels gradually. Very early after correction of mitral regurgitation, the LVESD increases, preventing an acute increase in forward stroke volume. Within the next few postoperative days, the LVEDD begins to decrease and the LVESD changes accordingly to maintain a normal forward stroke volume; the remodeling occurs when neurohumoral mechanisms of the body adapt to the new hemodynamic milieu. This progression of remodeling may explain why some investigators have observed unchanged LV systolic and decreased diastolic size on the first postoperative echocardiogram about a week after MV repair.
Abstract 61: A Novel Electrical Therapy for Postshock PEA in a Porcine Model
Authors: Weng Yinlun , Quan Weilun , Freeman Gary , Wu Xiaobo , Ye Sen , Chen Wei , Sun Shijie , Tang Wanchun
Published: April 2024

BACKGROUND:
Chest compression (CC) is currently recognized as the only effective intervention for the treatment of shock induced pulseless electrical activity (PEA). This study was designed to test a new form of therapy, packet electrical therapy (PET), for post shock PEA in a porcine model using medium energy electrical pacing. The main objective was to compare hemodynamic responses between the PET and the standard CC.

METHODS:
In 12 domestic pigs weighing 22-24kg, ventricular fibrillation (VF) was electrically induced and untreated for 2 to 7 minutes before delivering shock to induce post shock PEA with peak aortic pressures below 40 mm Hg. Once the PEA was induced, animals received 15 sec PET followed by 45 sec standard CC, and followed by 15 sec PET combined with the standard CC in sequence. If animals were resuscitated after the study sequence, after 30 minutes recovery, PEA induction and the study sequence were repeated. PET consisted of a train of narrow pulses with the amplitude of 2 amperes and the total duration of 200 ms, the depth of standard CC was maintained at 2 inches of the anterior posterior diameter of the thorax.

RESULTS:
A total of 35 qualified PEA events from 9 animals were included in the analyses as shown in the table:

CONCLUSION:
No significant differences were detected between coronary perfusion pressures for PET as compared to standard chest compressions. Both aortic and right atrial diastolic pressures were significantly increased with PET.
Abstract 66: The Duration of Asystole Before Return of an Organized Rhythm or Spontaneous Circulation After Defibrillation
Authors: Pierce Ava , Owens Pamela , Idris Ahamed H
Published: April 2024

Background:
Defibrillation success has been traditionally defined as termination of ventricular fibrillation five seconds after the shock. The current American Heart Association guidelines for Cardiopulmonary Resuscitation (CPR) recommend that chest compressions resume immediately after defibrillation and to perform rhythm and pulse checks after 5 cycles of CPR. Few studies have reported the duration of asystole after defibrillation before return of an organized rhythm or return of spontaneous circulation (ROSC).

Objective:
To describe the duration of asystole before return of an organized rhythm or ROSC after defibrillation during out-of-hospital (OOH) non-traumatic cardiac arrest.

Methods:
This observational study analyzed Dallas-Fort Worth ROC site data collected in the Resuscitation Outcomes Consortium (ROC) Epistry database. We reviewed monitor-defibrillator recordings of patients who were defibrillated for ventricular fibrillation or pulseless ventricular tachycardia during OOH cardiac arrest. We analyzed the duration of asystole after defibrillation before return of an organized rhythm or ROSC. An organized rhythm was defined as similar QRS complexes that produce a consistent rhythm without a palpable pulse.

Results:
A total of 176 patients were defibrillated after OOH cardiac arrest from November 2009 to April 2011. Mean age was 61 ± 17 years and 66.6% were male. The mean interval of asystole after defibrillation was 56 ± 144 sec (0 - 1098 sec), median 6 sec (IQR 29). The mean time to return of an organized rhythm after defibrillation was 64 ± 157 sec, median 7 sec (IQR 26). The mean time to ROSC after defibrillation was 280 ± 320 sec, median 136 sec (IQR 445). ROSC occurred in 51 (29%) patients and 16% survived to hospital discharge. The defibrillation energy that resulted in ROSC were as follows: twenty-nine at 200 Joules, eight at 300 Joules, nine at 360 Joules, one at 70 Joules, and 4 in the Emergency Department.

Conclusion:
The post-shock duration of asystole before return of an organized rhythm or ROSC is longer than 30 seconds in 25% of patients. Our findings support the recommendation to immediately resume chest compressions following attempted defibrillation and to continue CPR for two more minutes before checking the rhythm.