bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract 18646: The Dynamic Relationship Between GRK2 and NOS/NO Critically Determines Cardiac Ischemia/Reperfusion Injury
Authors: Huang Z. Maggie , Gao Erhe , Shang Xiying , Tian Xufan , Qiu Gang , Chuprun J Kurt , Hayashi Hiroki , Hess Douglas T , Lefer David J , Stamler Jonathan S , Koch Walter J 
Published: April 2024

Background and Aim
s: G protein-coupled receptor kinase 2 (GRK2) and endothelial nitric oxide synthase (eNOS) play key roles in cardiac signaling and function. Increased GRK2, seen in injured myocardium, causes increased cell death and injury after ischemia while reciprocally, eNOS/NO exerts protection. A link between these two systems occurs as GRK2 can be regulated via S-nitrosylation (SNO) at Cys340, which inhibits its activity. Alternatively, increased GRK2 activity inhibits NO in the heart. The aim of this study was to determine whether there is a dynamic interaction between cardiac GRK2 and eNOS/NO.

Methods: We investigated a direct interaction between GRK2 and eNOS in cultured myocytes and hearts. Cardiac-specific transgenic mice overexpressing GRK2 (Tg-GRK2) and mice with expression of the GRK2 inhibitor βARKct (Tg-βARKct) were used to create hybrid mice with concurrent modulation of eNOS. Finally, we created novel knock-in mice where all endogenous GRK2 was a mutant form (Cys340Ser) resistant to SNO regulation. All mice were characterized basally and subjected to ischemia/reperfusion (I/R) injury and infarct size and cardiac phenotypes determined.
Results: 1). Co-immunoprecipitation discovered an interaction between GRK2 and eNOS in cardiac tissue, which was significantly increased in the ischemic heart. 2). TgGRK2/TgeNOS hybrid mice showed significantly reduced infarct size and improved function post I/R compared to Tg-GRK2 mice. Protection offered by βARKct was reversed in mice without eNOS. 3). SNO-GRK2 was increased by isoproterenol and GSNO in WT mice but was not observed in GRK2-C340S mice. 4). Interestingly, GRK2-C340S mice exhibited significantly larger injury post I/R compared to WT mice with decreased cardiac dysfunction. GSNO treatment reduced infarct size in WT mice but had no effects in GRK2-C340S mice. Also, pre-treatment with the NOS inhibitor L-NAME increased infarct size in WT mice but not in GRK2-C340S mice.

Conclusions:
Our data demonstrates a unique relationship between GRK2 and NO signaling in the heart, which has direct implications for mechanisms of cardiac injury. This includes the demonstration that GRK2 is a nodal pro-death kinase after I/R injury and its SNO is a requirement for NO-mediated cardioprotection.
Abstract 18805: Vorapaxar, A Platelet Thrombin-Receptor Antagonist, in Patients with Non-ST-Segment Elevation Acute Coronary Syndrome Undergoing Percutaneous Coronary Intervention: Results from the TRACER Trial
Authors: Valgimigli Marco , Tricoci Pierluigi , Huang Zhen , Aylward Philip , Armstrong Paul , White Harvey , Widimsky Petr , Harrington Robert , Cequier Angel , Ziada Khaled , Chen Ming-Fong , Chen Edmond , Lokhnygina Yuliya , Wallentin Lars , Strony John , Mahaffey Kenneth , Moliterno David 
Published: April 2024

Objectives: Evaluate the effects of protease-activated-receptor 1 antagonist vorapaxar in NSTE ACS pts undergoing PCI during index hospitalization.
Methods: This prespecified analysis of a post-randomization subgroup evaluated the effects of vorapaxar compared with placebo among TRACER pts undergoing PCI, focusing on implanted stent type (drug-eluting stent [DES] vs bare metal stent [BMS]).
Results: Among 12,944 TRACER pts, 7479 (58%) underwent PCI during index hospitalization; 1576 (44.4%) of vorapaxar pts and 1484 (42.1%) of placebo pts received exclusively BMS implantation. During the treatment period with vorapaxar, the median duration of thienopyridine therapy was 133 (47-246) days with BMS and 221 (88-341) days with DES. At 1 yr, the primary endpoint (CV death, MI, stroke, recurrent ischemia with rehospitalization, or urgent coronary revascularization) occurred in 10.4% of pts with vorapaxar vs 10.6% of pts with placebo (HR 0.96; 95% CI 0.83-1.10). The key secondary endpoint (CV death, MI, stroke) occurred in 6.8% with vorapaxar and 7.3% with placebo (HR 0.89; 95% CI 0.75-1.05). A trend of interaction was noted on CV death, MI, and stroke between treatment and type of implanted stent, with pts receiving BMS showing a relatively greater effect from vorapaxar (Figure). GUSTO moderate/severe bleeding was overall increased with vorapaxar with no statistical interaction, although the relative increase appeared less with BMS (HR 1.27; 95% CI 0.85-1.90) than with DES (HR 1.70; 95% CI 1.14-2.53).
Conclusions: In this post-randomization subgroup analysis, the efficacy of vorapaxar among PCI pts is consistent with the overall TRACER results. The duration of dual antiplatelet therapy was shorter with BMS than with DES, and a noteworthy signal of increased efficacy and less bleeding liability was noted in BMS pts. These results point to further research opportunities to evaluate the potential clinical role of vorapaxar.
Abstract 19: Cardiopulmonary Resuscitation by Bystanders with Chest Compressions Only for Children with Witnessed Out-of-Hospital Cardiac Arrest
Authors: Shimizu Naoki , Ohta Kunio , Nitta Masahiko , Yonemoto Naohiro , Nonogi Hiroshi , Nagao Ken , Kimura Takeshi , Japanese Paediatric Resuscitation Study (PReSS) Group  , JCS-ReSS group  
Published: April 2024

Background: Conventional cardiopulmonary resuscitation (CPR) is a barrier to bystanders including parents doing CPR for children. Particularly mouth-to-mouth ventilation has been considered to be difficult to teach and perform. Several clinical studies have shown the efficacy of bystander CPR by chest compression only (CC-only) for adults, but not yet stated enough for children.
Methods: In a nationwide out-of-hospital cardiac arrest (OHCA) registration from 2005 to 2010, we enrolled 11,417 children aged less than 18 years old. Data collected include age, etiology, ECG wave form, type of CPR, and neurological outcome. Favorable outcome was defined as cerebral performance category 1 or 2.
Results: 3,486 (31%) children with OHCA were described as cardiac etiology, and 7,931 (69%) as non-cardiac. VF/pulseless VT (VF/pVT) in 546 (5%) cases, PEA in 1,668 (15%), and asystole in 8,168 (71%). 3,041 (27%) cases received conventional CPR, 2,421 (21%) received CC-only CPR, and 5,507 (48%) were given no CPR. Within 2,808 (25%) children with witnessed citizen bystanders, 706 (25% of 2,808) received conventional CPR and 577 (21% of 2,808) received CC-only CPR, but outcome was not available in 69 cases. Any CPR comparing with no CPR (8.5% [463/5,462] vs 3.1% [168/5,507]; OR 2.78, 2.32-3.32), or conventional CPR comparing with CC-only (11% [329/3,041] vs 5.5% [134/2,421]; OR 1.95, 1.59-2.40) showed higher favorable outcomes. However, analysis in children with witnessed citizen bystanders revealed no difference on favorable outcome between conventional CPR and CC-only CPR (9.0% [60/668] vs 7.5% [41/546]; OR 1.22, 0.80-1.83). In each waveform group (VF/pVT; 32% [38/118] vs 29% [25/86]; OR 1.11, 0.62-1.97, PEA 7.1% [11/156] vs 6.3% [9/142]; OR 1.11, 0.45-2.76, Asystole 3.1% [11/353] vs 2.2% [7/318]; OR 1.42, 0.54-3.69), even excluding infants (11% [56/514] vs 8.0% [35/438]; OR 1.36, 0.88-2.11), indicated same trends.
Conclusion: CC-only CPR by witnessed citizen is equally effective for children who have witnessed OHCA, comparing with conventional CPR. Enhancement of citizen bystander CPR including children with uniform BLS algorithm is reasonable, and need to be enriched further to diminish paediatric OHCA events without bystander CPR.
Abstract 19155: The Impact of Expeditious Management of Perioperative Myocardial Ischemia in Patients Undergoing Isolated Coronary Artery Bypass Surgery
Authors: Davierwala Piroze , Verevkin Alexander , Leontyev Sergey , Misfeld Martin , Borger Michael A , Mohr Friedrich W 
Published: April 2024

Objective: To analyze the effect of immediate treatment of perioperative myocardial ischemia due to early graft failure in patients undergoing coronary artery bypass surgery (CABG).
Patients and methods: Between January 2004 and December 2010, 7489 patients underwent isolated CABG at our institution. All patients (n=427, 5.7%) who showed evidence of perioperative myocardial ischemia (PMI) underwent emergent coronary angiography. PMI was characterized by an isoenzyme ratio of creatinine phosphokinase (CK/CK-MB) > 10% and/or new ST-segment changes and/or recurrent episodes of ventricular tachycardia or fibrillation and/or hemodynamic deterioration with new regional wall motion abnormalities on echocardiography. One thousand and thirteen grafts and 1131 distal anastomoses were examined angiographically.
Results: One hundred and seventy-six patients had a normal postoperative coronary angiography. Two hundred and fifty-one patients had stenoses or occlusions of 372 grafts. Revision CABG (group A) or percutaneous coronary intervention (PCI) (group B) was performed in 130 (51.8%) and 31 (12.4%) patients with graft stenosis or occlusion, respectively. Conservative therapy was implemented in 92 (36.6%) patients (group C). In-hospital mortality was 8.4% and 2.9% in patients with and without PMI (p < 0.001). In the former group, in-hospital mortality was 10.4% and 5.7% in patients with and without graft failure, respectively (p=0.087). There was no difference in early and long-term survival between the 3 treatment groups for graft failure (p=0.8). On the other hand, 1- and 5-year survival in patients with no PMI (93.3±0.03% and 83.6±0.05%, respectively) was significantly better than those with PMI (92.3±0.1% and 82.4±0.2%, respectively) [p<0.001 log rank]. When in-hospital mortality was excluded, there was no difference (p=0.1) in long-term survival between patients with and without perioperative myocardial ischemia.
Conclusions: Perioperative ischemia is associated with increased in-hospital mortality in patients undergoing isolated coronary bypass surgery. Expeditious treatment of bypass graft stenosis or occlusion results in similar long-term survival to non-ischemic patients in hospital survivors.
Abstract 20: Bystander Cardiopulmonary Resuscitation with Chest Compressions Only According to Dispatcher Telephone Instruction Status
Authors: Nagao Ken , Tachibana Eizo , Nishikawa Kei , Yagi Tukasa , Yonemoto Naohiro , Takayama Morimasa , Shirai Shinichi , Nonogi Hiroshi , Kimura Takeshi 
Published: April 2024

BACKGROUND
The 2010 AHA guidelines for cardiopulmonary (CPR) recommended that untrained lay rescuers should continue chest compression-only CPR under dispatcher-telephone CPR instruction and trained lay rescuers should continue conventional CPR if he or she is able to perform rescue breaths. We assessed the effect of bystander CPR according to dispatcher-telephone CPR instruction status.
METHODS
From the data of the All-Japan Utstein Registry, a prospective, nationwide, population-based registry of out-of-hospital cardiac arrest, we extracted the adult patients with bystander-witnessed out-of hospital cardiac arrest due to cardiac etiology, and divided into groups according to the dispatcher-telephone CPR instruction status, inclusive of CPR techniques. The primary endpoint was 30-day favorable neurological outcome after cardiac arrest.
RESULTS
Of the 113,624 patients who met the inclusion criteria, 45,565 received dispatcher-telephone CPR instruction and 68,059 did not. Higher proportions in the instruction group than in the no instruction group were the performance of bystander CPR (chest-compression only CPR or conventional CPR) (68% [30,929/45,565] vs. 31% [20,900/68,059], p<0.0001), especially that of chest-compression only CPR (46.2% [21,032/45,565] vs. 17.0% [11,541/68,059], p<0.0001). Although frequencies of 30-day favorable neurological outcome in the instruction group were significantly lower than in the no instruction group for the whole cohorts (4.8% vs. 5.5%, p<0.0001) and the subgroups of patients receiving bystander CPR (5.7% vs. 7.8%, p<0.0001), chest-compression only CPR was equivalent or superior to conventional CPR in each group in terms of neurological benefit (5.7% vs. 5.9% in the instruction group, p=0.57, and 8.2% vs. 7.3% in the no instruction group, p=0.03). Among patents receiving bystander CPR, adjusted odds ratios of favorable neurological outcome were 1.2 (95% CI; 1.1 to 1.3) after no instruction group, and 1.1 (1.0 to 1.2) after chest-compression only CPR.
CONCLUSIONS
Bystander chest-compression only CPR was not inferior to conventional CPR in terms of neurological benefits, and dispatcher-telephone CPR instruction increased the performance rate of chest-compression only CPR.
Abstract 206: Intravenous Lipidic Oxygen Microparticles Improve Arterial Oxygen Content and Cerebral Oxygen Delivery During CCC-Only CPR
Authors: Kheir John , Thomson Lindsay , Danforth Lauren , Cronin Julie , Dowling Catherine , Elder Jennifer , Velazquez Luis , Nadkarni Vinay , Berg Robert , McGowan Francis 
Published: April 2024

Background: Although the effectiveness of CCC-only CPR is well-established, the benefits of adjuncts to further improve systemic oxygen delivery merit study. Oxygen gas can be encapsulated within injectable microparticles, or lipidic oxygen microparticles (LOMs), which transfer oxygen rapidly to the bloodstream within seconds of intravenous injection. The purpose of this study was to determine whether LOMs increase arterial oxyhemoglobin concentration, oxygen delivery and affect ROSC in a porcine model of experimentally-induced VF employing CCC-only CPR.
Methods: Yorkshire swine (30 kg) were sedated with Ketamine and Xylazine for tracheal intubation and placement of femoral venous and arterial catheters. VF was induced and animals were immediately extubated and treated as shown in Fig 1A. CPR depth, rate, and leaning was guided in all animals with real time feedback from the monitor/defibrillator. Animals with shock-refractory VF were randomized to treatment with standard ACLS therapy with (n=5) or without (n=3) intravenous LOMs (Fig 1A).
Results: Relative to controls, animals treated with LOMs in addition to standard ACLS therapy exhibited a significantly increased arterial oxyhemoglobin saturation during LOM administration (P<0.0001, 2 way ANOVA, Fig 1B), a higher cerebral NIRS during LOM administration (P<0.0001, linear regression, Fig 1C), a higher diastolic blood pressure during LOM administration (P<0.0001, linear regression, Fig 1D), and a trend towards increased incidence of ROSC (P=0.36, Fig 1E). CPR quality (depth and rate) was similar between groups (P=1.00).
Conclusion: LOMs may increase arterial oxygen content, cerebral oxygen delivery during CCC-only CPR, and may be a useful adjunctive therapy in non intubated patients with out-of-hospital cardiac arrest.
Abstract 238: Substantial Incomplete Chest Recoil Occurs During CPR in a Pig Model
Authors: Aelen Paul , Ordelman Simone , Paulussen Igor , Noordergraaf Gerrit-Jan , Woerlee Pierre 
Published: April 2024

INTRODUCTION
The 2010 AHA / ERC Guidelines recommend compression depths of 5-6 cm. However, the neutral sternal position is assumed to remain unchanged. Changes in chest wall or lungs might cause incomplete chest recoil, altering the effect of 5-6 cm as a percentage of chest diameter. This could induce injury and affect the optimal compression depth. We investigated the hypothesis that incomplete chest recoil occurs during CPR in a pig model and that the speed at which this occurs changes with prolonged CPR. The incomplete chest recoil, or chest molding is a process of change, not a limitation to re-expansion caused by “leaning” or partial compression relaxation.
MATERIAL AND METHODS
Fourteen Yorkshire pigs with an average AP diameter of 20 cm were anesthetized, placed in dorsal recumbency, and ventricular fibrillation (VF) induced. After 90 s of VF, a specially made, proprietary servo controlled automated CPR device was used to deliver compressions of 5 cm depth at various frequencies (80-120 cpm) and duty cycles (40-60%). The plunger position (and unstressed sternal position) was determined at the start of each compression by the servo system. The position of the compression plunger (and thorax) was measured at a sample frequency of 250 Hz. An altered position at the start of a new compression is called the molded position.
RESULTS
In the 14 animals, chest molding occurred with an average initial rate of 0.34 ± 0.12 mm per compression. The average chest molding after 100 compressions was 17.4 ± 3.6 mm. After 21 minutes the average molding was 29.2 ± 10.3 mm with an average molding rate of -0.02 ± 0.04 mm/compression. The moulding curve shape was logarithmic. Initial compression depth was approximately 25% of AP diameter, increasing to 30% after 21 minutes CPR due to chest molding.
CONCLUSION
In conclusion, the molding magnitude was substantial. After initiation of CPR, chest molding occurs quickly, the rate slowing but never stopping, until compressions are stopped. The results could be extrapolated to humans but may be less pronounced due to a more vertical rib construction. Implications on CPR quality and injury need further investigation. Nevertheless, chest molding should be considered in the instructions for compression depth.
Abstract 290: Endothelial Dysfunction in a Rat Model of Asphyxia-Induced Cardiac Arrest
Authors: Troelsen Thomas T , Granfeldt Asger , Tønnesen Else , Simonsen Ulf 
Published: April 2024

Background: Altered vasoreactivity and elevated markers of endothelial activation are found following cardiac arrest (CA) and resuscitation. However, it is unknown whether the described altered vasoreactivity reflects influence from humoral factors, affection of the underlying smooth muscle or a change in the endothelium itself. Furthermore, it is unknown how the inflammatory markers correlate to endothelial function.
The aim of the present study was to assess endothelial function and the relation to plasma markers of inflammation and adhesion, CA and resuscitation.
Methods: Male Sprague Dawley rats underwent 5 min. of asphyxia-induced CA and subsequent resuscitation. After return of spontaneous circulation (ROSC) animals were euthanized after 30 min. or 2 hrs. Sham operated animals were used as controls. At the end of the experiment blood was drawn and analyzed for IL-1β, IL-6, IL-10, TNF-α, ICAM-1, VCAM-1, VEGF-α, vWF and sP-Selectin. Segments of the Left coronary artery (LCA) and mesenteric resistance arteries were mounted in microvascular myographs. Concentration-response curves for acetylcholine (ACH), NS309, and sodium nitroprusside where obtained.
Results: LCA-segments exhibited an impaired vasodilation to ACH after 30 min. of ROSC as CA animals dilated to a max of 66 ± 2 vs. 94 ± 8% in the sham group (Mean ± SE; P=0.0014). After 2 hrs. of ROSC vasoreactivity was comparable to sham groups for all drugs tested. The mesenteric arteries exhibited a larger response to NS309 after 2 hrs. of ROSC compared to 2 hr. sham (logEC50 ± SE: 0.43 ± 0.05 vs. 1.85 ± 0.23 µM; P<0,001). Levels of sP-selectin, vWF and sVCAM-1 were elevated in both CA groups vs. sham groups, with no correlation to vasoreactivity.
Conclusion: Endothelium-dependent ACH-induced nitric oxide (NO)-mediated vasodilation was blunted in LCA segments in the early post-resuscitation phase, NS309-induced endothelium-derived hyperpolarizing factor (EDHF)-mediated vasodilation was enhanced in mesenteric resistance arteries in the intermediate post-resuscitation phase. There was no relation of vasoreactivity to plasma markers of adhesion and inflammation. The altered vascular reactivity may explain impaired coronary flow and hypotension in the restitution phase after cardiac arrest.
Abstract 318: Potential Primary Prevention Implantable Cardioverter-Defibrillator Patients Lack Understanding, Want More Information and Are Willing to Reconsider Implant Refusal
Authors: Singh Narendra , Hall Erin , Lucas Essy , Chandra Sandeep , Song David , Yan Linda , Suh David , Dorsey Anthony , Ramamurthy Suresh 
Published: April 2024

Background:
Underutilization of ICD’s for primary prevention of sudden cardiac death has been previously reported in our practice. Factors leading to acceptance or refusal of device implant have not been well studied.

Method:
Prospective standardized interview and use of a 1-10 rating scale of randomly selected heart failure (HF) pts in a suburban outpatient cardiology practice.

Results:
Of the 533 HF pts identified with an ejection fraction of <35%, we randomly interviewed 50. Of these 54% were Caucasian (C), 36% African American (AA), 10% Asian (A). 29 pts (58%) accepted an ICD and 21 pts (42%) refused, the “no ICD” group. The mean age was 62+11 yrs, The mean EF was 24+7%. No significant differences in patient demographics, cardiac risk factors, HF medications or baseline labwork was seen.

Comparing ICD pts to no ICD pts - in both groups understanding of HF was poor, 4.5 on a scale of 1-10. The no ICD pts had less understanding of ICD purpose p<0.0003 , were less likely to have been given written ICD information (71 vs 38%, p=0.02) and were less likely to recall a recent discussion on the topic of ICD’s (52%). In both groups quality of life was more important than quantity 7.7+3 out of 10. Although 93% were Christian, religious belief (3.3+3 out of 10) and cultural values (3.2+3 out of 10) did not play a major role in decision making. Both group felt they had great access to health care resources and physicians (8.5+2 out of 10). Only 2 (7%) of ICD pts would not accept an ICD again, while 18 no ICD (86%) pts would now reconsider implant, p<0.001
Women were less likely to be married 26 vs 63%, p=0.02. A pts were younger than C, 56 vs 66 yrs, p=0.04. AA pts had less understanding of low EF vs C, p=0.02 and trended towards having less access to best medications p=0.1.

Conclusions:
Our qualitative study suggest that underutilization of ICD’s for primary prevention of SCD may in part be related to limited communication and poor understanding of HF, sudden death, and the devices. Furthermore the majority of pts initially refusing a device are willing to reconsider implant. These findings, with further validation, offers a potential approach to improving ICD underutilization in these high risk patients.
Abstract 80: Infliximab Is Superior to Etanercept for the Treatment of Postresuscitation Myocardial Dysfunction in a Swine Model of Ventricular Fibrillation
Authors: Youngquist Scott T , Niemann James T , Shah Atman P , Thomas Joseph L , Rosborough John P 
Published: April 2024

Introduction: Infliximab, a monoclonal antibody directed against the inflammatory cytokine TNF-α, has been shown to attenuate the myocardial dysfunction and hemodynamic decompensation associated with post-cardiac arrest syndrome. The aim of this study was to compare the effects of etanercept, a TNF-α receptor antagonist, to infliximab in a swine model of ventricular fibrillation (VF).
Methods: Under general anesthesia, VF was induced electrically in domestic swine (n=30). After 7 minutes of VF, standard ACLS resuscitation was performed. Animals achieving return of spontaneous circulation (ROSC) were randomized to immediately receive infliximab (5 mg/kg, n=10) or etanercept (0.3 mg/kg [4 mg/m2], n=10) or vehicle (250 mL normal saline [NS], n=10) and LV function and hemodynamics were monitored for 3 hours.
Results: Following ROSC, mean arterial pressure (MAP), stroke work (SW), and LV dP/dt fell from prearrest values in all groups. However, at the 30 minute nadir, infliximab-treated animals had higher MAP than either the NS group (difference 14.4 mm Hg, 95% confidence interval [CI] 4.2-24.7) or the etanercept group (19.2 mm Hg, 95% CI 9.0-29.5), higher SW than the NS group (10.3 gm-m, 95% CI 5.1-15.5, Figure) or the etanercept group (8.9 gm-m, 95% CI 4.0-14.4) and greater LV dP/dt than the NS group (282.9 mm Hg/sec, 95% CI 169.6-386.1) or the etanercep group (228.9 mm Hg/sec, 95% CI 115.6-342.2).
Conclusions: In conclusion, only infliximab demonstrated a beneficial effect on post cardiac arrest hemodynamics and LV function in this swine model. Etanercept was no better in this regard than saline.