tbuckley/cabot-search huggingface dataset:
Abstract 323: Intra-arrest Induction of Preferential Brain Cooling With Mild Systemic Hypothermia Does Not Correlate With Favorable Outcome in a Rabbit Model of Ventricular Fibrillation
Authors: Jun Guan, Mengyuan Diao, Zhaofen Lin, Zhe Zhang, Yan Xiao
Journal: Circulation (2013)

Introduction: Recent reports suggested that poor clinical outcomes correlate with rapid cooling in cardiac arrest patients. The possible causes are unclear. We have now compared survival between intra-arrest induction of preferential brain cooling with mild systemic hypothermia and conventional surface cooling animals, and focused on the relationship between hemodynamics and brain temperature (Tb). Methods: Untreated VF of 4 min and CPR of 4min were given to 24 rabbits prior to defibrillation. Animals were randomly assigned to (1) preferential brain cooling by a neck cooling collar initiated at beginning of CPR, (2) body surface cooling by ice pads and fan initiated at 30 min after ROSC, (3) spontaneous normothermia control. Core body temperature (Tc) and Tb were monitored by thermoprobes in rectum and brain parenchyma respectively. Mean aortic pressure (MAP), heart rate (HR), LV dp/dt, LV -dp/dt, and PetCO2 were continuously monitored. During 4 hrs of cooling, Tc was maintained between 33.5°C and 34.5°C by turning on/off the cooling regardless Tb. Cooling would also be paused if MAP is below 60 mmHg. Methods for control animals were identical except for cooling. Results: Six of 8 animals in each group achieved ROSC and survived to 18±17, 17±18, and 21±23 hrs after ROSC respectively, P=0.921. First time pause of cooling due to low MAP only occurred in all 6 brain cooling animals. At first pause of cooling, Tb and Tc were 34.1±0.8°C and 33.5±0.2°C in body cooling animals, but were 29.2±1.3°C and 35.5±0.9°C in brain cooling animals respectively. MAP and HR in brain cooling animals were significantly lower than those in body cooling and control animals at 30min, and 60 min after ROSC (Table). Linear regression analysis showed that Tb but not Tc was the independent influential factor for MAP after ROSC. Conclusions: Early induction of preferential brain cooling does not necessarily improve outcome after ROSC. Hypotension correlates with low Tb and warrants close monitoring and management.
Abstract 9333: Prognostic Value of Stress Echocardiography In Patients Achieving a High Exercise Workload (=10 Metabolic Equivalents) and Submaximal Heart Rate Response
Authors: Siu-Sun Yao, Vikram Agarwal, Azhar Supariwala, Farooq Chaudhry
Journal: Circulation (2013)

Background: High exercise capacity (≥10 metabolic equivalents, METS) is a predictor of favorable prognosis. Submaximal studies (&lt;85% maximum predicted heart rate, MPHR) may lead to non-diagnostic results and indeterminate outcomes. The purpose of this study was to examine the prognostic value of stress echocardiography (SEcho) in patients achieving high exercise capacity and submaximal heart rate response. Methods: We evaluated 81 patients (50 ± 13 years; 62% male) achieving nine minutes (≥10 METS) and &lt;85% MPHR with treadmill SEcho. Resting left ventricular ejection fraction and regional wall motion were assessed. The left ventricle was divided into 16 segments and scored on 5-point scale of wall motion. Abnormal SEcho was defined as stress-induced ischemia (wall-motion score of ≥1 grade). Followup (3.4 ± 1.5 years) for non-fatal myocardial infarction and cardiac death (n = 2) were obtained. Results: By univariate analysis, the number of new ischemic wall motion abnormalities (hazard ratio = 2.5, confidence interval 1.2 - 5.3, p = 0.02) was the most significant predictor of cardiac events. Cumulative survival in patients achieving nine minutes (≥10 METS) and &lt;85% MPHR was significantly worse in patients with abnormal (ischemic) vs. normal (nonischemic) SEcho (1.1%/year vs. 0.2%/year, p = 0.02)[Graph]. Conclusions: The ability to achieve nine minutes (≥10 METS), despite &lt;85% MPHR by treadmill SEcho was associated with a benign prognosis (~1.0%/year). In the setting of high achieved exercise capacity and &lt;85% MPHR, SEcho results (presence or absence of ischemia) were further able to sub-stratify this low risk group.
Abstract 71: Comparison of Outcome of Extracorporeal Cardiopulmonary Resuscitation for Out-of-Hospital and In-Hospital Cardiac Arrest
Authors: Yih-Sharng Chen, Nai-Kwoun Chou, Chih-Hsien Wang, Jou-Wei Lin, Hsi-Yu Yu, Nai-Hsin Chi, Shu-Chien Huang, Shoei-Shen Wang, Lance Becker
Journal: Circulation (2013)

Objectives: The aim of this study was to investigate the effects of extracorporeal cardiopulmonary resuscitation (ECPR) for out-of-hospital cardiac arrest (OHCA) and compare the results with those of in-hospital cardiac arrest (IHCA). Background: ECPR, considered an adjuvant therapy for IHCA, has been previously applied for OHCA with unsatisfactory results. Methods: We reviewed our prospectively collected extracorporeal membrane oxygenation (ECMO) results and analyzed the data for patients who received ECPR for OHCA or IHCA in the last 5 years. Pre-arrest, resuscitation, and post-resuscitative data were evaluated. Results: In the last 5 years, ECPR was used 230 times for OHCA (n=31) and IHCA (n=199). The basic demographic data showed significant differences in age, cardiomyopathy, and location of the initial CPR. Duration of ischemia was shorter in the IHCA group (44.4 ± 24.7 min vs. 67.5 ± 30.6 min, p 0.05). Survival was acceptable (about 33%) in both groups when the duration of ischemia was no longer than 75 minutes. Conclusions: In addition to having a beneficial effect in IHCA, ECPR can result in an acceptable survival and neurological outcome in selected OHCA patients after prolonged cardiopulmonary resuscitation. Our results suggest that further investigation of the use of ECMO in OHCA is warranted and that ECMO may be an effective adjuvant therapy.
Abstract 9253: A Randomized Controlled Trial of the Effects of Vitamin D Supplementation on Central Blood Pressures and Aortic Stiffness in Native American Women
Authors: Adam D Gepner, Irina V Haller, Diane C Krueger, Claudia E Korcarz, Neil C Binkley, James H Stein
Journal: Circulation (2013)

Background: Low vitamin D status has been linked to increased cardiovascular disease (CVD) risk. Low vitamin D levels, hypertension, and CVD are highly prevalent in Native American populations. However, it is unclear if vitamin D supplementation improves central blood pressure or arterial stiffness in Native American women. Methods: Healthy postmenopausal Native American women without known CVD and with screening serum 25-hydroxyvitamin D (25(OH)D) between 10-60 ng/mL were randomized to receive daily vitamin D3 either 400 IU or 2,500 IU for 6 months. Central systolic blood pressure (cSBP), central pulse pressure (cPP) and aortic augmentation index (AIx) were estimated by tonometry (AtCor Medical, Sydney, Australia) at baseline and after 6 months of vitamin D supplementation. General linear models were used to evaluate cross-sectional and longitudinal associations. Repeated measures models were adjusted for baseline 25(OH)D. Results: At baseline, study volunteers (n=98) were mean (standard deviation) 61 (7.3) years old. Screening 25(OH)D was 26.4 (11.0) ng/mL; 25(OH)D was less than 20 ng/mL in 33 (34%) participants and between 20-30 ng/mL in 29 (29.6%) participants. Screening 25(OH)D was similar between the two treatment groups (p=0.291), as were baseline cSBP, cPP, age, body-mass index, glucose, lipids, and high sensitivity C-reactive protein levels (all p&gt;0.1). Screening 25(OH)D was associated with cSBP (p=0.022) and cPP (p=0.007), but not AIx (p=0.807). Treatment with 2,500 IU of daily vitamin D3 did not affect cSBP (p=0.546), cPP (p=0.614), or AIx (p=0.103) compared to 400 IU daily. Conclusions: Despite relatively low serum 25(OH)D at baseline, 6 months of vitamin D supplementation did not improve central blood pressure parameters or arterial stiffness in Native American women.
Calcium: Nodal Regulator of Contractility and Hypertrophy in Cardiac Myocytes
Authors: Steven Houser
Journal: Circulation (2013)

This lecture will discuss Calcium (Ca 2+ ) influx pathways involved in the regulation of cardiac contractility and cardiac responses to pathological stress. The lecture will review the data showing that the persistent increases in Ca 2+ influx required for myocytes that have persistently increased contractile demands can induce pathological cardiac myocyte hypertrophy and can induce myocyte death signaling pathways. The respective sources of Ca 2+ that activate contractile proteins (to produce enhanced force development) and hypertrophic or death signaling cascades will be discussed. Recent data suggests that the sources of Ca 2+ for regulation of contractile function and hypertrophy signaling are distinct. L-type Ca 2+ channels (LTCCs) and Transient Receptor Potential (TRP) channels appear to be sources of Ca 2+ for signaling and LTCCs are the primary source of Ca 2+ to activate excitation contraction coupling. The idea that TRP and LTCCs are housed in cellular microdomains to locally activate partner proteins that lead to either contraction or activation of signaling cascades will be discussed. Data to be presented suggests that housing the same molecules, LTCCs and TRP channels, in separate membrane microdomains allows the same class of ion channels to affect either excitation contraction coupling or signaling partners.
Abstract 9424: Coronary Artery Disease-Related Death May Be Associated With Higher Critical Plaque Wall Stress: A Multi-Patient 3D Fluid-Structure Interaction Study Comparing Plaque Wall Stress, Flow Shear Stress, and Plaque Burden as Risk Indicators
Authors: Xueying Huang, Chun Yang, Jie Zheng, Richard Bach, David Muccigrosso, Pamela K Woodard, Dalin Tang
Journal: Circulation (2013)

Introduction: Plaque burden has been used to predict cardiovascular events. However, many patients without flow-limiting atherosclerosis and without prior symptomatology develop catastrophic syndromes including stroke, or sudden cardiac death. We hypothesized that plaque wall stresses play an important role in vulnerable plaque rupture and may serve as a risk factor for cardiovascular event. The objective of this study was to compare plaque wall stress, flow shear stress, and plaque burden and identify their possible association with coronary artery disease (CAD)-related death. Methods: Ex vivo MRI data of coronary plaques from 12 patients (6 died from CAD cause and 6 died from non-CAD cause, based on autopsy reports) were used to construct 3D fluid-structure interaction models. Plaque wall stress and flow shear stress were extracted from all nodal points on the lumen surface of each 3D plaque model for analysis. The maxima of plaque wall stress and flow shear stress from all local maxima (excluding those on healthy sites) of each plaque were defined as the 3D critical plaque wall stress (CPWS) and 3D critical flow shear stress (CFSS), respectively. Plaque burden was calculated as plaque+media area/total vessel area bounded by the out-boundary. Two-sided Student t-test was used to compare the difference of CPWS, CFSS and plaque burden between the CAD and non-CAD groups. Results: Table 1 shows that mean 3D CPWS from CAD Group was 94.3% higher than that from non-CAD Group (265.6 vs. 136.7 kPa, P=0.0029). No difference was found for 3D CFSS values (p=0.851) and plaque burden (p=0.552) between the two groups. Conclusion: The results showed that plaques from the CAD group were associated with higher critical plaque wall stresses compared with plaques from the non-CAD group, suggesting that CPWS may serve to predict event risk, and may provide more accurate plaque vulnerability assessment. Prospective and large-scale studies are needed to further validate our findings.
Abstract 85: Development of a Readily Translatable Model of Resuscitation From Ischemic Cardiac Arrest to Assess Regional and Global Arrhythmia Substrates and Outcomes
Authors: Aurelia Cheng, Hide Fukaya, Lance Wilson, Joseph S Piktel
Journal: Circulation (2013)

Background: Little is known about the effect of therapeutic hypothermia (TH) on arrhythmias in the resuscitated heart. TH has a beneficial effect on defibrillation thresholds and ROSC. However, there are no studies investigating why TH might be anti-arrhythmic during resuscitation from ischemia-induced cardiac arrest, the most common clinical scenario. Our goal was to develop a novel translational porcine model of resuscitation from regional ischemia-induced VF with the ability to identify differences in both regional and global arrhythmia substrates in order to determine mechanisms of the antiarrhythmic effect of TH and improve outcomes. Methods: Pigs underwent anesthesia and thoracotomy, and a large LAD occlusion was made. VF was induced after 30 min if spontaneous VF did not occur. CPR was started after 8 min with defibrillation and cardiac massage to achieve ROSC. Infarct was continued for a total of 60 min then reperfusion was continued for 60 min. Electrograms (EG) were recorded from multipolar needle (transmural) plunge electrodes at multiple sites and monophasic action potential (MAP) recordings were used to determine transmural and regional heterogeneities of repolarization and conduction. All spontaneous arrhythmias were recorded. Outcomes were compared between control (temp 37oC, CT), Pre-ischemia TH (TH 33oC), and post-infarct TH (TH-infarct). Cooling was induced using a cooling blanket, cold saline IV infusion, and ice packs. Results: Hemodynamic parameters were recorded during ischemia, during CPR, and reperfusion. Appropriate CPR was verified by BP and CO2 monitoring. 2/4 animals survived to the end of protocol in the CT group, 4/5 in the TH group, and 0/2 in the TH-infarct group. Total ROSC time was 9.8±7 for CT vs 37.5±6 (p&lt;.04) for TH group (no ROSC for TH-infarct). EG’s were used to assess activation recovery intervals at transmural sites in the infarct, noninfarct, and border zones. Regional VF waveforms were obtained. Conclusions: We developed a translatable model of resuscitation from ischemic cardiac arrest using regional and global electrophysiologic monitoring to assess arrhythmia substrates. These data suggest improved outcomes during resuscitation with TH.
Abstract 9244: A Novel Phosphorylating Mechanism of STAT3 in Protection against Ischemia/reperfusion by Pharmacological Preconditioning With Tadalafil, a PDE Inhibitor
Authors: Sanjay Kumar, Motoi Okada, Dehua Chang, Muhammad Ashraf
Journal: Circulation (2013)

Background: Phosphodiesterase (PDE) inhibition enhances Protein Kinase G-I (PKG-I) activity leading to stem cell survival and cardioprotection against ischemia/reperfusion injury. We previously reported phosphorylation of STAT3 ser727 during late phase of protection. We aimed to investigate the specificity of STAT3 in regulation of PKG-I and cardioprotection using heart specific conditional knockout mice. Methods and Results: Heart specific conditional knockout mice were made by breeding STAT3fl/fl with tamoxifen inducible cre (MCM) transgenic mice. MCM transgene was cloned downstream to heart specific myosin heavy chain promoter (MHC). Cre positive mice (MCM:STAT3fl/fl) were selected from genotyping and tamoxifen (20mg/kg) was administrated for 10 days. KO mice were pretreated with tadalafil (1mg/kg) 1h before LAD coronary artery ligation for 30 min followed by reperfusion. Echocardiographic analysis showed abrogation of cardioprotection in STAT3 knockout mice with decreased ejection fraction and fraction shortening as compared to non-transgenic mice. Mitogen activated protein kinases ERK and P38 were known to phosphorylate STAT3 at ser727. On contrary, western blot analysis with heart tissue lysate showed reduced phosphorylation/activation of ERK both in control and tadalafil treated cells with no change in total ERK (P&lt;0.05). Expression of pP38 and total P38 (p&lt;0.01) were unaltered. Two fold increase in expression of PKG-I (P&lt;0.05) during the late phase of protection was observed with tadalafil. Inhibition of PKG-I with KT5823 or antisense abolished STAT3 phosphorylation at ser727. Results were also replicated in vitro with mesenchymal stem cells isolated from adult male Fischer-344 rats by flushing the cavity of femur and cultured, purity was checked by CD44+ and CD73+ surface markers (flow cytometry). Cells were pretreated 1 h with tadalafil (100μM) then subjected to 2 h hypoxia (1% O2) and reoxygenation for 2 h/24 h. Conclusion: The study showed novel mechanism of phosphorylating STAT3 at ser727 by PKG-I leading to its entry inside nucleus and transcriptional activation of PKG-I by binding onto promoter making it a positive feedback loop. Heart specific STAT3 knockout mice showed abrogation of cardioprotection with tadalafil.
Abstract 9416: Undiagnosed Peripheral Arterial Disease (PAD) is Common in Patients Referred for Stress Tests Without a History of Atherosclerotic Heart Disease
Authors: Amar Narula, Alana Choy Shan, Ricardo Benenstein, Matthew Konigsberg, Daisy Duan, Larry Phillips, Muhamed Saric, Harmony R Reynolds
Journal: Circulation (2013)

Background: The ankle brachial index (ABI) is a highly sensitive and specific method to diagnose peripheral arterial disease (PAD). Abnormal ABI (≤0.9 or ≥1.4) predicts cardiovascular events and mortality, independent of traditional risk factors. Post-exercise ABIs can identify additional individuals with hemodynamically significant PAD. METHODS: ABI was measured at rest and immediately post-exercise in patients referred for stress testing without known carotid, coronary, or peripheral atherosclerotic disease. ABI was classified as normal (1-1.39), borderline (0.91-0.99), low (≤0.9), or consistent with poorly compressible arteries (≥1.4). Abnormal post-exercise ABI was defined according to guidelines as a ≥20% decrease in ABI or a decline in ankle systolic blood pressure of ≥30 mmHg. ABIs were measured using automated oscillometric cuffs, which correlate well with Doppler and have excellent specificity. RESULTS: 223 patients were enrolled in this ongoing study at the time of analysis, 108 of whom had post-exercise measurements. At rest, 20/223 (9%) had poorly compressible arteries, 7/223 (3.1%) had borderline ABI, and 1/223 (0.5%) had low ABI. Of those with normal ABI for whom post-exercise ABI was obtained, 34/108 (31.5%) had abnormal post-exercise ABI. Among patients with PAD by ABI, rates of use of aspirin (12/35), statins (9/35), and ACE-inhibitor/angiotensin receptor blockers (10/35) were low. Only 2 of 35 patients diagnosed with PAD had abnormal stress tests. 12 of the 223 patients overall had positive stress tests for ischemia. CONCLUSIONS: ABI measurement in patients referred for stress testing led to a diagnosis of peripheral vascular disease (poorly compressible arteries or PAD) in 24.6% of patients, despite low rates of ischemia on clinically indicated stress tests. ABI screening in this patient population may improve our ability to target use of guideline-recommended therapies for the prevention of cardiovascular events.
Abstract 87: Lactate and Need for Vasopressors Predicts Mortality After Out-of-Hospital Cardiac Arrest
Authors: Michael N Cocchi, Brian Saindon, Tyler Giberson, Parth V Patel, Michael W Donnino
Journal: Circulation (2013)

Background: Early prediction of outcome after out of hospital cardiac arrest (OHCA) is difficult. Previous work has indicated that the combination of lactate and the need for vasopressors may stratify patients and predict outcome. Hypothesis: The combination of initial lactate and requirement for vasopressor support will predict survival post-arrest. Methods: To validate previous retrospective findings, we conducted a prospective observational study of all OHCA (age &amp;gt18, non-traumatic) patients presenting to the emergency department of a tertiary care center between June 2006 and July 2013 with ROSC. We conducted a logistic regression model with hypotensive status (yes or no) and lactate level (lactate &amp;lt5, between 5-10 mmol/L and &amp;gt10) as predictors of mortality. Results: A total of 140 patients were enrolled. Median age of the cohort was 67 (IQR: 53-79.) 72% underwent mild therapeutic hypothermia. Overall mortality rate for the cohort was 60.71%. Patients who received vasopressors had a significantly higher mortality rate than those who did not receive vasopressors (69.4% v. 47.3% ; p=0.009). There was a step-wise increase in mortality associated with increasing lactate levels (37.0% lactate &amp;lt5, 68.8% lactate 5-10, 95.5% lactate &amp;gt10; p=0.0001). The AUC for our model was 0.76. Adjusting for hypotensive status, higher lactate levels were associated with increased odds of death compared to lactate 5-10 as the reference group (lactate 5-10 OR = 3.4, 95%CI: 1.6, 7.4; lactate &amp;gt10 OR = 30.9, 95%CI: 3.8, 249.4). When adjusting for lactate level there was no significant increase in odds of death for patients who were hypotensive compared to patients who were not hypotensive (OR=0.541, 95%CI: 0.3, 1.2). Conclusion: In this prospective validation of a previously retrospective finding, the combination of lactate and need for vasopressors in the immediate post-arrest period is predictive of mortality. Future multicenter validation of this tool is warranted.
Abstract 4: Initial Results for Pre-Hospital Transfusion of Plasma and RBCs in Trauma Patients
Authors: John B Holcomb, Daryn P Donathan, Deborah J del Junco, Georgian Brown, Toni von Wenckstern, Jeanette M Podbielski, Elizabeth A Camp, Rhonda Hobbs, Yu Bai, Michelle Brito, Elizabeth Hartwell, Bryan A Cotton, Charles E Wade
Journal: Circulation (2013)

Introduction: Earlier use of plasma has been associated with improved survival in trauma patients with substantial hemorrhage. In September 2011 we placed 2 units each of thawed plasma and RBCs on our helicopters. We hypothesized that pre-hospital transfusion (PHT) of thawed plasma and/or RBCs would result in improved patient coagulation status on admission and survival. METHODS: Adult trauma patient records were reviewed for patient demographics, shock, coagulopathy, outcomes and blood product utilization from Sept 2011-Dec 2012. Patients arrived by either ground or two different helicopter companies. All patients transfused blood products (either pre or in-hospital) were included in the study. One helicopter system had thawed plasma and RBCs while the other air and ground transport systems used only crystalloid resuscitation. Patients receiving PHT were compared with all other patients meeting entry criteria to the study cohort. All comparisons were adjusted in multi-level regression models. Results: 6238 adult trauma patients were admitted during the 15 month study period, of which 577 (9.2%) met inclusion criteria. They represented the most severely injured patients (ISS = 24 and mortality = 26%). There were 97 patients who received PHT and 480 in the non PHT control group. 244 units of RBCs and 698 units of plasma were placed on the helicopters, with 1.9% wastage. PHT was associated with reduced risks of 6-hour mortality (adjusted OR=0.08, 95% CI=0.01-0.87, p=0.04) and coagulopathy on arrival (TEG ACT ≥ 128, (adjusted OR=0.40, 95% CI=0.19-0.87, p=0.02) and a 13% non-significant improvement in hospital mortality. CONCLUSION: Prehospital plasma and RBC transfusion was associated with improved coagulation status and a reduction in the risk of death in the first 6 hours after admission, with negligible blood products wastage.
Abstract 14176: Preclinical Evaluation of the Engineered Stem Cell Chemokine Stromal Cell-Derived Factor 1- alpha in a Translational Ovine Myocardial Infarction Model.
Authors: John W. MacArthur, Jeffrey E. Cohen, Jeremy R. McGarvey, Yasuhiro Shudo, Jay B. Patel, Alexander S. Fairman, Alen Trubelja, Bryan B. Edwards, William Hiesinger, Andrew B. Goldstone, Pavan Atluri, James J. Pilla, Joseph H. Gorman, Robert C. Gorman, Y. Joseph Woo
Journal: Circulation (2013)

John MacArthur, 2013 Finalist and Presenting Author