tbuckley/cabot-search huggingface dataset:
Abstract 19582: Deletion of miRNA-146a Alters Host Immune Response to Coxsackievirus B3 with Activation of NK cells
Authors: Anna Narezkina, Byung-Kwan Lim, Sergei Grivennikov, Mark Boldin, Konstantin Taganov, David Baltimore, Kirk U Knowlton
Journal: Circulation (2012)

Coxsackievirus B3 (CVB3) is a positive single-stranded RNA virus that causes a range of diseases, including myocarditis, hepatitis, and pancreatitis. Understanding complex interplay between the virus and host immune system will provide insight for development of future therapeutic interventions. miRNA-146a plays a role in immune system through regulation of NF-kB signaling. It is expressed at relatively high levels in hematopoetic cells, and upregulated with various immune stimuli. We hypothesized that miRNA-146a is involved in mediating immune response against CVB3 infection. Genetically modified C57BL/6 mice with global deletion of miRNA-146a, and wild type littermate controls were intraperitoneally injected with 10 3 -10 4 PFU of CVB3. miRNA-146a null mice had significantly higher mortality rate, reaching 45% by day 4 after infection (n=16), compared to zero mortality observed in wild type mice (n=13, p=0.006). Evans blue dye uptake was higher in the hearts of knock out animals 4 days post-infection, indicating disruption of cardiomyocyte membrane integrity. The degree of hepatocyte damage and disruption of the lobular architecture in liver was more pronounced in the miRNA-146a null mice 4 days post-infection. In normal uninfected state the majority of NK cells are localized in liver and spleen, and they are one of the first to get activated in CVB3 infection. We assessed the degree of NK cell activation 24 hours post infection with FACS analyses of mononuclear cells isolated from liver by Percoll gradient. The total percentage of NK cell population in liver was the same between both groups. On average 10+/-0.8% of total NK population in the livers of knock out mice were represented by the cells with high level of TNF-related apoptosis-inducing ligand (TRAIL) expression, whereas only 4.7+/-2% of the hepatic NK cells in the wild type controls had the same level of TRAIL expression (n=3, p=0.03). Liver mRNA levels of Granzymes A and B, and perforin were 4- to 8-fold higher in miRNA-146a null mice compared to wild type controls (n=6 for wild type, n=5 for knock out, p0.05). Taken together, these data indicate that deletion of miRNA-146a alters host response to CVB3 by increasing NK cell activation.
Abstract 212: Can Return of Spontaneous Circulation Be Achieved Faster in a Resuscitation Algorithm that Directs the Duration of Postshock Chest Compressions According to the Preshock Value of the Amplitude-Spectral Area? A Study of Ventricular Fibrillation Cardiac Arrest in Normal Swine
Authors: Meghan McGovern, Daniel Allen, Fahd Chaudhry, Ronald Hilwig, Karl B Kern, Julia Indik
Journal: Circulation (2012)

Background: It has been previously demonstrated in a swine model of cardiac arrest due to ventricular fibrillation (VF) that a return of spontaneous circulation (ROSC) following a shock is predicted by the amplitude spectral area (AMSA), a quantitative measure of the VF waveform. These prior studies were a retrospective analysis of the VF waveform prior to shocks. We hypothesize that AMSA can be utilized in a prospective fashion as part of a resuscitation algorithm to direct the duration of post-shock chest compressions (CC). Specifically, we have tested whether such an AMSA-directed algorithm will shorten the time needed to achieve ROSC in normal swine. Methods: VF was induced electrically in normal swine and untreated for 10 minutes. Resuscitation was commenced with 1 minute of CC, resumption of mechanical ventilation, followed by the first shock and administration of epinephrine. Subsequently, animals were randomized to a traditional or waveform guided group. In the traditional group, all shocks were followed by 2 minutes of post-shock CC. In the waveform guided group, AMSA was measured prior to each shock and if AMSA&gt;20 mV-Hz then post shock CC duration was shortened to 1 minute. ROSC was defined as a systolic aortic pressure greater than 50 mm Hg and pulse pressure &gt; 20 mm Hg lasting at least one minute. Time to ROSC was compared with a Kruskal-Wallis rank test. AMSA was compared between groups using regression analysis with random effects to account for multiple shocks within the same animal. Results: A total of N=8 animals were assigned to the traditional group with 22 shocks delivered, and N=8 animals to the waveform guided group with 21 shocks delivered. Time to ROSC (from induction of VF) was 14.5 ±1.2 minutes in the traditional group and 13.5± 1.2 minutes in the waveform guided group, (P=0.2). There was a trend for higher AMSA values in the waveform guided group: 48 ± 15 versus 39 ± 16 mV-Hz (P=0.1). Conclusions: A resuscitation algorithm that tailors the duration of post-shock chest compressions to the value of AMSA is feasible. In this study of normal swine we found small, but non-significant, reductions in the times to achieve ROSC and higher values of AMSA in swine treated with a waveform guided approach.
Abstract 56: Sodium Nitroprusside--Enhanced Cardiopulmonary Resuscitation Prevents Postresuscitation Left Ventricular Dysfunction and Improves 24-Hour Survival and Neurological Function in a Porcine Model of Prolonged Untreated Ventricular Fibrillation
Authors: Demetris Yannopoulos, Jason Schultz, Nicolas Segal, James Kolbeck, Emily Caldwell, Marit Thorsgard, Scott McKnite, Tom Aufderheide, Keith Lurie
Journal: Circulation (2011)

Background: Sodium nitroprusside-enhanced CPR, or SNPeCPR, consists of active compression decompression CPR with an impedance threshold device, abdominal compression, and intravenous sodium nitroprusside (SNP). We hypothesize that SNPeCPR will improve post resuscitation left ventricular function and neurological function compared to standard (S) CPR after 15 minutes of untreated ventricular fibrillation (VF) in a porcine model of cardiac arrest. Methods: Pigs (n=22) anesthetized with isoflurane underwent 15 minutes of untreated VF, were then randomized to 6 minutes of S-CPR (n=11) or SNPeCPR (n=11) followed by defibrillation. The primary endpoints were neurologic function as measured by cerebral performance category (CPC) score and left ventricular ejection fraction. Results: SNPeCPR increased 24-hour survival rates compared to S-CPR (10/11 versus 5/11, p=0.03) and improved neurological function (CPC score 2.5±1, versus 3.8±0.4, respectively, p=0.004). Left ventricular ejection fractions at 1, 4 and 24 hours after defibrillation were 72±11, 57±11.4 and 64±11 with SNPeCPR versus 29±10, 30±17 and 39±6 with S-CPR, respectively (p&lt;0.01 for all). Conclusions: In pigs, after 15 minutes of untreated VF, SNPeCPR significantly improved 24-hour survival rates, neurologic function and prevented post-resuscitation left ventricular dysfunction.
Abstract 9754: Individual-Level Cardiovascular Health Behavior and Health Factor Changes (1999-2008), Projections to 2020, and Comparisons with AHA 2020 Impact Goal Targets in US Men and Women: Results from the National Health and Nutrition Examination Surveys (NHANES)
Authors: Mark D Huffman, Simon Capewell, Hongyan Ning, Earl S Ford, Donald M Lloyd-Jones
Journal: Circulation (2011)

Introduction: A higher number of ideal health behaviors and health factors is associated with a substantial reduction in CV event rates. The AHA 2020 Impact Goals target a 20% relative improvement in overall cardiovascular (CV) health using 4 health behaviors (smoking, body mass index [BMI], physical activity, diet) and 3 health factors (cholesterol, blood pressure, plasma glucose). To date, there have been no studies to estimate future trends in individual-level CV health behavior/factor levels. Methods: We used data on CVD-free individuals from NHANES 2-year cycles (1999-2000, 2001-2, 2003-4, 2005-6, 2007-8) to estimate the number of poor, intermediate, and ideal health behaviors/factors per individual for men and women. We created a composite, individual-level CV health score for all 7 metrics (poor=0 points; intermediate=1 point; ideal=2 points; total scale: 0-14 points) and performed age-adjusted weighted linear regression models to produce β coefficients and forward projections to 2020. We compared these forward projections based on current trends with a 20% relative increase (based on the AHA Goal) in the composite CV health score from 2006 to 2020. Results: The mean number of ideal health behaviors/factors within individual men and women has not significantly changed from 1999 to 2008 (Table 1). The mean CV health score in men increased from 7.5 (1999-2000) to 7.7 (2007-8), but the test for trend was not significant ( β = 0.01, p=0.67); the mean CV health score was higher in women (7.9 in 1999-2000; 8.1 in 2007-8), but the test for trend was also not significant ( β = 0.02, p=0.06). Assuming current trends continue, CV health score projections to 2020 for men (7.7 [95% CI 5.9, 9.5]) and women (8.3 [95% CI 8.0, 8.6]) would not achieve a 20% overall change in the composite score (men: 8.8; women: 9.6). Conclusions: These data suggest that the AHA 2020 Impact Goals to improve CV health by 20% will not be met for individuals if current health behavior/factor trends continue.
Translational Medicine in Atherosclerosis: From Human Genetics to New Biology to Novel Therapeutics
Authors: Daniel J. Rader
Journal: Circulation (2012)

Despite advances over the last few decades, atherosclerotic cardiovascular disease (ASCVD) remains a major public health issue worldwide. New therapies for the prevention and treatment of ASCVD are still needed. The investigation of monogenic disorders, such as those associated with extremes of plasma lipids, have yielded new therapeutic targets and spurred the development of new therapeutic approaches. Unbiased genome-wide studies have identified a large number of novel genetic loci associated with different manifestations of ASCVD (eg. myocardial infarction and obstructive CAD) as well as risk factor traits (eg. plasma lipids). These discoveries are beginning to result in new insights into biology and physiology relevant to the development of ASCVD. For example, a locus on chromosome 1p13 was found to be significantly associated with MI, as well as noted to be one the strongest loci in the genome associated with LDL cholesterol. The causal gene at this locus, SORT1, encodes a protein sortilin that through action in the liver has important effects on LDL metabolism. Several other loci associated with plasma lipid traits have yielded new insights into the regulation of lipoprotein metabolism. Similarly, loci associated with MI and CAD are putting new molecules on the map that causally influence the development of atherosclerosis or plaque disruption. Just as the study of monogenic disorders has yielded new therapeutic targets, it is expected that translation of the new biology unfolding as a result of genome-wide studies of ASCVD and its risk factors will ultimately yield novel therapies for the treatment of atherosclerotic disease.
Abstract 9864: Depression Inhibits the Positive Effects of Exercise and Light-to-Moderate Alcohol Consumption on C-Reactive Protein Levels
Authors: Edward C Suarez
Journal: Circulation (2012)

Introduction: Light to moderate alcohol consumption and exercise are associated with lower cardiovascular mortality and levels of high sensitivity C-reactive protein (hsCRP), a predictor of cardiovascular risk. In contrast, depression is associated with higher cardiovascular risk and hsCRP. We tested the hypothesis that depression attenuates the positive effects of exercise and alcohol consumption on hsCRP. Methods: Data were collected on 225 adult men and women (18-65 yrs, 45% women, 40% minorities). The Beck Depression Inventory (BDI) was administered the same day blood samples were collected for hsCRP. BDI scores &gt; 9 indicated depression. The following was used to classify alcohol consumption: never/former (&lt; 1 drink in past 12-months), infrequently (1-3 drinks/month), occasionally (1-7 drinks/week), and regularly (2 drinks/day). Multivariate models were used to test the interaction effects on log-transformed CRP. Results: Depression was noted in 20% of participants. Adjusting for a number of coronary risk factors, depression attenuated the effect of exercise on hsCRP (p = .043). Among those who exercised (n = 184), hsCRP was higher in depressed versus non-depressed subjects (p = .005). No gender differences were noted. Depression also attenuated the effect of alcohol consumption on hsCRP in men but not women (p = .006). Among women who abstained (n = 29), those who were depressed exhibited higher hsCRP compared to non-depressed women (p = .03). Depression did not affect hsCRP in women who drank. In non-depressed men (n = 102), drinkers exhibited lower hsCRP relative to non-drinkers (p &lt; .05). In depressed men (n = 19), however, the positive effect of alcohol consumption was not observed. This was most notable among men who reported occasional and regular alcohol use (n= 55), where depressed men exhibited significantly higher hsCRP than non-depressed men (p = .005). Conclusions: Independent of cardiovascular risk factors, current depression inhibits the positive effects of exercise on hsCRP. In men, but not women, depression also attenuates the effect of light-to-moderate alcohol intake on hsCRP. Combined, these data suggest the potential for depression to attenuate the health benefits of cardioprotective factors.
Abstract 14357: A Reproducible Porcine Model of Thoracic Aortic Aneurysm
Authors: Shaina R Eckhouse, Risha K. Patel, Allison D. Rice, Christina B. Logdon, J. Marshall Oelsen, Robert E. Stroud, William B. Wince, Rupak Mukherjee, Francis G. Spinale, John S. Ikonomidis, Jeffrey A. Jones
Journal: Circulation (2012)

Shaina R Eckhouse, 2012 Finalist and Presenting Author
Abstract 9738: Use of the Syntax Score In Predicting Outcome After Unrestricted Use of 'limus' Stents
Authors: Jeehoon Kang, Kyung Woo Park, Si-Hyuck Kang, Hyo-Suk Ahn, Hae-Young Lee, Hyun-Jae Kang, Bon-Kwon Koo, In-Ho Chae, Tae-Jin Youn, Byung-Hee Oh, Young-Bae Park, David Kandzari, Hyo-Soo Kim
Journal: Circulation (2012)

Background The SYNTAX score (SS) and clinical SS (cSS) are widely used to assess coronary lesion complexity, and are useful indices in predicting outcomes after percutaneous coronary intervention. However, SS was derived from a study that exclusively used paclitaxel eluting stents, and its applicability to patients receiving ‘limus’ eluting stents is unclear. Thus, we investigated the validity of the SS and cSS in predicting clinical outcomes from a cohort where ‘limus’ stents were used unrestrictedly. We also compared the predictability of the scores in everolimus eluting stents (EES) versus sirolimus eluting stents (SES). Methods Patients were from the Efficacy of Xience/Promus versus Cypher in rEducing Late Loss after stenting (EXCELLENT) registry and the SS was evaluated at an independent angiographic core lab. The 1-year patient oriented composite endpoint (POCE) (all cause death, any myocardial infarction (MI), and any revascularization) and target lesion failure (TLF) (cardiac death, target vessel MI, and target lesion revascularization) were the major analysis endpoints. The area under the curve (AUC) of a receiver operating characteristic was used as the predictability of SS and cSS. Results Among 5102 patients (7003 lesions) enrolled, 3047 patients (4235 lesions) received EES and 2055 patients (2768 lesions) received SES. Tertiles for SS were defined as low SS&lt;8, 8≤mid SS≤16, high SS&gt;16. From the whole population, both POCE (4.2% vs. 7.7% vs. 12.2%, p&lt;0.001) and TLF (1.6% vs. 2.4% vs. 4.5%, p&lt;0.001) increased significantly along with increasing SS tertiles, and SS was an independent predictor of POCE and TLF in multivariate analysis (p&lt;0.001 for all) The predictability of SS and cSS was similar for POCE (AUC: 0.635 vs. 0.629, for SS vs. cSS, p=0.599) but cSS was superior to SS in predicting TLF (AUC: 0.625 vs. 0.680, for SS vs. cSS, p=0.008). When stratified according to each stent, higher SS tertiles were significantly associated with increased risk of POCE and TLF in both EES and SES. Conclusion Both SS and cSS were applicable to unrestricted use of ‘limus’ stents to predict the risk of 1-year adverse clinical outcomes. The predictability of SS and cSS was similar for POCE but the inclusion of clinical variables improved predictability of the SS for TLF.
Abstract 9: Total Liquid Ventilation Provides a Combined Neuro- and Cardioprotection After a Shockable Cardiac Arrest Occurring After Regional Myocardial Ischemia in Rabbits
Authors: Lys Darbera, Mourad Chenoune, Fanny Lidouren, Matthias Kohlhauer, Clovis Adam, Patrick Bruneval, Pierre Carli, Benoît Vivien, Jean-Damien Ricard, Jean-Luc Dubois-Randé, Bijan Ghaleh, Alain Berdeaux, Renaud Tissier
Journal: Circulation (2012)

Introduction: Total liquid ventilation (TLV) with perfluorocarbons has been shown to induce a rapid and protective cooling in animal models of cardiac arrest (CA). In these models, the heart was arrested without underlying myocardial ischemia. Hypothesis: We assessed whether TLV could provide a combined neuro- and cardioprotection after a CA occurring after previous myocardial ischemia, as commonly observed in the clinical arena. Methods: Rabbits instrumented with cardiac output (CO) probes were submitted to coronary artery occlusion. Two minutes later, ventricular fibrillation was induced and let untreated during 8 min. Rabbits were subsequently resuscitated and randomly submitted to a normothermic follow-up (Control) or 3 h of hypothermia (32°C) with either TLV or external cold blankets combined to saline infusion (30 ml/kg at 4°C i.v.; Saline group). Coronary artery reperfusion was instituted after 40 min of myocardial ischemia. After awakening, surviving rabbits were followed during 7 days. Results: Ten rabbits were included and resuscitated in each group. Under cooling, the target tympanic and esophagus temperatures of 32°C were achieved within 5-10 min in TLV vs 30-45 min in Saline group. In the latter group, hypothermia failed to improve subsequent survival, CO or neurological recovery but slightly reduced infarct size vs Control (41±5% vs 54±3% of risk zone, respectively). Conversely, TLV potently reduced infarct size (13±1% of risk zone) and improved CO (e.g., 133±11 vs 84±19 ml/min/kg in survivors at day 1 in TLV vs Control, respectively). As shown in Figure, TLV also improved survival and neurological outcome. Conclusions: Ultra-fast cooling with TLV induced a potent cardio- and neuroprotection in a rabbit model of CA with underlying myocardial ischemia, whereas conventional hypothermia was less efficient. Left: Neurological dysfunction score (0%: normal; 100%: death). Right: survival after the cardiac arrest.*, p&lt;0.05 vs Saline and Control
Abstract 19154: A Combinatorial Approach for Bone Marrow Stem Cell Mobilization, Homing-in and Retention for De Novo Cardiac Regeneration: Gcsf Treatment Combined with Ex Vivo Transgenic Sdf-1α Delivery in the Heart
Authors: Shujia Jiang, Christy M Caudill, Rafeeq P Ahmed, Haider H Khawaja
Journal: Circulation (2012)

Objective: We have already shown that bone marrow stem cells (BMC) mobilized into the infarcted heart developed into mature cardiomyocytes and improved the heart function. Granulocyte colony stimulating factor (GCSF) reduces stromal cell derived factor-1 α (SDF-1α) in the bone marrow to support extravasation of BMC from their niches. We hypothesized that GCSF treatment combined with a favorable SDF-1α gradient in the infracted heart would promote homing-in and retention of mobilized BMC for angiomyogenic repair of the infracted myocardium. Methods and Results: Radiomyoabalated young female Fisher 344 rats received 1×10 6 BMC from transgenic GFP + male rats. Two month later, animals were used to develop experimental model of acute LAD artery ligation. The animals were grouped (n=16) to receive following intramyocardial injection of 70μ l DMEM without cells (G1) or containing 1×10 6 wild type BMC with (G2 and G3) or without SDF-1α overexpression (G4). Besides G1 and G3 had intraperitoneal injection of DMEM without GCSF whereas G2 and G4 received 10µg/kg body weight GCSF treatment starting 3 days prior to and until 2 days after intramyocardial injection of cells. Animals were harvested 4 days and 4 weeks after their respective treatment and the hearts were removed for molecular and histological studies. SDF-1α expression was higher in G2 and G4 animal hearts ( p &lt;0.05 vs all groups) on day 4 with. Highest mobilization of GFP + BMC was observed in and around the infarcted myocardium in G2. GFP + BMC were also identified by immunostaining for ckit, CXCR4 and CD44 which showed highest propensity in G2. Fluorescence immunostaining for GFP and cardiac actin at 4 weeks showed that mobilized cells extensively differentiated into mature muscle fibers. Similarly, vascular density was markedly increased in G2 ( p &lt;0.01 vs all groups) in peri-infarct area. Infarct size was significantly attenuated with improved LV contractile function in G2 ( p &lt;0.05 vs all groups). Conclusions: Concomitant ex vivo expression of SDF1α in the infarcted heart combined with intraperitoneal GCSF treatment is more effective and efficient approach to mobilize BMC for participation in myocardial repair. Mobilized BMC homed-in to the infarcted heart and supported extensive angiomyogenic repair.
Abstract 9771: Aggressive Treatment of Cardiovascular Risk Factors: Effects on Atherosclerosis and Arterial Age
Authors: Matthew D Wilson, Cheryl A Gibson, Sara D Powell, James M Backes, David Eldringhoff, Patrick M Moriarty
Journal: Circulation (2012)

Background: Atherosclerosis, the major cause of cardiovascular disease (CVD), involves the abnormal deposit of cholesterol within the intima of the arterial wall. Arteriosclerosis is the annual thickening (roughly 0.01 mm per year) of the arterial wall (media) based generally on aging. An indirect method of diagnosing atherosclerosis involves ultrasound analysis of the common carotid intima-media wall thickness (CCIMT) to evaluate a patient's arterial age. Arterial age is a term representing the combination of wall thickness based both on atherosclerosis and arteriosclerosis. Hypothesis: Aggressively treating CVD risk factors will reduce atherosclerosis and arterial age as measured by CCIMT analysis. Methods: An observational study of 220 patients (121 m, mean age 58 yrs) treated in a CVD prevention clinic and with at least 1 CVD risk factor. Two ultrasounds were performed by the same sonographer, approximately 3 years apart, with a computerized edge-detection device (MICROMAXX, Sonosite) measuring 100 markers within 1 cm area of the CCIMT wall, 1 cm proximal to the bulb, to provide the maximum thickness. Arterial age was estimated based on data of previous epidemiology studies stored within the MICROMAXX. Results: After a mean follow up of 3.05 years, the observed values for maximum CCIMT (see table) were significantly lower (p&lt;0.0001) than expected. While patients' chronological age increased by 3 years, their arterial age decreased by 1.53 years (p&lt;0.0001), translating into a 4.57 year difference compared to the expected change. Reduction of total cholesterol was the only risk factor found to be significantly associated with reduction in vascular age (p&lt;.027). Conclusion: In patients with CVD risk factors, aggressive clinical treatment resulted in statistically significant reductions in the rate of maximum CCIMT progression and reversing arterial age. Longer follow-up is needed to determine if these findings also translate to fewer clinical events.