tbuckley/cabot-search huggingface dataset:
Abstract 324: Mean Arterial Pressure Achieved During Therapeutic Hypothermia is Not Associated With Neurologically Intact Survival Following Cardiac Arrest
Authors: Ryan D Hollenbeck, Jeremy S Pollock, Jennifer L Giuseffi, Li Wang, Michael N Young, Frank E Harrell, John A McPherson
Journal: Circulation (2013)

Background: Therapeutic hypothermia (TH) improves outcomes following cardiac arrest. The optimum hemodynamic goals during TH are unknown. The purpose of this study was to determine if mean arterial pressure (MAP) achieved during TH is associated with neurologically intact survival following cardiac arrest. Methods: Retrospective analysis was performed on 188 consecutive comatose survivors of cardiac arrest treated with TH in the cardiovascular intensive care unit of an academic tertiary care hospital. Shock on admission was defined as a systolic blood pressure &lt;90 mmHg or the need for any vasopressor or mechanical support at the time of admission. The cardiovascular portion of the Sequential Organ Failure Assessment (SOFA) score was used to define the achieved MAP for each patient. Multivariable logistic regression was used to examine the effect of achieved MAP during TH on neurologically intact survival to hospital discharged, defined by Cerebral Performance Category. Results: Neurologically intact survival was observed in 73/188 (38.8%) patients at hospital discharge, and in 48/162 (29.6%) at a median follow up interval of 3 months. Patients in shock at the time of admission had lower baseline MAP at the initiation of TH (81 versus 87 mmHg; p=0.002), but had similar achieved MAP during TH (80.3 versus 83.7 mmHg; p=0.11). Shock on admission was associated with poor survival (18% versus 52%; p&lt;0.001). Vasopressor use was common (85% of patients) and was not associated with increased mortality. A multivariable analysis including age, time to return of spontaneous circulation, initial rhythm, baseline MAP, and achieved MAP did not demonstrate a relationship between MAP achieved during TH and outcome at hospital discharge (OR 1.28, 95% CI 0.40-4.06; p=0.870) or at follow up (OR 1.09, 95% CI 0.32-3.75; p=0.976). Conclusions: We did not demonstrate an association between MAP achieved during TH and neurologically intact survival. Shock at the time of admission was clearly associated with poor outcomes. These data do not support the use of vasopressors to artificially increase MAP in the absence of shock. There is an urgent need for prospective, randomized trials to further define hemodynamic goals during treatment with TH.
Abstract 9920: Evaluation of Global Circumferential Strain as Prognostic Marker After Administration of β-blockers for Dilated Cardiomyopathy
Authors: Hidekazu Tanaka, Yasuhide Mochizuki, Kensuke Matsumoto, Yoshiki Yamadori, Takuma Sawa, Yoshiki Motoji, Junichi Imanishi, Tatsuya Miyoshi, Yuko Fukuda, Kazuhiro Tatsumi, Tetsuari Onishi, Hiroya Kawai, Ken-ichi Hirata
Journal: Circulation (2013)

Background: The prognosis of dilated cardiomyopathy (DCM) has improved by the use of β-blockers, and the appearance of left ventricular (LV) reverse remodeling is generally thought to result in a favorable prognosis. Although there are many prognostic predictors, they are not sensitive in individual patients. It is recently reported that global circumferential strain (GCS) is a powerful predictor of cardiac events and appears to be a better parameter than LV global function in heart failure patients. Accordingly, the objective of our study was to test the hypothesis that GCS predicted LV reverse remodeling after administration of β-blockers in patients with DCM. Methods: Fifty patients with DCM with EF of 28±8% (all&lt;45%) were prospectively recruited. Either carvedilol or bisoprolol was titrated to a targeting dose depending on the tolerability of each patient. Echocardiography was performed at enrollment and 8±5 months after the maintenance dose of β-blockers. LV reverse remodeling was defined as the presence of an absolute increase in EF of at least 10%. GCS was determined as the peak global speckle-tracking circumferential strain from mid-LV short-axis view. Event-free survival was tracked over 30-month. Results: Among all indices, GCS&lt;-4.01% best predicted responders, with 100% sensitivity, 62% specificity, and an area under the curve of 0.796 (p= 0.0004). On multivariate Cox proportional-hazards analysis, GCS was the independent and the most powerful predictor of LV reverse remodeling (hazard ratio, 1.228; p=0.02). Furthermore, patients with GCS&lt;-4.01% experienced fewer cardiovascular events than those with GCS≥-4.01% (log-rank p=0.023). Conclusions: GCS predicted LV reverse remodeling after administration with β-blockers, and was also associated with long-term outcome in patients with DCM. GCS may reflect intrinsic LV myocardial function , and have clinical implications for better management of such patients.
Abstract 9857: Inhibition of Endoplasmic Reticulum Stress Prevents Cardiac Rupture and Attenuates Cardiac Remodeling by Alleviating Mitochondrial Apoptosis and Nlrp3 Inflammasome Activation
Authors: Tao Luo, Baihe Chen, Xianbao Wang, Nisha Wang, Yanping Wang, Chao Zhang
Journal: Circulation (2013)

Background: Endoplasmic reticulum (ER) stress is involved in myocardial ischemia, but its role and underlying mechanism in the pathogenesis of post-infarct cardiac rupture and remodeling remain unclear. It is known that mitochondrial apoptosis and NLRP3 inflammasome activation are associated with tissue necrosis and fibrosis, which are crucial for cardiac rupture and remodeling. Here we hypothesized that ER stress promotes cardiac rupture and remodeling by increasing mitochondrial apoptosis and NLRP3 inflammation activation. Methods and Results: Left coronary ligation was used to produce myocardial infarction (MI) in C57BL/6 mice. There was 37.5% cardiac rupture rate in the control group during the early phase of MI (2-7 days). The survivals underwent cardiac remodeling and formed ventricular aneurysm with impaired systolic and diastolic functions at the end of 4 weeks. The rupture rate was significantly decreased to 20% in the 4-PBA intraperitoneal injection group (20 mg/kg/day) and the heart functions were improved at the end of 4 weeks. Furthermore, the ventricular aneurysm and myocardial fibrosis were much smaller. Western blot showed that the ER stress markers, mitochondrial bax, caspase 3, NLRP3, TGFβ1 and Smad 2 in the heart tissues of control group were significantly increased after MI, in which mitochondrial bax and caspase 3 were increased markedly in the early phase of MI (3 days), while NLRP3, TGFβ1 and Smad 2 were increased obviously in the late phase of MI (3-28 days). 4-PBA decreased those protein levels in the early and late phases of MI respectively. Then ER stress was induced in neonatal rat’s cardiomyocytes and fibroblasts by 3% hypoxia stimulation for 3 days. Calcein plus CoCL 2 , flow cytometry for JC-1 and western blot for mitochondrial bax and caspase 3 indicated that 4-PBA (0.5 mM) pretreatment protects the cardiomyocytes against mitochondrial-dependent apoptosis induced by hypoxia. Meanwhile, western blot showed that the expression of NLRP3, TGFβ1 and Smad 2 in the fibroblasts were increased by hypoxia stimulation but decreased by 4-PBA. Conclusion: Inhibition of ER stress is a novel therapeutic strategy for preventing post-infarct cardiac rupture and attenuating cardiac remodeling.
Abstract 269: Tracheal Intubation During Pediatric CPR: A Videographic Assessment
Authors: Aaron Donoghue, Ting-Chang Hsieh, Natasha Hoyte, Sage Myers, Akira Nishisaki
Journal: Circulation (2013)

Background: Pediatric cardiopulmonary resuscitation (CPR) continues to emphasize the inclusion of ventilation along with chest compressions. Tracheal intubation (TI) provides the most stable and effective means of ventilation, but performing TI is frequently associated with interruptions in CPR. Published data describing success with TI during CPR and quantifying CPR interruptions during TI in children is lacking. Objectives: To describe the frequency, duration, and outcomes of TI attempts during CPR in children in a tertiary pediatric ED, and to describe the interruptions in CPR associated with TI performance. Methods: Resuscitations in a tertiary pediatric ED are videorecorded as part of a continuous quality improvement project. Pediatric patients receiving CPR under videorecorded conditions in whom TI was attempted were prospectively identified and eligible for inclusion. Patients whose airway management did not include laryngoscopy (e.g. fiberoptic, surgical) were excluded. Data on intubation attempts (first attempt success tube placement, laryngoscopy time) and chest compressions (interruptions, duration of pauses) were collected. Univariate analysis of first attempt success was made between TI attempts with and without interruption in compressions. Results: Between November 2011 and April 2013, 22 patients had tracheal intubation (TI) attempts performed during cardiac arrest; a total of 44 attempts at TI occurred during CPR. 18/44 (41%) TI attempts had an associated interruption in CPR; the median duration in CPR interruption was 20 seconds (range 7 - 48). TI was successful in 17/20 patients (85%). Overall first attempt success at TI was 7/20 (35%); a median of 2 attempts were made per patient. TI attempts without interruption in CPR were successful in 6/22 (27%) compared to 5/11 (45%) when CPR was paused (p &lt; 0.001). Median laryngoscopy time was 35 seconds (range 13-89). Conclusions: Among pediatric ED patients, TI during CPR results in frequent and prolonged interruptions in CPR. Successful TI is more common when CPR is paused. Future studies should examine the relationship between TI and outcomes in pediatric cardiac arrest patients.
Abstract 261: Correction for Body Displacement for Accurate Delivery of Chest Compressions: Accuracy of the Truecpr Device on a Soft Mattress
Authors: Stefanie G Beesems, Rudolph W Koster
Journal: Circulation (2013)

Objective: Accelerometer based chest compression feedback devices overestimate compression depth by not accounting for a soft surface below the victim. TrueCPR, a new real-time feedback device, provides visual feedback on compression depth, based on measured changes in magnetic field strength between a backpad and a chestpad. We determined accuracy of that method on a calibrated test bench and on a manikin on a soft surface. Methods: First, we used a calibrated, computerized drill press compressing a Laerdal Resusci Anne SkillReporter manikin on a firm surface to verify calibration of its compression depth measurement, and to measure accuracy of the TrueCPR device. Then, we compared measurements of two feedback devices (TrueCPR and a sternum-only accelerometer) on a standard inflatable hospital mattress. Thirty manual chest compressions were given with feedback of TrueCPR or the accelerometer, to achieve the recommended depth of 50-60 mm and compared with the compression depth measured by the manikin. Results: Compared to the drill press, the manikin measured compression depth with error &lt;1 mm for depths below 55 mm and with 1-2 mm underestimation above 55mm. TrueCPR showed a systematic underestimation of 3-4 mm on a hard surface. On the mattress, TrueCPR showed an underestimation of 2-4 mm, where the accelerometer showed an overestimation of 17-23 mm (figure). A compression depth in the recommended range was achieved with TrueCPR in 23 of 30 compressions and with the accelerometer in 2 of 30 compressions. Conclusion: TrueCPR measures depth independent of the stiffness of the surface upon which the CPR is being performed with a constant underestimation of &lt;4 mm. A sternum-only accelerometer substantially overestimates depth when performing CPR on a soft surface. Correction for body displacement on a soft surface is essential for accurate delivery of chest compressions within the recommended depth range.
Abstract 9958: Enabling of PGC-1 Alpha Signaling by Alpha-lipoic Acid Inhibits and Reverses Vascular Senescence
Authors: Shiqin Xiong, Gloria Salazar, Nikolay Patrushev, Farshad Forouzandeh, Lula Hilenski, R. W Alexander
Journal: Circulation (2013)

Vascular senescence has been implicated in atherosclerotic arterial disease clinically and in animals. Senescence induction conditions include telomere and mitochondrial dysfunction, DNA damage, and elevated oxidative stress. Alpha-lipoic acid (ALA) is a powerful natural antioxidant, implying a potential important role of ALA in senescence pathogenesis. We showed recently peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1 alpha) is a primary negative regulator of vascular senescence. We thus posited that ALA may inhibit vascular senescence via enabling PGC-1 alpha signaling networks. We generated a PGC-1 alpha and ApoE double knockout mouse model and show that mice with PGC-1 alpha deficiency develop a senescence phenotype (2.25 fold) that is associated with increased cellular general ROS levels (3 fold) and mitochondrial superoxide production (2 fold). We demonstrate that ALA (100 μM for in vitro, 10 mg/kg/d for in vivo experiments) upregulates expression of PGC-1 alpha and PGC-1 alpha-dependent downstream ROS defense molecules, including SIRT1, catalase, MnSOD, heme oxygenase 1 (HO-1), and its mitochondrial targets including NRF-1 and 2, and TFAM, while decreases expression of the senescence marker p53 in mice aortas and vascular smooth muscle cells (VSMC). The upregulation of the endogenous antioxidants and mitochondrial targets is prevented by PGC-1 alpha deficiency. Further, ALA (100 μM) is sufficient to inhibit and reverse VSMC senescence through a blockade of PGC-1 alpha acetylation, thus preventing the downregulation of SIRT1 and catalase triggered by angiotensin II (Ang II), a major hormonal inducer of vascular senescence. Moreover, ALA inhibits Ang II-induced cellular ROS and mitochondrial superoxide production, both of which are abolished in the absence of PGC-1 alpha. Our findings show that ALA is an important activator of PGC-1 alpha signaling pathways and unravel a previously unappreciated role for ALA in mitigating oxidative stress-dependent vascular senescence via PGC-1 alpha. These observations support the notion that enabling of PGC-1 alpha signaling network might be a promising strategy in the development of intervention for oxidative stress-dependent, age-related, chronic diseases.
Abstract 9687: Network Analysis Identifies MicroRNA-22 as a Key Regulator of Vascular Calcification
Authors: Samantha Torquato, Hae-Young Lee, Bradley A Maron, Katherine A Cottrill, Stephen Y Chan, Joseph Loscalzo, Jane A Leopold
Journal: Circulation (2013)

MicroRNAs (miR) have been shown to regulate expression of individual signaling molecules involved in vascular calcification. We hypothesized that downregulation of select miRs would modulate a calcification program in human coronary artery smooth muscle cells (SMC) to influence mineralization. To identify candidate miRs, we used a systems biology approach and incorporated 246 calcification-related genes into a network that revealed 3,013 interactions. A hypergeometric analysis found 9 miRNAs that regulate the network with &gt;90% probability. Cross-referencing results with a miR microarray identified miR22 as a key regulator of the calcification network. To confirm the in silico analysis, SMC were transfected with anti-miR22 to decrease miR22 expression, with pre-miR22 to force miR22 expression, or with scrambled controls. Transfection with anti-miR22 increased SMC Ca 2+ levels by 126% (p&lt;0.05), and calcification by Alizarin red staining, while transfection with pre-miR22 inhibited SMC calcification. To determine how pro-calcifying mediators decrease miR22 levels, we examined c-myc, which negatively regulates miR expression. Chromatin immunoprecipitation assay demonstrated that c-myc bound to the miR22 promoter; SMC transfection with c-myc siRNA abrograted this response and increased miR22 levels. Next, we examined expression of miR22 targets identified by the network. Transfection of SMC with anti-miR22 increased expression of cysteine-rich angiogenic protein 61 (CYR61) by 154% (p&lt;0.01), Smad4 by 68% (p&lt;0.04), and its downstream target Runx2 by 112% (p&lt;0.01). Upregulation of these proteins was inhibited by forced expression of miR22. In an ex vivo rat aorta calcification assay, transfection of vessels with anti-miR22 increased vascular CYR61 expression and calcification, while transfection with pre-miR22 inhibited calcification. In human coronary arteries, in situ hybridization revealed increased levels of miR22 in vessels with limited calcification as compared to heavily calcified vessels with significant atherosclerotic disease. These findings demonstrate that miR22 modulates expression of key calcification-related intermediaries. Therapies that target this signaling pathway may limit vascular calcification.
Abstract 315: Characterization of Out of Hospital Resuscitation Utilizing Blood Transfusion
Authors: Jorge Mena-Munoz, Udayan Srivastava, Christian Martin-Gill, Brian Suffoletto, Francis Guyette
Journal: Circulation (2013)

Introduction: While blood transfusion in the hospital setting has been extensively studied, little data exists on out of hospital administration of blood products. We aimed to characterize patients receiving out of hospital blood product transfusion in a critical care transport network that carries blood products. Methods: We performed a retrospective review of patients transported by a regional critical care transport service from 1/1/2003 to 6/30/2012 who received blood products during transport. This service carries two units of un-crossmatched Packed Red Blood Cells (pRBCs) on every transport. We describe prehospital factors (vital signs, mechanism of injury, volume and type of blood product transfused) associated with blood transfusion. We further categorized out of hospital transfusions of blood products into three groups based on the volume transfused (lt350 ml, 350-700ml, gt700ml). We compared in-hospital outcomes (mortality, volume and type of subsequent blood transfusion, and need for emergent surgery [lt24 hours]) among these three groups to ascertain the impact of prehospital blood product transfusion. Results: We reviewed 1441 transports in which blood products were transfused. Most transfusions were inter-facility transfers (92%, CI 91-93%) and for non-traumatic illness (75%, CI 73-77%). The most common reason for transport was upper gastrointestinal bleeding (20%, 18-22%). A vast majority, 80% (CI 78-82%), of patients required subsequent in-hospital blood transfusion. In hospital 30-day mortality was high, 22% (CI 20-25%), as was need for emergent surgery 27% (CI 25-29%). Mean length of stay was 10.6 days and mean ICU length of stay was 7.2 days. Among those receiving blood products, those transfused with &amp;gt700ml had higher heart rates (94 vs. 103, p=0.01), whole blood lactate levels (3.5 vs. 6.2, p&amp;lt0.01), and lower systolic blood pressure (108 vs.122, p&amp;lt0.01) Conclusions: In this sample, the majority of patients receiving blood during critical care transport are during inter-facility transports and for non-traumatic conditions. Gastrointestinal hemorrhage is the most common indication for transfusion and 30-day mortality in this cohort is high.
Less Invasive Heart Surgery: Will It Fail or Prevail?
Authors: W. Randolph Chitwood
Journal: Circulation (2013)

Dr. William W. L. Glenn was a cardiac pioneer surgeon and innovator. He practiced and taught during what many have called “The Golden Era of Cardiac Surgery”. During this time most of the inaugural cardiac operations were developed and were based on solid physiologic principles. Although many of them were effective, most were superseded by better techniques to treat the same malady. However, many of these “obsolete operations” became the springboard for the development of current catheter-based and less invasive operations, as well as implantable devices, that we use today. With rapidly advancing technology in our specialty many current operations seem to be in jeopardy of replacement by effective least invasive cardiac procedures. Yet, a majority of cardiac surgeons still considered minimally invasive cardiac surgery a fading fad and that the proven excellent results of traditional cardiac operations will prevail. Nevertheless, the expanding adoption of effective minimally invasive and catheter-based cardiac operations in Europe and the United States is a strong predictor of a sustained “disruptive change” in our specialty. To this end, the lecture will try to unravel the conundrum of: Less Invasive Heart Surgery: Will it fail or prevail?
Abstract 326: Temperature Distribution During Hypothermia Induction Depends on Cooling Method and Blood Flow
Authors: Joshua Lampe, George Bratinov, Theodore Weiland, Josiah D Garcia, Uday Illindala, Lance B Becker
Journal: Circulation (2013)

Introduction: Animal research suggests that intra-arrest therapeutic hypothermia, cooling before return of spontaneous circulation (ROSC), may be more protective than inducing hypothermia after ROSC. Reduced blood flow should slow cooling rates, because the amount of blood flow will determine the amount of convective heat transfer. We hypothesize that intra-arrest cooling will result in significant temperature heterogeneity. Methods: 18 temperatures (7 brain, 4 surface, 7 thoracic and abdominal) were monitored in 75 domestic swine (~30 Kg) during hypothermia induction. Cooling technologies included: Control, femoral vein (FV) cold saline infusion, FV ice slurry infusion, carotid (CA) cold saline infusion, CA ice slurry infusion, nasopharyngeal cooling, heat exchange catheter cooling, and blanket cooling. Animals were assigned to three blood flow groups: normal circulation, cardiac arrest treated with mechanical chest compressions (CC), and untreated cardiac arrest. CC and hypothermia induction were started after ten minutes of untreated arrest. CC were performed at a rate of 100 cpm and a depth of 1.25”. For all flow states, the experiments were terminated after 60 min of cooling. Results: 18 Temperatures and cooling rates have been aggregated from 24 experimental groups with six reported time epochs per experiment, resulting in a data set that contains more than 4500 values. Initial analysis indicates that reductions in blood flow led to reduced cooling rates. The highest cooling rate in the right hemisphere of the brain during FV saline induction was -7.83 [[Unable to Display Character: ]]C/hr for normal flow, -4.47 [[Unable to Display Character: ]]C/hr for CPR, and -1.04 [[Unable to Display Character: ]]C/hr during no flow. Compartmentalization of cooling was observed during intra-CPR and intra-arrest cooling. Conclusions: Thermokinetics during intra-arrest cooling, even with ongoing CPR, is significantly different than post ROSC thermokinetics. Temperature heterogeneity increases the challenge of patient temperature monitoring, particularly for over-cooling. These data raise questions about how to optimize intra-arrest cooling.