tbuckley/cabot-search huggingface dataset:
Abstract 19585: Tidal Volume and Minute Ventilation Measurement at High, Low, and Erratic Respiratory Rates by a Non-Invasive Respiratory Monitoring System
Authors: Christopher Voscopoulos, Darren Fahy, Jordan Brayanov, Michael Lalli, Nicole Yocum, Jenny Freeman
Journal: Circulation (2012)

Introduction: Changes in minute ventilation (MV) &amp; tidal volume (TV) signal the beginning of respiratory compromise which often precedes cardiopulmonary arrest. Currently, respiratory monitoring in non-intubated patients lacks objective &amp; quantitative methodology for determining the adequacy of ventilation. A non-invasive, Respiratory Volume Measurement (RVM) system has been developed to measure MV, TV and respiratory rate (RR) continuously. Previous work has demonstrated clinically acceptable accuracy and precision of RVM monitoring across normal respiratory patterns and rates. Hypothesis: RVM monitoring accurately yields tidal volume &amp; minute ventilation across abnormal breathing rates, and erratic patterns. Methods: We studied 51 adult subjects (93 visits, 2252 tests) at low (4 - 6 bpm), normal (8 - 20 bpm), and high (30 - 40 bpm) respiratory rates and during erratic breathing. TV, RR and MV were measured simultaneously with an impedance-based RVM system (ExSpiron, Respiratory Motion, Inc., Waltham, MA) and a dry rolling seal spirometer (Morgan Scientific Inc., Haverhill, MA). Advanced data processing algorithms displayed a real time respiratory curve and calculated RVM measurements. Results: Throughout the range of 4 bpm to 40 bpm and during erratic breathing, RVM measurements are highly-correlated with spirometer measurements, with an average MV and TV correlation coefficient of 0.96, 95% CI 0.93 to 0.99 (Fig 1). Across all subjects, median correlation coefficients ranged from 0.91 to 0.99. Conclusions: High correlation (r = 0.96) between spirometric measurements and RVM signals concludes that the RVM system is capable of monitoring respiratory status during normal and erratic breathing, and at high and low breathing rates. As a passive, continuous, non-invasive system, RVM monitoring of non-intubated patients could provide earlier indications of respiratory decline potentially permitting interventions to prevent cardiopulmonary arrest.
Abstract 8684: Atrial Fibrillation is Associated with Higher Risk of Dementia and Post-Dementia Hospitalization Mortality in Individuals Without Stroke: The Atherosclerosis Risk in Communities (ARIC) Study
Authors: Lin Y Chen, Faye Lopez, Rebecca Gottesman, Rachel Huxley, Sunil K Agarwal, Laura Loehr, Thomas Mosley, Alvaro Alonso
Journal: Circulation (2011)

Background Atrial fibrillation (AF) is associated with higher risk of dementia in stroke patients. This association in patients without stroke is unclear. We sought to determine whether AF is associated with higher risk of dementia hospitalization and post-dementia hospitalization mortality in subjects without stroke in the ARIC cohort. Methods We included 15,264 subjects (age 45-64 yrs) enrolled in 1987-89, free of stroke before AF, free of stroke between AF and dementia hospitalization, and followed through 2007. AF events and dementia hospitalizations were identified from hospitalization discharge codes; AF was also identified from 4 exam ECGs. Stroke events were identified via annual phone calls, hospital record searching, and were physician-adjudicated. All-cause mortality was determined by cohort surveillance of the National Death Index and annual phone calls. We ran multivariable proportional-hazards models to assess associations between AF (time-varying exposure) and the outcomes: dementia hospitalization and post-dementia hospitalization mortality. Models were adjusted for age, sex, race, center, education, occupation, smoking, BMI, hypertension, diabetes, heart failure, and coronary heart disease. Results During follow-up (median 18.7 yrs), there were 1,496 AF cases, 572 dementia hospitalizations, and 320 post-dementia hospitalization deaths. The multivariable HR (95% CI) of dementia hospitalization associated with AF was 1.44 (1.09-1.92), p=0.01. At 15 years, 12.9% of participants with AF and 2.1% without AF were hospitalized with dementia (log-rank test, p&lt;0.0001) (Figure). The multivariable HR (95% CI) of post-dementia hospitalization mortality associated with AF was 1.68 (1.16-2.24), p=0.006. Conclusions In persons without stroke, AF is associated with higher risk of dementia hospitalization and post-dementia hospitalization mortality. AF may increase risk of dementia via mechanisms other than cardio-embolic stroke.
Abstract 19284: Clinical Determinants of Global and Regional Left Ventricular Systolic Function by Cardiac Magnetic Resonance Imaging: The Jackson Heart Study
Authors: Pelbreton C Balfour, Solomon K Musani, Renaldo Williams, Tandaw S Samdarshi, Jeffrey Carr, William G Hundley, Greg Terry, Herman A Taylor, Vasan S Ramachandran, Ervin Fox
Journal: Circulation (2012)

Introduction: Cardiac MRI (CMRI) provides high-resolution images, along with accurate and reproducible measurements of global and regional left ventricular (LV) systolic function (including LV ejection fraction, stroke volume, global and regional systolic strain). We examined the cross-sectional association of traditional cardiovascular (CV) risk factors with CMRI determined systolic function in a community-based cohort of African Americans (AAs). Methods: We evaluated 1,322 Jackson Heart Study participants (63% women, mean age 57 years) who had MRI exams performed at Examination 2. Measures of LV systolic function included ejection fraction, stroke volume, global strain (considered the mean peak systolic midwall Eularian strain -averaged for the base, mid-ventricle and apex in all segments) and regional strain (averaged for the mid-ventricle or apex only). Clinical covariates included age, sex, systolic and diastolic BP, BMI, fasting glucose (FG), diabetes status (DM), lipids, smoking, alcohol use, hypertension (HTN) medication, lipid lowering medication, education and income. Multiple stepwise linear regression analysis was used to model the association of clinical covariates (independent variables) with global and regional measures of LV systolic function. Results: Regression analysis demonstrated that LV ejection fraction was independently and positively associated with systolic BP (p= 0.0002) but inversely associated with male sex and FG (p &lt; 0.0001 and p = 0.011 respectively). Stroke volume was independently and positively associated with male sex, systolic BP, and BMI (p &lt; 0.001 for all) but inversely related to age, diastolic BP, and smoking (p= &lt;0.01 for all). More optimal (more negative) global and mid wall systolic strain were inversely associated with older age, male sex, BMI, and smoking (all p &lt;0.002). Lower (more optimal) apical strain was inversely associated with older age, male sex, HTN status, higher BMI, and smoking (p &lt;0.02 for all) but was positively associated with DM (p= 0.049). Conclusions: In our cross-sectional study of a large AA community-based cohort, we identified several modifiable CV risk factors (BP, BMI, FG, smoking) associated with global and regional measures of LV systolic function as assessed by CMRI.
Abstract 9236: Receptor Tyrosine Kinase Signaling Causes Cardiac Hypertrophy in Adult <i>Drosophila</i>
Authors: Lin Yu, Joseph P Daniels, Matthew J Wolf
Journal: Circulation (2011)

Abnormalities in receptor tyrosine kinase (RTK) signaling are associated with dilated cardiomyopathies and cardiac hypertrophy in humans and mouse models. We have developed strategies based on fruit fly genetics to identify genes that cause cardiac abnormalities in order to better understand suppressors of cardiomyopathic phenotypes. To characterize the role of RTK pathway in adult Drosophila heart function, we expressed dominant negative or constitutively active EGFR (DN-EGFR or EGFR Act ) specifically in the fly heart using tinC-Gal4 drivers. DN-EGFR flies had enlarged hearts and poor systolic function as assessed by optical coherence tomography. Interestingly, the cardiac-specific expression of EGFR Act resulted in significantly reduced eclosion rates and poor survival of adult escapers, which die within 48hrs. Moreover, EGFR Act adult escapers showed abnormal cardiomyocyte myofibrils, smaller heart lumens and significant increases in concentric wall thickness consistent with cardiac hypertrophy. The number of cardiac nuclei among hearts expressing EGFR Act was the same as controls, suggesting the effect was not due to proliferation. Since EGFR stimulation results in the activation of Ras and multiple downstream components including Raf-ERK, Ral-GDS and PI3K-AKT, we examined the effects of cardiac-specific expression of constitutively active Ras85D (Ras85D V12 ), gain of function Raf (Raf GOF ) and constitutively active PI3K (PI3K Act ). Ras85D V12 and Raf GOF , but not PI3K Act phenocopied the effects of EGFR Act resulting in abnormal cardiac myofibrils, smaller heart lumens and thicker concentric wall. To our knowledge, our findings represent the first evident of cardiac hypertrophy in the fruit flies. These results suggest that Ras-mediated activation of Raf-ERK may be a major contributor to the abnormal cardiac hypertrophy phenotype. Our ongoing studies are focused on the rescue of the Ras85D Act phenotype by ERK inhibition and the identification of gene transcripts that correlate with cardiac hypertrophy in adult Drosophila .
Abstract 18722: Cardiac Stimulation Occurs with Electronic Control Devices and is Dependent Upon Subject Size, Dart Location, and Device Characteristics
Authors: Greg C Flaker, Scott M Koerber, Sivakumar Ardhanari, Anand Chockalingam, Pawel Zymek, Wayne McDaniel
Journal: Circulation (2012)

Introduction Electronic control devices (ECDs) are weapons used to incapacitate violent subjects. Subjects have died suddenly after ECD application but since cardiac arrhythmias have been inconsistently observed during ECD application to animals, the cause for death is uncertain. We hypothesized that cardiac stimulation, if apparent during ECD application, could be detected by transesophageal echocardiography (TEE) and, if present, could be related to the model of ECD. Methods Four Yorkshire pigs were anesthetized, paralyzed with vecuronium, and restrained in a supine position. A GE 6T echo probe was placed in the esophagus to directly visualize left ventricular function. M-mode echocardiography was used to estimate heart rate. Two dart locations, chest and abdomen, were assessed. ECD energy application was delivered from one of 5 commercially available devices (Taser X26, Singer S200 AT, Taser M 26, Taser X-3, and Taser C2, all with different waveform characteristics) in random order to each pig, 4 times in each orientation. Results Cardiac stimulation, characterized by an abrupt increase in heart rate, reduction in myocardial contractility and mitral valve standstill, was detected with chest dart application in small pigs with all devices except the Taser X3 and in large pigs only with the S200 AT device (Table 1). Cardiac stimulation did not occur with abdominal dart application. VF was not observed. Conclusion Cardiac stimulation occurs during ECD application in pigs. Stimulation is dependent upon dart orientation and pig size. Refinement in waveform characteristics may result in ECD’s with a lower risk of cardiac stimulation. Table 1: Heart Rate Response During ECD Stimulation *P &lt; 0.0001 comparing cardiac heart rate with abdominal heart rate (Group 1)
Abstract 18787: Population-Based Data from Western Alaska Native People Show High Rates of CHD and Stroke Mortality: The WATCH Study
Authors: Jesse S Metzger, Kathleen R Koller, Scarlett Hopkins, E D Asay, Abigail W Wolfe, Cristiane Kaufmann, Melissa A Austin, Jason G Umans, Barbara V Howard, Bert B Boyer
Journal: Circulation (2012)

Background: Early low rates of CVD among Western Alaska native people were attributed to consumption of omega-3 rich foods. Mortality data suggest that rates are rising, but no population-based data have been reported. Methods: The Western Alaska Tribal Collaborative for Health (WATCH) combines three ongoing population-based studies - EARTH, CANHR, and GOCADAN, as well as data from the ASP. The consolidated cohort, the largest study of Western Alaska Native people, consists of 4,569 men and women &gt;18 yrs of age who underwent baseline exams between 2000 and 2010 and were followed an average of 6.7 years (&lt;1% lost to follow-up). CHD, stroke, and all CVD mortality were reviewed and adjudicated using standardized criteria. CHD deaths included MI, definite sudden death due to CHD, and definite fatal CHD. Stroke included those with evidence of rapid fatal onset of localized neurologic deficit or imaging consistent with stroke. CVD included CHD, stroke, and other fatal CVD. Age-adjusted rates (to the 2000 US census) were compared with those of US Whites and Blacks. Results: The baseline cohort was 54% female (mean age 40y for men and 42y for women) (Table). After an average 6.7 years, there were a total of 48 CVD deaths, 30 from CHD, and 17 from stroke. In Western Alaska native people, CHD mortality was similar to that of US Whites, with mortality in men exceeding that in women, but somewhat lower than rates for US Blacks; stroke mortality was similar in men and women, exceeding rates in both US Whites and Blacks. Conclusions: These results demonstrate high rates of CVD mortality, especially for stroke, compared with US Whites and Blacks, suggesting increasing rates in Western Alaska native people. Longer follow up to increase sample sizes is needed to confirm this trend, and the role of risk factors in these changes needs investigation. However, even these limited data suggest that community-based CVD prevention is needed in these populations.
Abstract 18772: Combined Therapeutic Effect of Probucol and Cilostazol on Endothelial Function in Patients with Silent Cerebral Lacunar Infarcts and Hypercholesterolemia
Authors: Bonpei Takase, Yuko Higashimura
Journal: Circulation (2012)

Flow-mediated dilation (FMD) and nitroglycerin-induced dilation (NMD) in brachial artery is excellent modality for evaluating endothelial function (ECF), and silent lacunar cerebral infarcts (SLCI) detected by MRI complicated with hyperlcholesterolemia is associated with untoward prognosis for cardiovascular events through impaired ECF. To investigate if combined therapy of probucol and cilostazol can ameliorate ECF in SLCI with mild hyperlcholesterolemia (MH; LDL-c&gt; 100 mg/dL), we measured FMD and NMD by UNEXEF18G before and after 4-weeks combined treatment of probucol (500 mg/day) and cilostazol (200 mg/day) in 24 patients with SLCI and MH (72±7 years old) with impaired ECF (FMD&lt;6%). Patients were randomly allocated into two treatment arms such as aspirin (100 mg/day) with behavioral modification such as diet and/or exercise therapy (A-group, n=17) and probucol and cilostazol treatment (PC-group, n=17) with behavioral modification. Although baseline FMD were not different between two treatment arms (2.7±1.5 vs. 2.6±1.5%, NS), PC-group significantly improved FMD (from 2.6±1.5 to 3.5±1.7%, P&lt;0.05) whereas A-group had no effect on FMD (from 2.6±1.2 to 2.9±1.4%, NS).There were no different effects in NMD in two groups. Effects of treatments on lipid profiles were more profound in PC-group. Conclusions; Combined treatment of probucol and cilostazol can subacutely ameliorate ECF detected by FMD in SLCI with MH. This combination therapy possibly prevents further cardiovascular events through improving both ECF and lipid profiles.
Abstract 18700: Accelerated Endothelial Regeneration and Survival Attenuate Vein Graft Atherosclerosis via Terahydrobiopterin-Dependent eNOS Coupling
Authors: Ziad A Ali, Ruth Rinze, Charalambos Antoniades, Gillian Douglas, Yanhua Hu, Qingzhong Xiao, David Greaves, Nicholas Alp, Qingbo Xu, Keith Channon
Journal: Circulation (2012)

As a result of surgical trauma, ischemia and exposure to arterial pressure the majority of endothelium in vein grafts (VG) undergo necrosis or apoptosis. We hypothesized that increased eNOS coupling could protect endothelial viability after VG surgery. To investigate this we utilized a transgenic mouse with endothelial-targeted overexpression of the essential eNOS coupling cofactor BH4. We investigated the effect of BH4 on endothelial cell survival and vascular remodeling in vitro and in vivo using ApoE-KO mice with endothelial-targeted overexpression of the rate limiting enzyme of BH4 synthesis GTP cyclohydrolase 1 (GCH) and LacZ reporter gene. BH4 levels were increased 10-fold in primary endothelium and 5-fold in aorta from GCH/ApoE-KO mice compared with ApoE-KO, without concomitant increases in eNOS protein. Despite no differences at baseline, following 4 days of culture, total endothelial cell number, colony size and number from GCH/ApoE-KO mice were increased (5-fold P=0.05; 2-fold P=0.02; 2-fold P=0.06 respectively, n=6) as were putative EPC levels from bone-marrow mononuclear cells determined by culture (15%,P=0.04) and FACS (26%, P=0.03). Vascular injury as a result of VG surgery in ApoE-KO mice led to significant neointima that was augmented by 61% (P=0.002) in GCH/ApoE-KO mice. Furthermore, endothelial repopulation was accelerated by 21% (P=0.01) and endothelial survival 44% (P=0.03) in these animals. O2- production was significantly attenuated in GCH/ApoE-KO mice measured on both aortic sections using oxidative microtopography and whole aorta by lucigenin chemiluminescence. eNOS inhibition by L-NAME reversed these effects indicating that under basal conditions GCH/ApoE-KO mice had preserved eNOS coupling promoting NO synthesis. In keeping with these findings in 219 patients with coronary artery disease, analysis of saphenous vein and internal mammary artery identified that high vascular BH4 levels were associated with greater vasorelaxations to acetylcholine (P&lt;0.05) and reduced total L-NAME inhibitable O2- suggesting improved eNOS coupling. Availability of BH4 within the endothelium critically modulates the response to vascular injury by maintaining eNOS coupling and accelerating endothelial regeneration.
Abstract 18728: Plasma Heparin Cofactor II Activity is a Predictor of Diffuse Coronary Artery Narrowing in Patients with Diabetes Mellitus
Authors: Nobuyuki Takamori, Masashi Akaike, Ken-ichi Aihara
Journal: Circulation (2012)

Background: Heparin cofactor II (HCII) is a major physiological inhibitor of thrombin action. We previously reported high plasma HCII was protective against in-stent restenosis after coronary stenting and carotid atherosclerosis. Furthermore, we reported that HCII was a predictor of cardiovascular events in patients with coronary heart disease. Kataoka et al reported patients with DM had smaller coronary vessel and longer diseased segment than those with impaired glucose tolerance (IGT) and normal glucose tolerance. HCII and morphologic characteristics of diabetic coronary was unknown. Methods: We enrolled 20 diabetic patients examined by coronary angiography, sequentially (13 males and 7 females; age, 67.9+/-10.4yrs, HbA1c&gt;/=7.0%). Coronary cinearteriography was analyzed by quantitative coronary angiography (QCA) with Cardiovascular Measurement System (CCIP-310/W). Segment diameter&lt;1.5mm as diseased lesions were determined. And diseased lesion length and HCII activity were analyzed, statistically. Results: The mean plasma level of HCII activities was 101.4+/-18.6%. And the mean of diseased lesion length was 13.7+/-12.0mm. Multivariate analysis showed age, low-HDLemia, smoking habit and disease period of DM were positively correlated with ALL, and HCII activity was negatively correlated. Univariate analysis showed HCII activity was negatively correlated with ALL, and disease period of DM was positively. That is, HCII activity and disease period of DM were correlated with lesion length of coronary artery diffuse-narrowing in diabetic patients. . Conclusions: The results suggested that low level of plasma HCII activity was correlated with diffuse coronary artery narrowing in patients with diabetic mellitus.
Abstract 18794: Temporal Relationship Between Mitochondrial Membrane Potential (ΔΨm) Depolarization and Loss of Excitability in Globally Ischemic Rabbit Heart
Authors: Paul W Venable, Tyson G Taylor, Junko Shibayama, Mark Warren, Kenneth W Spitzer, Alexey V Zaitsev
Journal: Circulation (2012)

Mitochondrial membrane potential (ΔΨm) depolarization has been implicated in the loss of excitability during ischemia, which could be relevant for resuscitation after cardiac arrest. The timing and degree of ΔΨm loss during no-flow ischemia in whole hearts is still poorly documented, in part due to the difficulty of estimating ΔΨm dynamics under this condition. We use a new approach based on the spatially periodic pattern present in the fluorescence emitted by potentiometric fluorophore TMRM when the dye accumulates in well-polarized mitochondria. This periodicity creates a distinct “mitochondrial” peak (MP) in the spatial Fourier spectrum corresponding to the sarcomere length (∼2 μm). Redistribution of TMRM upon ΔΨm depolarization diminishes the area under MP (MPA). We used Langendorff-perfused rabbit hearts mechanically uncoupled with blebbistatin (5.7μM) and stained with TMRM (450 nM). Confocal images were obtained from posterior left ventricular epicardium. Mitochondrial uncoupler FCCP (5 μM) and glycolytic inhibitior iodoacetate (IA, 15 mM) were used to validate MPA method. Eight hearts underwent minimum 1 hour global-ischemia; 4 hearts remained in sinus rhythm, 4 hearts were paced at 6.67 Hz to simulate ventricular fibrillation. FCCP reduced MPA to 32+/-6% of baseline; subsequent application of IA made MPA undetectable. During global ischemia ΔΨm loss started after a variable delay, was gradual and was not different between paced and non-paced hearts. MPA decreased to 50% of baseline at 44±17 (from 10 to 64) minutes and to 32% of baseline at 49±16 (from 27 to 70) minutes of ischemia. The minimum MPA value was 7±9% (range, 0-26%) of baseline and was observed at 65±9 minutes of ischemia (range, 51-72 minutes). Complete loss of excitability occurred earlier in paced than in non-paced hearts (33.2±3.1 vs. 45.0±7.2 min, p&lt;0.05) but no clear relationship between ΔΨm dynamics and loss of excitability could be found. Conclusions: In this model a significant ΔΨm loss, comparable with severe metabolic inhibition, occurs only after prolonged time of global ischemia, is not accelerated by rapid pacing and is not correlated with the loss of excitability. This suggests a limited the role of ΔΨm dynamics in the outcomes of resuscitation after sudden cardiac arrest.