tbuckley/cabot-search huggingface dataset:
Abstract 17780: Efficacy of Bag-Mask Ventilation for Ventricular Fibrillation Sudden Cardiac Arrest
Authors: Yoshio Tahara, Naoto Morimura, Kazuo Kimura, Yasufumi Oi, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao
Journal: Circulation (2011)

Background: If bag-mask ventilation is adequate, an advanced airway is not urgently required. Although rescuers may defer insertion of an advanced airway until the patient fails to respond to initial cardiopulmonary resuscitation (CPR) and defibrillation attempts or has return of spontaneous circulation (ROSC), its effects and optimal timing remain unclear. Methods: An observational study was performed in 547,218 patients who had out-of-hospital cardiac arrest (OHCA) in Japan and received CPR between January 1, 2005 and December 31, 2009. Of these patients, 15,675 in whom age was from 18 to 74 years, OHCA was cardiogenic, the scene of OHCA was witnessed, bystander CPR was performed, and initial rhythm was ventricular fibrillation (VF) were studied. The subjects were divided into two groups according to the method used for airway management by emergency medical service (EMS) personnel: 8,101 who used a bag-valve mask (bag-mask ventilation group: BMV group) and 7,574 who used an advanced airway including a supraglottic airway device and endotracheal tube (advanced airway group: AA group). The rates of ROSC from the initiation of EMS CPR to arrival at the hospital were compared. Next, subjects who did not have ROSC within 45 minutes before arrival at the hospital were divided into two groups, the pre-hospital non-ROSC BMV group (N=5,127) and the pre-hospital non-ROSC AA group (N=5,867), and neurologic outcomes at 30 days were compared. A favorable outcome was defined as a Cerebral Performance Category (CPC) of 1 or 2. Results: The rate of ROSC from the initiation of EMS CPR to arrival at the hospital was higher (35.5% vs. 19.8%, p&lt;0.01) in the BMV group than in the AA group. The rate of favorable outcomes was higher (5.7% vs. 2.9%, p&lt;0.01) in the pre-hospital non-ROSC BMV group than in the pre-hospital non-ROSC AA group. In particular, the rate of favorable outcomes was higher in the pre-hospital non-ROSC BMV group than in the pre-hospital non-ROSC AA group during the first 25 minutes after the initiation of EMS CPR. Conclusions: In patients with ventricular fibrillation sudden cardiac arrest, the use of a bag-valve mask for airway management increases the rates of ROSC and favorable outcomes, particularly during the initial period from EMS CPR to arrival at the hospital.
Abstract 35: Clinical Characteristics and Outcomes of Out-of-Hospital Cardiac Arrest Patients in Areas of Tremendous Snowfall
Authors: Mamoru Hase, Hiroshi Akasaka, Hiroyuki Hanada, Nobuaki Kokubu, Junichi Nishida, Kazufumi Tsuchihashi, Tetsuji Miura, Naohiro Yonemoto, Hiroshi Nonogi, Takeshi Kimura, Ken Nagao
Journal: Circulation (2011)

Backgrounds: The snow removal is a hard work in the tremendous snowfall area. Because it is difficult to limit to light work in consideration for the physical condition, the heart attacks are often experienced during the snow removal. Little information is available with regard to the severe heart attacks such as out-of-hospital cardiac arrest (OHCA) during the snow removal. The purpose of this study was to evaluate the characteristics and clinical outcomes of OHCA patients in the tremendous snowfall area. Methods: A prospective, nationwide, population-based registry of out-of-hospital cardiac arrests has been conducted by the Fire and Disaster Management Agency of Japan between January 2005 and December 2009. We enrolled all OHCA patients of presumed cardiac etiology. The tremendous snowfall area was defined as the prefectures including the city which five-year average annual cumulative snowfall depth was over 50 cm. We compared the clinical characteristics and the neurological outcomes between the tremendous snowfall area (group S) and the other area (group N). Results: During the five years, 297,111 patients had OHCA of presumed cardiac etiology. Though the time interval from emergency call to arrival of emergency life-saving technician in group S was longer (7.36 min) than that in group N (7.12 min), the time intervals from emergency call to restoration of spontaneous circulation in group S (19.87 min) and group N (19.72 min) were the same. The one-month survival rate in group S (5.06%) was lower than group N (5.28 %). The favorable neurological recovery rates in group S (2.67 %) and group N (2.77 %) were the same. Comparing the monthly outcomes, the one-month survival rate in group S (6.03 %) was lower than that in group N (7.02 %) in June. Though the large number of OHCA was occurred, there were no significant differences in the one-month survival and favorable neurological recovery rates between two groups in winter. Conclusion: This study suggested that tremendous snowfall didn’t affect the outcomes of OHCA patients much.
Abstract 9201: Transplantation of Adipose Tissue-Derived Multi-Lineage Progenitor Cells Reduces Serum Cholesterol in Hyperlipidemic Watanabe Rabbits
Authors: Hanayuki Okura, Ayami Saga, Mayumi Soeda, Jyunko Tani, Mariko Moriyama, Hiroyuki Moriyama, Sihizuya Yamashita, Akihiro Ichinose, Shinya Tahara, Takao Hayakawa, Akifumi Matsuyama
Journal: Circulation (2011)

Background : Familial hypercholesterolemia (FH) is an autosomal co-dominant disease characterized by high concentrations of pro-atherogenic lipoproteins and premature atherosclerosis. We examined the response to in situ stem cell therapy using adipose tissue-derived multi-lineage progenitor stem cells (hADMPC) in the LDL-receptor deficient Watanabe heritable hyperlipidemic (WHHL) rabbit, an animal model for homozygous FH. Methods : WHHL rabbits received either normal control rabbit-derived, GFP-rabbit-derived or WHHL rabbit-derived ADMPC (normal-ADMPC, GFP-ADMPC and diseased-ADMPC, respectively) via the portal vein. This was followed by 12-week immunosuppressive therapy to avoid allogenic rejection. In situ survival and differentiation of the ADMPC into hepatocytes was examined by flow cytometry and immunohistochemical analysis, respectively. Lipid profile was examined before-, and 4-, 8- and 12 weeks after transplantation. LDL clearance was examined at the end of the study by125I-LDL turnover. Results : In situ survival of GFP-ADMPC was confirmed after transplantation. The cells integrated into the hepatic parenchyma and co-expressed GFP and hepatocyte markers such as albumin, indicating that the cells were reprogrammed into hepatocytes-like cells in situ . Transplantation of normal-ADMPC but not diseased-ADMPC resulted in a significant reduction of serum total- and LDL- cholesterol after transplantation. 125I-LDL turnover study showed significant improvement in the rate of LDL clearance in the WHHL rabbits with transplanted normal-ADMPC but not in those transplanted with diseased-ADMPC. Conclusion : Transplantation of ADMPC but not diseased ones corrected the metabolic defects in WHHL rabbits, suggesting that ADMPC transplantation is a potentially useful therapy for FH.
Abstract 18237: Inhibition of Adenylyl Cyclase Type 5 Protects Against Obesity and Diabetes
Authors: David Ho, Lin Yan, Xin Zhao, Shumin Gao, Kousaku Iwatsubo, Yoshihiro Ishikawa, Dorothy E Vatner, Stephen F Vatner
Journal: Circulation (2011)

Adenylyl cyclase type 5 (AC5) is one of 9 major isoforms of AC. Mice with AC5 gene disruption (knockout, KO) live one third longer than wild type (WT) littermates. Like caloric restriction, the most commonly studied model of longevity, the AC5KO mice weigh 12% less than WT (p&lt;0.05) and have less body fat, i.e., adiposity index, calculated by dividing the sum weights of the three major fat pads (inguinal, retroperitoneal, gonadal) by the body weight, was 50% lower than WT (p&lt;0.05). The first goal of this study was to determine if AC5KO mice are protected, not only against obesity, but also diabetes. Insulin sensitivity, assessed by blood glucose measurement following insulin injection, was improved by 24% compared to WT. Glucose tolerance was also improved, p&lt;0.05. A major limitation of studies in genetically altered mouse models, is that it is difficult to translate these results to the bedside, since it is not possible to knock out a gene in patients. Accordingly, we identified a pharmacological inhibitor of AC5, vidaribine, and examined the extent to which it ameliorated obesity and diabetes. First we demonstrated its selectivity for AC5; the inhibitor reduced inotropic responses to isoproterenol more than WT only in AC5 cardiac transgenic mice, but not in AC6 cardiac transgenic mice. To induce obesity, WT mice were fed a high fat diet feeding for 2 months, increasing body weight by 51% over mice fed a standard diet. WT mice with high fat diet and AC5 inhibitor on board for an additional 3 months, compared with WT mice on vehicle and high fat diet, increased body weight and adiposity index less, p&lt;0.05, by 20% and 28%, respectively, while insulin resistance was reduced by 76% and glucose tolerance was improved by 66% (p&lt;0.05). In AC5KO mice on the high fat diet insulin resistance was also reduced and glucose tolerance was also improved compared to WT on the high fat diet, similar to that observed with the AC5 inhibitor on the high fat diet. Thus, inhibition of AC5 provides a novel target for obesity and diabetes; the effective pharmacological inhibitor of AC5 enhances its clinical relevance.
Abstract 19639: Long-Term Change in Cardiovascular Risk Factor Profile at Baseline and 39-Year Follow-Up and Hs-C-Reactive Protein - - The Chicago Healthy Aging Study (CHAS)
Authors: Thanh Huyen T Vu, Amber Pirzada, Norrina B Allen, Daniel B Garside, Martha L Daviglus
Journal: Circulation (2012)

Background: High high-sensitivity C-reactive protein (hs-CRP) levels are associated with adverse levels of individual cardiovascular disease (CVD) risk factors and incident CVD events. However, little is known on the association of long-term changes in RF profile -- from young adulthood to older age -- with hs-CRP levels at older age. Methods: Using data from CHAS, we assessed association of changes in CVD RF status from baseline (1967-73) to follow-up (2007-10) with follow-up hs-CRP levels (see Table for definition of RF groups). Hs-CRP was dichotomized as &gt;3 mg/l (cutpoint for high risk of developing CVD). Participants with hs-CRP &gt;10 mg/l were excluded. Results: The study sample consists of 1,321 participants -- 27% women, 9% African American, baseline ages 25-44 years, free of major ECG abnormalities and MI (at baseline), mean follow-up age 71. After 39 years of follow-up, 17% of persons (117/681) with no adverse RFs at baseline remained RF-free at follow-up and 1.6% of persons with any 1+ RFs at baseline became RF-free at follow-up (62/640) (Group A). With adjustment for baseline age, sex, race, education, and current aspirin use, prevalence of high hs-CRP (&gt;3mg/l) was lowest in Group A (11%) and higher in Group E (≥1 RF at both exams and not taking cholesterol-lowering medication) (34%) and in Group C (0 baseline RF status but ≥1 RF at follow-up) (26%). Further, within each risk category, persons who took cholesterol-lowering medication had a lower likelihood of high Hs-CRP than their counterparts not taking it (see Table). Conclusion: Long-term absence of RFs or, among those with baseline adverse risk factors, improvement in risk status to having no adverse RFs in older age is associated with lower prevalence of high CRP levels. RF burden in both young adulthood and older age were associated with substantially increased odds of having high hs-CRP levels at older ages, especially for those who did not take cholesterol-lowering medication.
Abstract 18304: Identification of MicroRNAs Dysregulated in a Porcine Model of Coronary In-stent Restenosis
Authors: Keith E Robertson, Robert A McDonald, Keith G Oldroyd, Simon Kennedy, Andrew H Baker
Journal: Circulation (2012)

Introduction Vascular injury following stent delivery results in proliferation and migration of smooth muscle cells (SMC) leading to in-stent restenosis. MicroRNAs (miRs) are short, non-coding ribonucleic acids that act to control gene expression at a posttranscriptional level. MiR-21 and -221 positively regulate SMC proliferation through modulation of cell-cycle regulators. MiR-143 and -145 are important in the maintenance of vascular SMC in the differentiated state. Hypothesis We hypothesised that expression patterns of these key regulatory miRs in the vasculature would alter in response to stent-induced injury. Methods Pigs received standardized bare-metal (cobalt alloy) or drug-eluting (zotarolimus) stents (n=4/group), over-expanded to induce vessel injury, and were euthanized at 0, 7 or 28 days (BMS) and 28 days (DES). Total RNA was extracted from stented tissue. MiR expression levels were determined by quantitative real-time polymerase chain reaction and normalized to miR-199a-3p, a suitable endogenous control with mean cycle threshold + SD 25.70 + 0.84 across all samples. All comparisons made against control vessels (unstented arteries). Results MiR-21 levels were upregulated at 7 and 28 days in both stent types. No differences were seen between BMS and DES at 28 days. MiR-221 levels were elevated at Day 7 in the BMS group, returning to baseline at 28 days. MiR-145 levels showed immediate downregulation (Day 0) and stayed significantly low in all groups. MiR-143 levels did not show this immediate change, but were otherwise similar to miR-145. Levels of miR-145 only were significantly lower in arteries receiving DES compared with BMS at 28 days (75% vs. 48% downregulation). Conclusions In conclusion, vascular miRs show altered expression following stent insertion. MiR-145 levels were lower in arteries with DES, in comparison to BMS, at 28 days. This provides potentially important information for future manipulation of miRs in the vessel wall.
Abstract 18312: Cumulative Radiation Exposure in Pediatric Patients with Congenital Heart Disease
Authors: Mark Walsh, Michelle L Noga, Jennifer M Rutledge
Journal: Circulation (2012)

Introduction: The purpose of our study is to look at cumulative radiation exposure in a contemporary cohort of patients with congenital heart disease undergoing single ventricle palliation. Methods: This is a single center, retrospective study of pediatric patients undergoing Fontan completion between May 2005 and May 2010. Radiation exposure from all procedures including cardiac catheterizations, CT scans, plain film radiography, and nuclear medicine scans were evaluated. Radiation dose was calculated as the dose area product (μ Gy.m 2 ) and was measured in all cardiac catheterizations and CT scans. Radiation exposure from chest radiography was estimated based on age at the time of exposure. Patients that died prior to reaching Fontan completion or who underwent cardiac transplantation were excluded from the study. Results: Ninety-nine patients who underwent Fontan completion at a mean age of 3.6±1.5 years (range 1.4 - 8 years) were included in the study. There were 41 females and 58 males. Fifty-four patients had a diagnosis of hypoplastic left heart syndrome and 68 of the total cohort had a dominant morphologic right ventricle. Mean number of chest x-rays was 32±8 (range 10 - 285) with a mean cumulative total exposure of 1,536 μ Gy.m 2 per patient. Mean number of cardiac catheterizations was 3.6±1.3 (range 1-8), mean fluoroscopy and cine angiography exposures per case were 1103±245 and 1412±273 μ Gy.m 2 giving a mean cumulative exposure of 9,054 μ Gy.m 2 per patient for all catheterizations. Mean number of CT scans performed was 0.44±0.4 (0-11); the mean exposure was 352 μ Gy.m 2 giving a mean cumulative total of 154 μ Gy.m 2 per person. A total of 5 lung perfusion scans were carried out. The mean cumulative total exposure for all procedures was 10,744 μ Gy.m 2 . Conclusion: Radiation exposure in patients with congenital heart disease undergoing single ventricle palliation is quite variable. Cardiac catheterization and chest radiography account for most of the radiation exposure. The level of exposure is below threshold levels however given the age of these patients this should be interpreted with caution. Consideration should be given to the introduction of patient radiation monitoring, notification and surveillance for long-term side effects from exposure.
Abstract 18309: Familial Atrial Fibrillation - Common Atrial Fibrillation Susceptibility Alleles and Response to Catheter Ablation
Authors: Andreas Bollmann, Laura Ueberham, Helge Immo Lehmann, Gerhard Hindricks, Arash Arya, Volker Adams, Daniela Husser
Journal: Circulation (2012)

Background: Familial atrial fibrillation (AF) is common but AF-causing rare genetic variants are infrequently found supporting the multigenetic nature of this arrhythmia. On the other hand, genome-wide association studies have identified common AF susceptibility alleles, but their possible relation with familial AF is unknown. The aim of this study was to compare familial and sporadic AF with respect to common alleles on chromosomes 1q21 (rs13376333), 4q25 (rs10033464 and rs2200733) and 16q22 (rs7193343) and rhythm outcome after radiofrequency catheter ablation (CA). Methods: A total of 393 patients (mean age 59 +/- 10 years, 68 % males, 38 % persistent AF), who underwent CA were studied. The family history of AF was considered positive if at least one of the first-degree family members had AF based on patient's interviews, chart and ECG reviews. Genotypes were determined using real-time polymerase chain reaction and fluorescence resonance energy transfer. AF recurrence &gt; 30 sec was detected using serial 7-day Holter ECG recordings after a blanking period between 3 and 12 months after radiofrequency CA. Results: Familial AF was found in 14.2 % and was associated with the absence of structural heart disease (OR 1.888, 95 % CI 1.017 - 3.505, p=0.042) and age (OR 0.964, 95 % CI 0.938 - 0.991, p=0.009). In familial AF, minor allele frequency of AF risk alleles on chromosomes 1q21 (40.0 % vs. 32.8 %) and 4q25 (rs10033464: 26.4 % vs. 11.0 % and rs2200733: 39.4 % vs. 27.2 %) tended to be higher compared with non-familial AF. Using a dominant genetic model, rs2200733 on chromosome 4q25 showed the strongest association with familial AF (OR 2.222, 95 % CI 1.015 - 4.865, p=0.042). AF recurrence was observed in 27.6 % of non-familial AF and in 30.9 % of familial AF patients (p=0.621). Conclusion: This study, for the first time, shows a dominant modulating function of a common AF susceptibility allele on chromosome 4q25 also in familial AF. Ablation outcome is comparable in familial and non-familial AF highlighting the role of the pulmonary veins in AF development.
Abstract 18281: Soluble Form of Membrane Attack Complex Independently Predicts Mortality and Cardiovascular Events in Patients with ST-segment Elevation Myocardial Infarction
Authors: Søren Lindberg, Sune Pedersen, Rasmus Møgelvang, Søren Galatius, Allan Flyvbjerg, Jan S Jensen, Mette Bjerre
Journal: Circulation (2012)

Background: The complement system is an important mediator of inflammation, which plays a pivotal role in atherosclerosis and acute myocardial infarction (AMI). Animal studies suggest that activation of the complement cascade resulting in the formation of sMAC, contributes to both atherosclerosis and plaque rupture and may be the direct cause of tissue damage related to ischemia/reperfusion injury. However clinical data of sMAC during an AMI is sparse. Accordingly the aim was to investigate the prognostic role of soluble membrane attack complex (sMAC) in patients with ST-segment elevation myocardial infarction (STEMI). Methods: We included 725 STEMI-patients admitted to a single, high-volume invasive heart centre, treated with primary percutaneous coronary intervention (PCI), from September 2006 to December 2008. Blood samples were drawn immediately before PCI. Plasma sMAC was measured using an in-house immunoassay. Endpoints were all-cause mortality (n=62) and the combined endpoint (n=122) of major cardiovascular events (MACE) defined as cardiovascular mortality and admission due recurrent AMI or heart failure. Follow-up time was 12 months. Results: Patients with high sMAC (&gt;75 th percentile) had increased risk of all-cause mortality and MACE. Even after adjustment for confounding risk factors by Cox-regression analyses, high levels of sMAC remained an independent predictor of all-cause mortality (hazard ratio 1.81 (95% CI 1.06-3.06; p=0.029)) and MACE (hazard ratio 1.70 (95% CI 1.16-2.48; p=0.006)). Conclusions: High plasma sMAC independently predicts all-cause mortality and MACE in STEMI-patients treated with PCI.
Abstract 19596: Endothelial Acyl-CoA Synthetase 1 is not Required for Saturated Fatty Acid- Mediated Inflammatory and Apoptotic Effects
Authors: Oscar Gonzalez, Xin Li, Shelley Barnhart, Farah Kramer, Xia Shen, Anuradha Vivekanandan-Giri, Jenny E Kanter, Priya Handa, Subramaniam Pennathur, Subramaniam Pennathur, Francis Kim, Rosalind A Coleman, Jean E Schaffer, Karin E Bornfeldt
Journal: Circulation (2012)

Saturated fatty acids, such as palmitic (C16:0) and stearic acid (C18:0), cause detrimental effects in endothelial cells (ECs) that might contribute to macrophage accumulation in adipose tissue and the vascular wall in states of obesity and insulin resistance. Fatty acids require conversion into acyl-CoA derivatives to exert most biological effects, a reaction catalyzed by acyl-CoA synthetases (ACSL). We hypothesized that endothelial deficiency of ACSL1, an ACSL isoform mediating inflammatory effects in myeloid cells, would protect from detrimental effects of saturated fatty acids in vitro and saturated fat feeding in vivo. Mouse microvascular CD45-negative-CD31-positive endothelial cells (MMECs) were isolated from lungs or hearts by fluorescence activated cell sorting. In these cells and in bovine aortic ECs (BAECs), saturated fatty acids caused JNK activation, ER stress, and apoptosis, along with increased inflammatory activation, as measured by an increase in the release of the soluble adhesion molecules sICAM-1 (p&lt;0.01), and sVCAM-1 (p&lt;0.01), as well as release of the chemokine CCL2 (p&lt;0.05). In order to evaluate the role of endogenous ACSL1 in ECs, a conditional endothelial Acsl1-deficient mouse model was generated. Acsl1-deficient MMECs had significantly decreased beta-oxidation as measured by decreased acid soluble metabolite production (WT 393.1 ± 25.6, KO 270.5 ± 16.3 cpm/µg protein; p&lt;0.05). However, conditional endothelial ACSL1-deficiency did not protect against the inflammatory or apoptotic effects of saturated fatty acids in vitro, nor did it protect insulin resistant mice fed a saturated fatty acid-rich diet from epididymal adipose tissue accumulation of macrophages or increased aortic adhesion molecule expression. Conversely, forced Acsl1 overexpression in BAECs exacerbated the effects of saturated fatty acids on apoptosis and ER stress, in part through increased JNK activation. In conclusion, forced overexpression of Acsl1 can exacerbate some effects of saturated fatty acids; however, endogenous ACSL1 is not required for pro-inflammatory or pro-apoptotic responses of ECs to saturated fatty acids.