bluuebunny/crossref_metadata_2025_split huggingface dataset:
Abstract P157: Echogram Finding as a Marker of Resuscitation Outcome in Patients Who Were Treated with Extracorporeal-cpr after Out-of-hospital Cardiac Arrest Failed
Authors: watanabe kazuhiro , kikushima kimio , tominaga yoshiteru , tada katsushige , nishikawa kei , matsuzaki masakazu , tateda yutaka , ikeda harumi , yagi tsukasa , nagao ken 
Published: July 2021

BACKGRAUND) Since 1996, we performed E-CPR (PCPS, coronary reperfusion therapy and hypothermia) in patients who arrived at the ER in cardiac arrest and failed to respond to standard CPR. However, few studies of echogram were available for resuscitation outcome.
METHODS) A total of 24 patients treated with E-CPR were enrolled in this prospective study. Using echogram, cardiac function (CI, LVSVI, and aortic valve ejection time (AVET)) for cardiac resuscitation and common carotid artery (CCA) flow for cerebral resuscitation were investigated according to our E-CPR protocol.
RESULTS) Of the 32 patients, 17 (53%) were weaned from PCPS successfully, and 6 (18%) had a favorable neurological outcome at 30 days after out-of-hospital cardiac arrest. At the time of PCPS flow of 2.0 l/min, Succeeded PCPS weaning group was higher levels of AVET than failed PCPS weaning group (AVET 216.9 vs 135.5, p<0.0001). The favorable recovery group was a higher level of CCA flow than the unfavorable group (375.9 vs 168.0 p=0.0002). The CCA flow cut off value of 173ml/min for a favorable neurological outcome.
CONCLUSIONS) In patients who were treated with E-CPR, echogram findings at the time of PCPS flow of 2.0ml/min were a useful marker of resuscitation, especially CCA flow of 173ml/min or more was associated with improvement of a favorable neurological outcome.
Abstract P163: Accuracy to Diagnose Cardiac Arrest and Quickness to Start Chest Compression in Different BLS Algorithms; a Comparative Study
Authors: Tamura Tomoko , Tanigawa Koichi , Kusunoki Shinji , Sadamori Takuma , Otani Tadatsugu , Ishida Makoto , Ota Kohei , Yamaga Satoshi , Kida Yoshiko , Tsumura Ryu , Kondo Tomohiro , Takeda Taku , Iwasaki Yasumasa , Hirohashi Nobuyuki 
Published: July 2021

Background; BLS algorithms for health care providers or experience personnel recommended by AHA, European Resuscitation Council (ERC), and Japanese Resuscitation Council (JPN) differ with respect to the sequence of assessment and procedures. The differences may affect accuracy to diagnose cardiac arrest and quickness to start chest compression. We compared BLS algorithms recommended by these organizations with respect to accuracy of respiratory/circulatory assessment, and quickness to start chest compression using a computed manikin model.
Methods; Thirty three subjects (16 physicians and 17 medical students) were enrolled. The Sim-Man (Laerdal) was used to develop 2 scenarios (no pulse/no breathing, with pulse 60/min and breathing 10/min). The three algorithms and 2 scenarios were randomly assigned to the subject, and the accuracy to diagnose cardiac arrest and the time from confirmation of loss of consciousness to starting chest compression were evaluated.
Results; The rates of incorrect assessment of respiratory/circulatory status were AHA;9.8% (13 out of 132), ERC;9.1%(12 out of 132) and JPN;6.8%(9 out of 132)(n.s. among algorithms). When the results were analyzed with respect to clinical experiences of the subjects, i.e. physicians vs. medical students, significant differences were found between the groups: AHA;17.2% (11 out of 64), ERC;15.6% (10 out of 64), JPN;12.5% (8 out of 64) in students, whereas AHA;2.9% (2 out of 68), ERC;2.9% (2 out of 68), JPN;1.5% (1 out of 68) in physicians* (* p<0.05 vs. students). The time to starting chest compression were AHA;27.8±5.1 sec, ERC;18.6±3.2** sec, JPN;23.7±4.2 sec (**p<0.05 vs. AHA and JPN), and no significant differences were found between physicians and students.
Conclusions; No differences were found in accuracy of respiratory and circulatory assessment among the algorithms, although it may be influenced by clinical experiences of evaluators. The BLS algorithm starting CPR from chest compression such as ERC guidelines may reduce the time of no-flow status in cardiac arrest.
Abstract P176: Resumption of Cardiopulmonary Resuscitation after Defibrillation Induces Recurrence of Ventricular Fibrillation
Authors: Berdowski Jocelyn , van Zyll de Jong Liesbeth , Koster Rudolph W 
Published: July 2021

Introduction- Resuscitation guidelines 2005 advise to resume cardiopulmonary resuscitation (CPR) immediately after defibrillation. We hypothesized that this promotes recurrence of ventricular fibrillation (VF).
Methods- This was a prospective per-patient randomized controlled trial. We randomized Automated External Defibrillators (AEDs) used by first responders to either a) perform post-shock analysis and prompt rescuers to a pulse check - guidelines 2000 - or b) to resume CPR immediately after defibrillation - guidelines 2005. Between June 2006 and April 2008, we collected continuous ECG and impedance signal of all patients with a non-traumatic out-of-hospital cardiac arrest to whom a study AED was applied. We annotated and calculated time intervals between the first effective shock, moment of CPR resumption, moment of refibrillation, and subsequent defibrillation shock. Intervals are expressed as median and inter quartile range.

Results- We collected 120 ECGs of patients with a shockable rhythm: 61 were randomized to guidelines 2000 and 59 patients to guidelines 2005. In respectively 54% (33/61) and 56% (33/59) of the patients VF recurred after the first effective shock. Rescuers resumed CPR after 32 (24–45) and 8 (7–9) seconds (P<0.01), VF recurred at 35 (21–57) and 13 (8–25) seconds after the first effective shock (figure 1

; P=0.02), the time interval between resumption of CPR and refibrillation was 4 (−8–20) and 6 (1–22) seconds (P=0.59), and VF sustained for 98 (63–204) and 150 (98–261) seconds (P=0.15).

Conclusion- CPR induces recurrent VF. Immediate resumption of CPR after effective defibrillation is associated with early and longer lasting recurrence of VF.
Abstract 227: Activity of Soluble Guanylyl Cyclase, the Nitric Oxide Receptor, is Modulated by Cysteines Redox
Authors: Couloubaly Samba , Sayed Nazish , Hedhli Jamila , Baskaran Padmamalini , Beuve Annie 
Published: July 2021

The enzyme soluble guanylyl cyclase (sGC) increases cellular level of the second messenger cGMP upon stimulation by nitric oxide (NO), whose role is exemplified in the cardiovascular system where it governs smooth muscle cell proliferation, vascular relaxation and platelet aggregation. Various pathologies like diabetes, hypertension and hypercholesterolemia are associated with enhanced oxidative stress with increased formation of reactive oxygen (ROS) and nitrogen species (RNS). We recently showed that cysteines beta1C243 and beta1C122 are S-nitrosylated in sGC leading to its desensitization. We have now identified by Mass Spectrometry, two additional cysteines (beta1C571 and alpha1C516) as potentially modified. Our hypothesis is that loss in vascular reactivity in oxidative pathologies is mediated, in part, by desensitization of sGC via thiols oxidation. We studied the effect of oxidative stress on sGC in primary vascular smooth muscle cells (VSMC) by directly exposing them to hydrogen peroxide (H2O2) in the absence or presence of a catalase inhibitor Amino-Triazole (AT). H2O2 induced inhibition of NO-stimulated sGC activity in VSMC and in COS 7 cells transiently transfected with sGC. Desensitization of sGC was further increased in VSMC treated with both H2O2 and AT. Next, we conducted mutational analysis of the 4 cysteines to assess their involvement in redox sensing. Replacement of C571 and C122 eliminated the oxidative-dependent desensitization observed in the wild-type. In addition, peroxynitrite, a strong oxidant, inhibited the NO-stimulated sGC activity in a purified system without oxidation of the heme. In conclusion, our results suggest that sGC activity is directly modulated by the redox state of the cells. Moreover, the identified 4 cysteines can be modified by both ROS and RNS suggesting a complex modulation. Ultimately, our goal is to determine whether loss of vascular reactivity in oxidative pathophysiologies is in part mediated by desensitization of sGC and what are the involved cysteines.
This work was supported by NIH GM067640, HL089771.
Abstract 308: Rgs2 Is An Endogenous Inhibitor Of Insulin Signaling
Authors: Sharma Prem , Bever Jennie , Heximer Scott , Dessauer Carmen , Olefsky Jerrold M 
Published: July 2021

Background: Insulin resistance is the hallmark of type 2 diabetes and is a known risk factor for the development of cardiovascular diseases. We have determined that overexpression of a GTPase-activating protein, RGS2 decreases insulin sensitivity. This study describes RGS2 regulation of insulin signaling pathways in order to assess whether this information can be used to reverse insulin insensitivity in diabetes.
Hypothesis, Methods and Results: RGS2 protein levels were elevated 3 to 5-fold in white adipose tissues from ob/ob and high fat diet induced Insulin Resistant mice. Further, RGS2 protein is elevated in insulin resistant 3T3-L1 adipocytes treated chronically with either insulin, ET-1, or TNF-aplha. Further, SiRNA knockdown of endogenous RGS2 protein increases basal, insulin independent and insulin-dependent GLUT4 translocation. We hypothesized that the RGS2 regulatory system is defective/overactive in insulin resistance, and that a modulation of this regulatory system by RGS2 inhibition would improve insulin sensitivity. Thus, we determined the mechanisms whereby RGS2 modulates insulin sensitivity in 3T3-L1 adipocytes; focusing on insulin-regulated G-protein/PI3-K pathways leading to GLUT4 translocation and glucose uptake; utilizing adenoviruses over-expressing wild-type and mutants RGS2, as well as by siRNA-mediated knock down of endogenous RGS2. We overexpressed the Wild-Type (WT), GTPase defective (GD), and plasma membrane translocation defective (TD) RGS2 proteins in 3T3-L1 adipocytes. Overexpression of WT RGS2 leads to ~ 50% inhibition of insulin induced 2-DOG uptake, without affecting IR Tyr phosphorylation. RGS2 constitutively associates with Galpha/q11, and prevent its Tyr phosphorylation and activation by insulin. Interestingly, insulin-stimulated PKClambda phosphorylation was completely blocked by RGS2, whereas, AKT phosphorylation was minimally inhibited. Neither the insulin receptor tyrosine phosphorylation nor insulin-stimulated MAPK phosphorylation was affected by RGS2.
Conclusion: This study identifies a novel role of RGS2 in cellular insulin resistance by negatively regulating signaling through the Galpha/q11 pathway to glucose uptake.
This research has received full or partial funding support from the American Heart Association, AHA Western States Affiliate (California, Nevada & Utah).
Abstract 350: Toll-like Receptor 2 Activation, Especially In Circulating Leukocytes, Mediates Myocardial Ischemia/Reperfusion Injury In Mice
Authors: Arslan Fatih , Pasterkamp Gerard , Timmers Leo , van Middelaar Ben , Doevendans Pieter A , de Kleijn Dominique P 
Published: July 2021

OBJECTIVES. Myocardial ischemia/reperfusion (MI/R) injury is characterized by an inflammatory response through NF-κB, increase of infarct size and worsening of cardiac function. Toll-like receptors (TLRs) are part of innate immunity and initiate the same inflammatory reaction. Here we studied in vivo to what extent TLR2 is involved in myocardial damage and what the relative contribution is of TLR2 expression in parenchymal cells and leukocytes to myocardial damage during MI/R in mice.
METHODS. C57Bl6J mice underwent 30 minutes ischemia - 24 hours of reperfusion. Four experimental groups were studied: TLR2 knock-out (TLR2 KO) mice (n=10), saline treated wild-type (WT) mice (n=10), generated chimeric WT mice with TLR2 KO bone marrow (BLOOD KO; n=7) and chimeric TLR2 KO mice with WT hematopoietic cells (ORGAN KO; n=7). Saline was administered via the tail vein 5 minutes prior to reperfusion. After 24 hours, the LCA was ligated again at the level marked by the suture left in place. Mice were terminated and infarct size (IS) was measured as a percentage of the area at risk (AAR) using 4% Evans’ blue dye injection in the aortic root and triphenyltetrazolium chloride (TTC) staining (fig. 1). Data are presented as Mean±SEM.
RESULTS. The AAR as percentage of the left ventricle was similar between groups: TLR2 KO 41%, saline 41%, Blood KO 41%, Organ KO 42%. Saline treatment resulted in 34.5%±3.3 of infarction, whereas in TLR2 KO mice infarct size decreased to 23.0%±2.9 (p=0.029 vs. saline). Infarct size in BLOOD KO mice was 22.9%±2.7 (p=0.024 vs. saline), while ORGAN KO mice had 33.9%±3.2 (p=0.998 vs. saline) of infarction within the area at risk (fig. 2).
CONCLUSION. TLR2 deficiency significantly reduces infarct size with ~33% compared to saline treatment in mice after 30 minutes of ischemia and 24 hours of reperfusion. We show for the first time that TLR2 expression in circulating leukocytes plays an important role in infarction after MI/R injury. Systemic inhibition of TLR2 may be a potential therapeutic target in the treatment of patients with acute myocardial infarction.
Abstract 382: The Bone Morphogenetic Protein Pathway Mediates the Effects of H11 Kinase/Hsp22 on Cardiac Cell Growth and Survival
Authors: Sui Xiangzhen , Li Dan , Hedhli Nadia , Qiu Hongyu , Gaussin Vinciane , Depre Christophe 
Published: July 2021

The bone morphogenetic protein (BMP) pathway is a major signaling mechanism during cardiac development but it has no clear function in the post-natal heart. Here, we tested the hypothesis that BMP mediates the physiological effect of the cardiac chaperone H11Kinase/Hsp22 (H11K).
Expression of H11K increases during both cardiac ischemia and overload, and its cardiac-specific over-expression in a transgenic (TG) mouse is sufficient to provide major protection against ischemia and to promote cardiac cell growth, which involves the activation of phosphatidylinositol-3-kinase (PI3K) and of its effector Akt. We tested whether H11K-induced activation of PI3K is mediated by BMP. Microarray comparison between hearts from TG and wild type (WT) mice showed an up-regulation of the BMP receptor subunits Alk3 and BMPR-II, as well as of the BMP receptor ligand BMP4, which was confirmed at the protein level (P<0.01 vs WT). Activation of the BMP pathway in TG mice was confirmed by increased phosphorylation of the canonical BMP effectors Smad 1/5/8 (P<0.01 vs WT). The mechanism was further studied in isolated cardiac myocytes. Adeno-mediated over-expression of H11K was accompanied by significant 2–3-fold increase in PI3K activity, phospho-Akt, Smad 1/5/8 phosphorylation and cell growth as measured by [3H]phenylalanine incorporation, and by a 70% reduction in H2O2-mediated apoptosis (all values, P<0.01 vs control). All these changes mediated by H11K in myocytes were abolished upon addition of the BMP antagonist noggin. In pull-down experiments, H11K co-precipitated with both Alk3 and BMPR-II, and increased the association of these two subunits into a functional receptor. Accordingly, Smad 1/5/8 phosphorylation in presence of BMP4 was enhanced by 5-fold upon H11K over-expression, whereas it was decreased by 3-fold upon H11K knockdown (both, P<0.01 vs control), which shows that H11K potentiates the BMP receptor signaling pathway. Therefore, potentiation of the BMP receptor pathway by H11K promotes the activation of the PI3K/Akt pathway and dictates the physiological effects of H11K on cardiac cell growth and survival, which shows a novel role for BMP signaling in post-natal heart.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 1683: Ca2+/Redox-Sensitive Tyrosine Kinase PYK2 Promotes Atherogenesis through OxLDL/ROS/p21-Dependent Premature Senescence and Cytokine Induction in Endothelium
Authors: Katsume Asako , Okigaki Mitsuhiko , Matsui Akihiro , Yamaguchi Shinichiro , Kishita Eigo , Yamada Hiroyuki , Matsubara Hiroaki 
Published: July 2021

Background: Calcium/redox-sensitive tyrosine kinase PYK2 plays crucial roles in cell migration. Analysis of PYK2-deficient macrophages has been reported that their directional migration was impaired due to dysfunction of PI3K, small GTPase Rho, and Ca (2+)-mobilization. Since monocyte/macrophage plays crucial role in atherogenesis, we newly generated the PYK2-knock-out mice and investigated the role of PYK2 in atherogenesis.
Methods: PYK2−/− mice (P-KO) were crossbred with ApoE−/− mice (E-KO), and PYK2−/−/ApoE−/− double knockout (D-KO) mice were established. Four-week-old mice were fed with high-fat-diet for 8 weeks, and the thoracic aorta and aortic root were histologically analyzed. Then we studied the mechanisms of the difference in atherogenesis.
Results: At the 8th week, atherosclerotic area of thoracic aorta in D-KO was less than E-KO (~54%, P < 0.01, n = 15, respectively). Numbers of infiltrating macrophage in D-KO mice was also reduced (~52%, P < 0.01, n = 15). We also verified that no significant difference in atherosclerotic area between E-KO recipient with D-KO bone marrow and D-KO recipient with E-KO bone marrow. At the 7th day, the expression of VCAM1, and MCP-1 in the thoracic aorta in D-KO mice was inhibited (~43 to 58%, n = 5, P < 0.01, respectively). Inflammatory cells were barely detected in the region at that time. TNF-alpha and MCP-1 mRNA of peripheral blood-leukocytes in D-KO was also 38% lower (P < 0.05, n = 5 each). In the primary-cultured P-KO endothelial cells, TNF-alpha-induced expressions of VCAM-1 and MCP-1 was decreased to 31 and 32% respectively, compared to the wild-type (WT) (each n = 5, P < 0.01). Lysophosphatidylcholine (LPC), the component of Oxidized LDL, -induced Reactive Oxygen Species (ROS)-production was attenuated to 54% of the WT (p < 0.05) using DCF staining, and the high cholesterol diet induced ROS-production in endothelium in D-KO were decreased by 8-OHDG staining. Senescence-associated-beta-gal-stained area and ROS-dependent expression of p21 in the thoracic aorta in D-KO-mice was diminished. In P-KO ECs, LPC-induced p21 expression via Ets-1 or STAT1 was also decreased markedly.
Conclusion: PYK2 promotes atherogenesis by inducing ROS/p21-dependent premature senescence and cytokine induction in endothelium.
Abstract 1709: Transforming Growth Factor Beta Inhibition Increases Matrix Metalloproteinase-9 Activity and Enhances Elastin Degradation in a Murine Model of Kawasaki Disease
Authors: Alvira Cristina M , Kim Yu-Mee , Guignabert Christophe , Wang LingLi , Rabinovitch Marlene 
Published: July 2021

Background: Kawasaki disease (KD) is a leading cause of acquired heart disease in children. However, the molecular mechanisms leading to coronary aneurysms, and the host factors determining high-risk patients are unknown. We have previously shown that mice haploinsufficient for tropoelastin (EL ±), develop more severe destruction of the coronary elastin compared to wild type (WT) mice after injection with Lactobacillus casei wall extract (LCWE), an inducer of coronary arteritis. In contrast to the beneficial effect of TGFβ blockade on the aneurysms that form in Marfan syndrome (MS), we hypothesized that TGFβ protects against aneurysm formation in this inflammatory model by:

enhancing tropoelastin; and

suppressing proteolytic activity.

Methods: WT and EL ± mice were given either TGFβ neutralizing antibody (TGFβ-Nab) or control IgG in addition to LCWE. At 14d, tropoelastin and plasminogen activator inhibitor-1 (PAI-1) protein was determined, and matrix metalloproteinase (MMP)-2 and -9 and serine elastase activity was measured. Elastin degradation and total medial elastin content was assessed by morphometric analysis at 42d.
Results: TGFβ blockade worsened the LCWE-mediated fragmentation of the coronary elastin, with areas of complete dissolution of the external lamina in WT mice, and even more severe features in EL ± mice. Tropoelastin protein was 40% lower in the EL ± vs. WT mice after LCWE (P < 0.05), and TGFβ blockade further exaggerated this discrepancy. TGFβ-Nab markedly reduced PAI-1 in the WT mice after LCWE (P < 0.05), and produced a similar pattern in the EL ± mice, and induced a four-fold induction of MMP-9 activity in both genotypes. This effect was associated with increased elastin fragmentation (P < 0.05), and decreased total medial elastin content (P < 0.05), despite inhibition of the LCWE-mediated induction of serine elastase activity.
Conclusions: We conclude that:

diminished tropoelastin expression worsens elastin destruction in the setting of acute coronary arteritis; and

TGFβ protects the vasculature in this model by maintaining PAI-1 levels and suppressing activation of MMP-9.

Thus strategies to block TGFβ, currently in use to prevent aneurysms in MS, are unlikely to be beneficial in KD, and may be detrimental.
This research has received full or partial funding support from the American Heart Association, AHA National Center.
Abstract 3379: cGMP Specific Phosphodiesterase Type 5A Activity is Regulated by S-nitrosylation at Cys 181
Authors: Murray Christopher I , Gebska Milena A , Haile Azeb , Zhang Manling , Kass David A , Champion Hunter C , Van Eyk Jennifer E 
Published: July 2021

Introduction: cGMP specific phosphodiesterase type 5A (PDE5A) has a key role in limiting the effect of the second messenger cGMP as demonstrated by the use of the specific inhibitor, sildenafil. However, the mechanism by which PDE5 activity is regulated is not fully understood. Recently, it has been reported that PDE5A specifically degrades the pool of cGMP produced by the nitric oxide (NO) stimulated soluble guanylate cyclase. NO is known to regulate other proteins in this pathway through S-nitrosylation, a redox modification where an NO group is covalently added to the sulfur atom of a cysteine. Here we test the hypothesis that PDE5 activity is regulated by S-nitrosylation and determine the critical modified cysteine residues.
Methods: Rates of cGMP hydrolysis were measured by an in vitro activity assay using purified mouse flag-PDE5 treated with the NO-donor, S-Nitrosoglutathione (GSNO, 1–100μM) or control. The S-nitrosylation status of PDE5A was determined by biotin switch assay of cell lysates over expressing flag-PDE5A using the equivalent conditions. After NO modifications were replaced with biotin moieties, labeled proteins or trypsin digested peptides were captured with streptavidin agarose and evaluated by western blot or tandem mass spectrometry, respectively.
Results: PDE5A activity was found to be decreased in a dose dependent manner with NO donor inducing a 25.0 ± 3.8% (n=4, p<0.01) decrease with 100μM GSNO treatment compared to controls. PDE5A was S-nitrosylated by the NO donors in a similar dose dependent manner when analyzed using the biotin switch assay. Subsequent mapping studies identified 2 potential sites of S-nitrosylation at C181 and C210, both of which are located in the N-terminal regulatory domain. Independent mutation of candidate cysteines to serine residues revealed that C181 is more receptive to NO modification than C210. Additionally, the C181S PDE5A was found to be resistant to the NO-donor dependent decrease (0.55 ± 2.3%, p=0.9) in activity while C210S activity was found to be depressed in the presence of 100μM GSNO (28.9 ± 1.7%, p<0.01) (n=4).
Conclusions: These data indicates that PDE5A activity is negatively regulated by S-nitrosylaion at C181 which may contribute to the overall regulation of cGMP signaling in the cell.
This research has received full or partial funding support from the American Heart Association, AHA Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).