bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P85: Out-of-hospital Cardiac Arrests With Extracorporeal Cardiopulmonary Resuscitation In Japan: Systematic Literature Review
Authors: Sakamoto Tetsuya , Asai Yasufumi , Nagao Ken , Tahara Yoshio , Atsumi Takahiro , Morimura Naoto , Nara Satoshi 
Published: July 2021

Background: In Japan, extracorporeal cardiopulmonary resuscitation (ECPR) became popular for cardiac arrest patients who resist conventional advanced life supports. Regardless of many clinical experiences, there has been no previous systematic literature review.
Methods: Case series, reports and proceedings of scientific meeting about ECPR for out-of-hospital cardiac arrest written in Japanese between January 1, 1983 and July 31, 2007 were collected with Japana Centra Revuo Medicina (medical publication database in Japan) and review by experts. The outcome and characteristics of the patients were investigated, and the influence of publication bias of the case series study was also examined by the Funnel Plot method.

Results: There were 951 out-of-hospital cardiac arrest patients who received ECPR in 92 reports (including 59 case series and 33 case reports) during the period. The average of age was 38.1 (4 – 88) years old and 76.1% was male. Three hundreds and eighty-one cases (40.1%) were arrests of cardiac etiology, and 212 were non-cardiac (22.3%). The cause of arrest was not described in other 37.6%. Excluding reports for only one case, weighted survival rate at discharge of 792 cases those were clearly described the outcome was 39.5±10.0%. When the relationship between the number of cases and the survival rate at discharge in each 59 case series study was shown in figure

by the Funnel Plot method, the plotted data presented the reverse-funnel type that centered on the average of survival rate of all.

Conclusions: The influence of publication bias of previous reports in Japan was relatively low. ECPR can greatly contribute to improve the outcome of out-of hospital cardiac arrests.
Abstract P97: Standardized Post Resuscitation Care including Therapeutic Hypothermia for Patients with Non-VF Arrests
Authors: Tomte Oystein , Draegni Tomas , Jacobsen Dag , Mangschau Arild , Sunde Kjetil 
Published: July 2021

Introduction: Whether therapeutic hypothermia (TH) improves survival after out-of-hospital cardiac arrest (OHCA) with initial asystole (AS) or pulseless electrical activity (PEA) is still controversial. At our hospital, revived OHCA patients follow the same standardized post resuscitation care protocol, if active treatment is desired. This includes TH, irrespectively of initial rhythm. Thus, we wanted to report the outcome for our OHCA patients of non-VF origin.
Methods: Since September 2003 all OHCA patients admitted to our hospital have been registered in a database. All patients with initial AS or PEA admitted to the Intensive Care Unit (ICU), or ward, between September 2003 and July 2007 were included. Favorable outcome is defined as a Cerebral Performance Category (CPC) of 1–2.
Results: Altogether 58 patients, all comatose, with a median age of 55 (range 19 –90 years), were registered. Cardiac etiology was present in 24 patients (41%), half of which had a myocardial infarction. Among the 34 patients (59%) with non-cardiac etiology, 15 were intoxications (44%), seven had asphyxia after respiratory failure (21%), five had suffered a cerebral event (15%), three drowned (9%), one had a pulmonary embolism (3%), and three causes remained unidentified. Overall, 37 patients (67%) were treated with TH; 16 (43%) received external cooling (Arctic Sun, Medivance), 13 (35%) endovascular cooling (Coolgard, Alsius Corporation) and eight (22%) other external cooling, all methods combined with initial ice cold fluids/ice packs. Median time in ICU was three days (range 0 –19 days). Eleven patients (19%) were discharged alive from hospital (cardiac etiology in four, 36%). Nine patients (16%) had a favorable outcome, and two patients (3%) had CPC 3.
Conclusion: After implementation of standardized post resuscitation care including TH, we found a 16% favorable survival among those admitted after non-VF OHCA, demonstrating a survival potential also for these patients.
Abstract P112: Precordial Thump Ineffective in Terminating Ventricular Fibrillation but May Have a Role in Asystole
Authors: Madias Christopher , Maron Barry J , Alsheikh-Ali Alawi A , Murphy Barbara , Egerhei Lara , Mark Estes N. A. , Link Mark S 
Published: July 2021

BACKGROUND. The efficacy of the chest thump in cardiac arrest is controversial. In an animal model of cardiac arrest we assess the efficacy of precordial thump in ventricular fibrillation (VF) and asystole.
METHODS. Under general anesthesia, 10 swine were induced to VF using a RV pacing lead and an AC fibrillator. In random order, animals received chest thumps with a 30 or 40 mph lacrosse ball or a chest thump with a fist. If VF continued after 3 thumps, animals were externally defibrillated. All animals underwent 6 VF inductions and received a total of 18 chest thumps; 2 sets of 3 thumps each with a fist, 30 mph, and 40 mph lacrosse balls. If asystole followed defibrillation, chest thumps with a fist were given to induce premature ventricular contractions (PVCs) until resumption of sinus rhythm. LV pressures of all thumps were recorded.

RESULTS. None of the 180 chest thumps terminated VF. The LV pressure generated by thumps during VF was 263 ± 52 mmHg for manual thumps, 392 ± 179 mmHg for 30 mph thumps, and 616 ± 182 mmHg for 40 mph thumps (p<0.001). All VF episodes were terminated by a 200J shock. Defibrillation was followed by asystole after 46/60 (77%) of VF inductions. During asystole, 1533/1856 (83%) chest thumps induced PVCs. LV pressure was higher for thumps that induced PVCs than those that did not (113 ± 27 vs 75 ± 23 mmHg, p<0.001). For each 10 mmHg rise in LV pressure, the OR of inducing a PVC was 1.9 (95% CI 1.8 –2.1; Figure

).

CONCLUSIONS. Despite achieving high LV pressures, precordial thumps were not effective in terminating VF, but did produce PVCs in asystole. Based on this data, a precordial thump cannot be recommended for VF, but its use in asystole should be further explored.
Abstract 220: Detection of Cysteine Sulfenic Acid Formation: Role in Reactive Oxygen Species-dependent VEGF signaling Linked to Endothelial Migration
Authors: Nakamura Yoshimasa , Kaplan Nihal , Poole Leslie B , Fukai Tohru , Ushio-Fukai Masuko 
Published: July 2021

NADPH oxidase Nox2-derived reactive oxygen species (ROS) have been implicated in VEGF receptor type2 (VEGFR2)-mediated signaling linked to endothelial cell (EC) migration. ROS-mediated protein modification involves oxidation of reactive cysteine residues to form a cysteine sulfenic acid (Cys-SOH) and subsequent oxidation products. However, the role of Cys-SOH formation in VEGF signaling and EC migration remains unknown. Using a newly-developed Cys-SOH trapping reagent, here we show that VEGF stimulation significantly increases the total Cys-SOH formation of proteins in HUVECs. VEGFR2 immunoprecipitates show significant increase in Cys-SOH within 5 min (90.3%), which remained elevated at least for 30 min (30.1%). This VEGF-induced Cys-SOH formation of VEGFR2 is prevented by pretreatment with a thiol donor antioxidant, N-acetylcysteine, which is associated with inhibition of VEGFR2 autophosphorylation (80.2%). The trapping of endogenous Cys-SOH by dimedone blocks VEGFR2 autophosphorylation (50.3%), its downstream phosphorylation of PLCgamma (70.4%) and ERK1/2 (90.1%) as well as EC migration (80.3%) without affecting p38MAPK phosphorylation. Wound scratch assay and immunofluorescence analysis reveal that Cys-SOH modified proteins are accumulated at the leading edge where they colocalize with Nox2, phospho-VEGFR2, F-actin and IQGAP1, a novel VEGFR2- and actin-binding scaffold protein, in actively migrating ECs. A significant increase in Cys-SOH is also seen in IQGAP1 coprecipitates (~250 kDa) following VEGF stimulation with peak at 2 min (50.1% increase). Knockdown of IQGAP1 using siRNA, or trapping of Cys-SOH block wound-induced Cys-SOH formation at the leading edge as well as EC migration toward the injured site. In summary, these results suggest that VEGFR2 and IQGAP1-associated proteins are targets for Cys-SOH formation at the leading edge in actively migrating ECs. The present study provides a novel mechanism of redox regulation in VEGF signaling linked to EC migration, and a rationale for the importance of identification of novel proteins that form Cys-SOH during repair process after injury and angiogenesis in vivo.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 354: Host Immune Factors and Donor Adult Stem Cells Mediate Myocardial Ischemia Repair
Authors: Tolar Jakub , Braunlin Elizabeth , McElmurry Ron T , Lees Christopher J , Riddle Megan , Mansoor Abdul M , Zhang Jianyi , Blazar Bruce R 
Published: July 2021

Cellular therapy with non-hematopoietic adult stem cells (ASC) has emerged as a novel strategy for treatment of myocardial infarction (MI). Cells from non-identical donors, however, are typically rejected by the immune system of recipient. To overcome this barrier to transplantation we induced MI by left coronary artery ligation followed by direct intramyocardial injection of ASC or saline in cohorts of syngeneic C57BL/6 (B6) immune competent versus B6 Rag/IL2Rγc (Rag/γc) T-, B- and natural killer-cell immune deficient mice. We made an unexpected observation that heart function was significantly improved in ASC-treated B6 mice, but not in ASC-treated Rag/γc mice; and that the beneficial effect of ASC was inversely correlated with ASC persistence (i.e., ACS were rejected by B6 mice but engrafted in Rag/γc mice). As the donor cells were rejected within several weeks by B6 animals we hypothesized that the host immune system and ASC provided trophic signals for cardiac repair early after injury. In search for anatomical correlation, we first assessed changes in capillary density. Four weeks after MI, significantly more capillaries (normalized to number of nuclei) were observed in the border zone of B6 animals treated with ASC versus saline (p = 0.01), and significantly fewer capillaries were found in the infarct zone when B6 animals (treated with ASC) were depleted of T-cells and NK-cells (p = 0.03). To gain mechanistic insight into the early events in the ASC-mediated repair, next we have assessed one week after MI ± ASC messenger RNA expression of genes known to be engaged in angiogenesis. In B6 mice the most prominent change in response to MI injury was 17-fold increased expression of tissue inhibitor of metalloproteinases 1. The ASC mediated response to MI injury was defined by increased expression of fibroblast growth factor 2, integrin αV, phophorylated form of vascular endothelial growth factor receptor 2 and endothelial-specific receptor tyrosine kinase (all p < 0.01). These data are the first to define the paracrine tissue repair factors necessary to produce therapeutic benefit in response to donor ASC after MI. Importantly, our data also suggest that MI is not solely a heart lesion, but rather a systemic inflammatory condition controlled by host immune system.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 1509: Inducible TBX3 Overexpression As A Tool For Biopacemaker Engineering
Authors: Boink Gerard J , Bakker Martijn L , Verkerk Arie O , Bakker Diane , de Bakker Jacques M , Seppen Jurgen , Christoffels Vincent M , Tan Hanno L 
Published: July 2021

Introduction: Currently constructed biopacemakers based on single gene transfer strategies function suboptimally, with periods of slow heart rates and instabilities during rest. In the sinoatrial node (SAN), the dominant native pacemaker, multiple genes are required for proper impulse formation and impulse propagation. TBX3 is an important regulator of the SAN gene program during heart development. We examined the effects of inducible TBX3 overexpression in adult hearts and in vitro we explored whether lentiviral TBX3 overexpression may be used in biopacemaker engineering.
Methods: In vivo atrial and ventricular expression levels of the connexin isoforms Cx43 and Cx40 (impulse propagation) and SCN5A were studied in mice with tamoxifen inducible overexpression of TBX3 using quantitative PCR analysis. Single neonatal rat cardiac myocytes were transduced with TBX3 expressing lentivirus to analyze the effects of TBX3 on action potentials and membrane currents (impulse formation) using the perforated patch-clamp technique.

Results: In vivo, Cx43, Cx40 and SCN5A, which are not or only moderately expressed in the native SAN, were severely down-regulated to 20%, 15%, and 40%, respectively, by TBX3 (n=12; p<0.01). Single neonatal cardiac myocytes overexpressing TBX3 exhibited faster spontaneous beating rates, along with decreased maximum diastolic potential, inward rectifier potassium current (I
K1
), and fast sodium current (I
Na
). These properties are typical of SAN pacemaker cells.

Conclusions: TBX3 can act as a strong repressor of the working myocardium gene program in the adult heart. Overexpression of TBX3 might be a useful tool in biopacemaker gene and cell therapy.
Abstract 1514: RXP-E: A Connexin43-Binding Peptide that Prevents Action Potential Propagation Block
Authors: Lewandowski Rebecca , Procida Kristina , Vaidyanathan Ravi , Jalife José , Nielsen Morten S , Taffet Steven M , Delmar Mario 
Published: July 2021

Gap junctions (GJ’s) provide a low resistance pathway for cardiac electrical propagation. The role of GJ regulation in arrhythmias is unclear, partly due to the limited availability of pharmacological tools. Recently, we showed that a peptide called “RXP-E” binds to the carboxyl terminal of connexin43 (Cx43) and prevents chemically-induced uncoupling in Cx43-expressing N2a cells. Here, we used pull-down experiments to show that RXP-E binds to adult cardiac Cx43. Patch-clamp studies revealed that RXP-E prevented heptanol-induced and acidification-induced uncoupling in pairs of neonatal rat ventricular myocytes (NRVM’s). Separately, RXP-E was concatenated to a cytoplasmic transduction peptide for translocation into the cytoplasm (construct CTP-RXP-E). The effect of RXP-E on action potential (AP) propagation was assessed by high resolution optical mapping in monolayers of NRVMs, containing approximately 20% of randomly distributed myofibroblasts. Conduction velocity (CV) was 164 ± 8mm/sec (avg±SEM; n=12; pacing frequency 2Hz) in untreated cells, and 158±10mm/sec, (n=6) and 180±7mm/sec (n=10) in monolayers treated with CTP-RXPE or a scrambled version of the peptide (CTP-Scr), respectively (pNS). Exposure of either untreated, or CTP-Scr-treated monolayers to heptanol caused propagation block. However, when heptanol (2 mmol/L) was added to the superfusate of monolayers loaded with CTP-RXP-E, AP propagation was maintained, albeit at a slower velocity (87±5mm/sec;n=4; P<0.001). Similarly, intracellular acidification (pHi=6.2) caused a loss of AP propagation in control or CTP-Scr monolayers; however, propagation was maintained in CTP-RXP-E treated cells, though at a slower rate (CV=93 ± 28mm/sec; n=4). Consistent with these results, patch clamp experiments revealed that RXP-E did not prevent heptanol-induced block of sodium or calcium currents, nor did it alter the voltage dependence or amplitude of Kir2.1/Kir2.3 currents. RXP-E is the first synthetic molecule known to:

bind cardiac Cx43;

prevent heptanol and acidification-induced uncoupling of cardiac GJ’s and

preserve AP propagation among cardiac myocytes.

RXP-E can be used to characterize the role of GJ’s in the function of multicellular systems, including the heart.
This research has received full or partial funding support from the American Heart Association, AHA Founders Affiliate (Connecticut, Maine, Massachusetts, New Hampshire, New Jersey, New York, Rhode Island, Vermont).
Abstract 1532: Rare Genetic Variant in the hH1 cDNA Clone, R1027Q, Dramatically Alters the Cellular Electrophysiological Phenotype Ascribed to the Common Polymorphism, H558R, and a Brugada Syndrome Mutation, R1512W: Implications for Functional Studies
Authors: Tan Bi-Hua , Ackerman Michael J , Makielski Jonathan C 
Published: July 2021

Background:
Previous studies in the
SCN5A-
encoded Na channel showed that amino acid substitutions at one position affected function of a Na channel containing a pathogenic mutation elsewhere. The first and most commonly used SCN5A cDNA clone (hH1) is the minor alternatively spliced transcript with an extra glutamine at position 1077 (Q1077), and also differs from the Na channel found in nearly all humans by virtue of a rare amino acid substitution (R1027Q). We hypothesized that R1027Q in previous studies using hH1 may have increased expression levels of the Brugada syndrome (BrS)-associated mutation (R1512W) and the common polymorphism (H558R).

Methods: We generated mutations in the alternatively-spliced
SCN5A
transcript containing Q1077 (as in the hH1 clone) as the wild type (WT) channel to generate channels with the following amino acid substitutions in addition to Q1077ins: H558R, H558R/R1027Q, R1512W, and R1027Q/R1512W. These channels were expressed in HEK-293 cells and current densities measured by whole cell voltage clamp.

Results: The current density for H558R was reduced dramatically (−7±2 pA/pF) whereas H558R/R1027Q exhibited normal current density (−297±56 pA/pF) comparable to WT (−310±52 pA/pF). The BrS mutation, R1512W-hH1, was characterized originally as having only subtle inactivation defects but normal current density. However, when we expressed R1512W in the patient’s true WT background (i.e. without R1027Q), the current density was attenuated significantly (−79±19 pA/pF) whereas the double mutant (R1027Q/R1512W) which replicated R1512W-hH1 showed nearly normal density (−180±21 pA/pF, −253±35 pA/pF for hH1, n=10–25 cells).
Conclusions: R1027Q, the rare genetic variant present in the hH1 cDNA clone, rescues expression of Na current for channels with H558R and the BrS1-associated mutation, R1512W. Using the hH1 clone which contains R1027Q as background (as is the case for nearly all previous studies of SCN5A mutations) may yield erroneous conclusions regarding the functional impact assigned to putative pathogenic mutations. It may be critical to study mutations in either true WT clones or in the patient’s own genetic background.
This research has received full or partial funding support from the American Heart Association, AHA Midwest Affiliate (Illinois, Indiana, Iowa, Kansas, Michigan, Minnesota, Missouri, Nebraska, North Dakota, South Dakota & Wisconsin).
Abstract 1632: Tie2-Deficient Mice Exhibit Increased Susceptibility to Endothelial Apoptosis, Arteriolar Muscularization, and Pulmonary Arterial Hypertension in Response to Interleukin-6
Authors: Kugathasan Lakshmi , Ray Julie Basu , Deng Yupu , Han Robin N , Dumont Daniel , Stewart Duncan 
Published: July 2021

Introduction: We have demonstrated downregulation in lung Tie2 receptor expression and activity in experimental models of PAH, implicating reduced Tie2 survival signaling in the pathogenesis of this disease. Therefore, we hypothesized that Tie2 deficiency would predispose to PAH due to increased endothelial cell (EC) apoptosis in response to environmental triggers.
Methods: Adult male Tie2± or littermate WT mice received saline or interleukin-6 (IL-6) at a rate of 200ng/kg/day via subcutaneous injections for 1 or 2 weeks.

Results: Significant elevation in RVSP (Fig.1

) was observed in IL-6 treated Tie2± mice (31 ± 3mmHg) compared to saline-treated Tie2 ± mice (25 ± 1mmHg) and IL-6 treated WT mice (22 ± 1mmHg). Following 1 week of IL-6 treatment, increased pulmonary microvascular EC apoptosis was observed by TUNEL in Tie2± mice compared to WT (6.3 ± 0.3% vs. 0.9 ± 0.1%, respectively; p < 0.01). Furthermore, after 2 weeks, a significant increase in pulmonary microvascular muscularization by SMA staining (Fig.2

) was seen in IL-6 treated Tie2±/mice compared to WT (36.4 ± 1.5% vs. 22.5 ± 1.1%, respectively; p < 0.01). Interestingly, Western blot analysis revealed a significant decrease in Angiopoietin-1 (Ang-1) level in the lung after 2 weeks of IL-6 treatment in Tie2± mice, and ELISA demonstrated a 60% decrease in Ang-1 secretion in vitro after incubation of pulmonary artery smooth muscle cells with IL-6 (p < 0.01).

Conclusions: Tie2± mice demonstrated enhanced susceptibility to pulmonary EC apoptosis, increased muscularization, and PAH following chronic exposure to IL-6, supporting an important protective role for endogenous Tie2 signaling in the lung microvasculature.

Figure 1.

Increased RVSP in Tie2
+/+
mice following 2 weeks of IL-6 treatment (*P < 0.05 compared to Saline Tie2
+/+
; † P < 0.01 compared to IL-6 WT)

Figure 2.

Increased pulmonary microvascular muscularization in Tie2
+/+
mice following 2 weeks of IL-6 treatment.
Abstract 3753: Critical Role of Scavenger Receptor-BI Expressing Bone Marrow-Derived Endothelial Progenitor Cells in the Attenuation of Allograft Vasculopathy by Human Apo A-I Transfer
Authors: Feng Yingmei , van Eck Miranda , Van Craeyveld Eline , Jacobs Frank , Van Linthout Sophie , Erdel Martin , Tjwa Marc , De Geest Bart 
Published: July 2021

Background: Accelerated endothelial regeneration mediated by enhanced endothelial progenitor cell (EPC) incorporation may attenuate the development of allograft vasculopathy.
Hypothesis: We investigated the hypothesis that modulation of EPC biology and attenuation of allograft vasculopathy by increased HDL cholesterol following human apo A-I (AdA-I) transfer requires scavenger receptor (SR)-BI expression in bone marrow-derived EPCs.
Methods: Bone marrow transplantations with SR-BI+/+ or SR-BI−/− bone marrow were performed 4 weeks before gene transfer or saline injection. E1E3E4-deleted vectors containing a hepatocyte-specific human apo A-I expression cassette or containing no expression cassette were injected via the tail vein. Two weeks later, a common carotid artery of a female Balb/c donor mouse was transplanted paratopically into male recipient C57BL/6 mice. To analyse EPC incorporation, sex mismatch bone marrow transplantations were performed in female C57BL/6 mice and incorporated EPCs were quantified by in situ hybridization for the murine Y-chromosome.
Results: Following AdA-I transfer, the number of circulating EPCs increased 2.0-fold (p<0.0001) at different time-points in C57BL/6 mice transplanted with SR-BI+/+ bone marrow but was unaltered in mice with SR-BI−/− bone marrow. The effect of HDL on EPC migration in vitro requires signaling via SR-BI and extracellular signal-regulated kinases (ERK) and is dependent on increased NO production in EPCs. Human apo A-I transfer 2 weeks before paratopic artery transplantation reduced intimal area at day 21 3.7-fold (p<0.001) in mice with SR-BI+/+ bone marrow but had no effect in mice with SR-BI−/− bone marrow. The number of CD31 positive endothelial cells lining the lumen and the number of incorporated EPCs was increased 3.0-fold (p<0.001) and 9.7-fold (p<0.001), respectively, in AdA-I treated chimeric SR-BI+/+ mice compared to control mice with SR-BI+/+ bone marrow. Endothelial regeneration and EPC incorporation was not increased after AdA-I transfer in chimeric SR-BI−/−mice.
Conclusion: Human apo A-I transfer-mediated endothelial regeneration to prevent allograft vasculopathy is strictly dependent on SR-BI expressing bone marrow-derived EPCs.