Cardiology Commons^™

Evaluation Of The Effect Of Milner-Fenwick Video-Based Education And Teach-Back On Knowledge Acquisition In Atrial Fibrillation Patients, Melissa Czarapata

DNP Projects

PURPOSE: The purpose of this study was to evaluate if video education impacts knowledge acquisition and health literacy in patients with atrial fibrillation. METHODS: This study employed a descriptive, pretest-posttest single site comparative design. Baseline health literacy was assessed before video education was completed using the Atrial Fibrillation Knowledge scale. Health literacy regarding atrial fibrillation was again assessed for the same participants immediately after video education was completed and again in 7 to 10 days through the use of the Atrial Fibrillation Knowledge scale and teach-back questions. RESULTS: There was no statistical significance found when comparing scores before and after …

Stroke Outcomes With Vorapaxar Versus Placebo In Patients With Acute Coronary Syndromes: Insights From The Tracer Trial, Leo Ungar, Robert M. Clare, Fatima Rodriguez, Bradley J Kolls, Paul W. Armstrong, Philip Aylward, Claes Held, David J. Moliterno, John Strony, Frans Van De Werf, Lars Wallentin, Harvey D. White, Pierluigi Tricoci, Robert A. Harrington, Kenneth W. Mahaffey, Chiara Melloni

Gill Heart & Vascular Institute Faculty Publications

Background—Vorapaxar, a protease‐activated receptor‐1 antagonist, is approved for secondary prevention of cardiovascular events but is associated with increased intracranial hemorrhage.

Methods and Results—TRACER (Thrombin Receptor Antagonist for Clinical Event Reduction in Acute Coronary Syndrome) was a trial of vorapaxar versus placebo among patients with acute coronary syndrome. Strokes were adjudicated by a central events committee. Of 12 944 patients, 199 (1.5%) had ≥1 stroke during the study period (median follow‐up, 477 days). Four patients had a single stroke of unknown type; 195 patients had ≥1 stroke classified as hemorrhagic or nonhemorrhagic (165 nonhemorrhagic, 28 hemorrhagic, and 2 both). …

Clopidogrel Versus Newer P2y12 Antagonists For Percutaneous Coronary Intervention In Patients With Out-Of-Hospital Cardiac Arrest Managed With Therapeutic Hypothermia: A Meta-Analysis, Ayman Elbadawi, Islam Y. Elgendy, Ahmed H. Mohamed, Kirolos Barssoum, Erfan Alotaki, Gbolahan O. Ogunbayo, Khaled M. Ziada

Internal Medicine Faculty Publications

Introduction: The impact of therapeutic hypothermia (TH) on outcomes of percutaneous coronary intervention (PCI) and the optimal antiplatelet treatment remains debatable.

Methods: Electronic databases were searched for randomized trials and observational studies to evaluate the available clinical evidence comparing the use of clopidogrel versus newer P2Y12 antagonists in cases of TH after PCI. The primary outcome was in-hospital definite stent thrombosis while the secondary outcomes were in-hospital mortality and major bleeding. Fixed-effects risk ratios (RRs) were estimated using Mantel–Haenszel method.

Results: The final analysis included five studies with a total of 290 patients. There was no difference in the incidence …

Macrophage-Derived Netrin-1 Promotes Abdominal Aortic Aneurysm Formation By Activating Mmp3 In Vascular Smooth Muscle Cells, Tarik Hadi, Ludovic Boytard, Michele Silvestro, Dornazsadat Alebrahim, Samson Jacob, Jordyn Feinstein, Krista Barone, Wes Spiro, Susan Hutchison, Russell Simon, Debra L. Rateri, Florence Pinet, David Fenyo, Mark Adelman, Kathryn J. Moore, Holger K. Eltzschig, Alan Daugherty, Bhama Ramkhelawon

Physiology Faculty Publications

Abdominal aortic aneurysms (AAA) are characterized by extensive extracellular matrix (ECM) fragmentation and inflammation. However, the mechanisms by which these events are coupled thereby fueling focal vascular damage are undefined. Here we report through single-cell RNA-sequencing of diseased aorta that the neuronal guidance cue netrin-1 can act at the interface of macrophage-driven injury and ECM degradation. Netrin-1 expression peaks in human and murine aneurysmal macrophages. Targeted deletion of netrin-1 in macrophages protects mice from developing AAA. Through its receptor neogenin-1, netrin-1 induces a robust intracellular calcium flux necessary for the transcriptional regulation and persistent catalytic activation of matrix metalloproteinase-3 (MMP3) …

Platelet Cd36 Signaling Through Erk5 Promotes Caspase-Dependent Procoagulant Activity And Fibrin Deposition In Vivo, Moua Yang, Andaleb Kholmukhamedov, Marie L. Schulte, Brian C. Cooley, Na'il O. Scoggins, Jeremy P. Wood, Scott J. Cameron, Craig N. Morrell, Shawn M. Jobe, Roy L. Silverstein

Saha Cardiovascular Research Center Faculty Publications

Dyslipidemia is a risk factor for clinically significant thrombotic events. In this condition, scavenger receptor CD36 potentiates platelet reactivity through recognition of circulating oxidized lipids. CD36 promotes thrombosis by activating redox-sensitive signaling molecules, such as the MAPK extracellular signal-regulated kinase 5 (ERK5). However, the events downstream of platelet ERK5 are not clear. In this study, we report that oxidized low-density lipoprotein (oxLDL) promotes exposure of procoagulant phosphatidylserine (PSer) on platelet surfaces. Studies using pharmacologic inhibitors indicate that oxLDL-CD36 interaction–induced PSer exposure requires apoptotic caspases in addition to the downstream CD36-signaling molecules Src kinases, hydrogen peroxide, and ERK5. Caspases promote PSer …

Restoration Of Left Ventricular Function Following Lvad Implantation – Remission Or Recovery? A Case Series., Shiksha Joshi, Mariah Barlow, Maya Guglin

The VAD Journal

Background

A wide range of left ventricular (LV) recovery rates on left ventricular assist device (LVAD) support have been reported. In this case series, we summarize our experience with LVAD explantation for presumed LV recovery.

Case series

Out of 240 patients who received an LVAD implant in our program since its inception, we explanted/inactivated the pump for presumed LV recovery in only three patients. All three of these patients had relapse of cardiomyopathy within 6 months of explantation.

Conclusion

Our experience does not support the existence of LV recovery following LVAD implantation as a common phenomenon. Improvement in LV function …

Examining Symptom Trajectories That Predict Worse Outcomes In Post-Cabg Patients, Ming-Fen Tsai, Shiow-Luan Tsay, Debra K. Moser, Tsuey-Yuan Huang, Feng-Chun Tsai

Nursing Faculty Publications

Background: Coronary artery bypass grafting is one of the most common interventional revascularisation procedures used to treat coronary artery disease worldwide. With a wide variability in postoperative cardiac symptoms, identification of symptom trajectories during the 3-month postoperative recovery period may improve clinicians’ abilities to support symptom recovery.

Aims: To identify distinct trajectories of cardiac symptoms seen over time in a cohort of patients during the 3-month post-coronary artery bypass grafting period, and determine clinical characteristics associated with different symptom trajectories postoperatively.

Methods: A prospective trial used the cardiac symptom survey to determine patient symptoms at baseline prior to surgery, and …

Trajectory Of Thirst Intensity And Distress From Admission To 4-Week Follow Up At Home In Patients With Heart Failure, Nana Waldréus, Misook L. Chung, Martje H. L. Van Der Wal, Tiny Jaarsma

Nursing Faculty Publications

Background: Patients with heart failure (HF) can suffer from increased thirst intensity and distress. Trajectories of thirst intensity and distress from hospital to home are unclear. The aim of this study was to describe thirst intensity and distress trajectories in patients from the time of hospital admission to 4 weeks after discharge, and describe trajectories of thirst intensity and distress by patients’ characteristics (gender, age, body mass index [BMI], plasma urea, anxiety, and depression).

Patients and methods: In this observational study, data were collected from patients with HF (n=30) at hospital admission, discharge, and at 2 and 4 weeks after …

Wearable Cardioverter-Defibrillator After Myocardial Infarction, Jeffrey E. Olgin, Mark J. Pletcher, Eric Vittinghoff, Jerzy Wranicz, Rajesh Malik, Daniel P. Morin, Steven Zweibel, Alfred E. Buxton, Claude S. Elayi, Eugene H. Chung, Eric Rashba, Martin Borggrefe, Trisha F Hue, Carol Maguire, Feng Lin, Joel A. Simon, Stephen Hulley, Byron K. Lee, Vest Investigators

Gill Heart & Vascular Institute Faculty Publications

BACKGROUND

Despite the high rate of sudden death after myocardial infarction among patients with a low ejection fraction, implantable cardioverter–defibrillators are contraindicated until 40 to 90 days after myocardial infarction. Whether a wearable cardioverter–defibrillator would reduce the incidence of sudden death during this high-risk period is unclear.

METHODS

We randomly assigned (in a 2:1 ratio) patients with acute myocardial infarction and an ejection fraction of 35% or less to receive a wearable cardioverter–defibrillator plus guideline-directed therapy (the device group) or to receive only guideline-directed therapy (the control group). The primary outcome was the composite of sudden death or death from …

Comparison Of Left Ventricular Strains And Torsion Derived From Feature Tracking And Dense Cmr, Gregory J. Wehner, Linyuan Jing, Christopher M. Haggerty, Jonathan D. Suever, Jing Chen, Sean M. Hamlet, Jared A. Feindt, Walter Dimitri Mojsejenko, Mark A. Fogel, Brandon K. Fornwalt

Biomedical Engineering Faculty Publications

Background: Cardiovascular magnetic resonance (CMR) feature tracking is increasingly used to quantify cardiac mechanics from cine CMR imaging, although validation against reference standard techniques has been limited. Furthermore, studies have suggested that commonly-derived metrics, such as peak global strain (reported in 63% of feature tracking studies), can be quantified using contours from just two frames – end-diastole (ED) and end-systole (ES) – without requiring tracking software. We hypothesized that mechanics derived from feature tracking would not agree with those derived from a reference standard (displacement-encoding with stimulated echoes (DENSE) imaging), and that peak strain from feature tracking would agree with …

Effects Of Beta Blockers And Ace Inhibitors After Left Ventricular Assist Device Implantation, Gaurang Vaidya, Emma Birks, Jessica Pillarella, Benjamin Salgado, Rajakrishnan Vijayakrishnan, Andrew Lenneman, Mark Slaughter, Dmitry Abramov

The VAD Journal

Purpose: While Beta blockers(BB) and Angiotensin system blockers(ACEinh/ARB) are important components in advanced heart failure therapy, their use after left ventricular assist device (LVAD) implantation remains controversial. Concern has been raised about possible adverse effects of BB on right ventricular(RV) function while tolerance and efficacy/outcome data for ACEinh are lacking. This study aimed to characterize the use of medical therapy post-LVAD implantation and to evaluate its safety and efficacy. Methods: Demographic, clinical and echocardiographic variables of patients implanted with a continuous-flow LVAD between 2012 and 2015 at a single center were retrospectively reviewed. Mortality and heart failure(CHF) hospitalizations were followed …

Electrocardiographic Characteristics, Antiarrhythmic Utilization, And Outcomes In Patients With Left Ventricular Assist Devices, Scott Lundgren, Elizabeth Lyden, Douglas Stoller, Marshall Hyden, Adam Burdorf, Ronald Zolty, John Um, Brian Lowes

The VAD Journal

Background: Left ventricular assist devices (LVAD) are an increasingly used therapy for patients with advanced heart failure. Arrhythmias are common complications following LVAD implantation requiring admission, initiation, and escalation of medical therapy. Despite their frequent use in the treatment of arrhythmias, little has been reported regarding electrocardiographic changes, antiarrhythmic utilization, and outcomes post-LVAD.

Methods: A total of 309 patients who received a LVAD underwent retrospective chart review pre- and post-LVAD. Kaplan-Meier curves were calculated and compared using the log-rank test. Cox regression model was used for univariate analysis and those with a p

Results: There was a significant reduction in …

Safety And Efficacy Of Routine Bridging Anticoagulation For Subtherapeutic Anticoagulation In Outpatients With A Left Ventricular Assist Device, David C. Shisler, Gaurang N. Vaidya, Lori Muncy, Rajakrishnan Vijayakrishnan, Mark S. Slaughter, Emma J. Birks, Dmitry Abramov

The VAD Journal

Background

Anticoagulation with vitamin K antagonists is vital to prevent pump thrombosis in patients with left ventricular assist devices (LVADs). However, the safety and efficacy of bridging anticoagulation for the routine management of subtherapeutic international normalized ratio (INR) in stable outpatients remains poorly characterized.

Methods

In this retrospective study, a total of 60 LVAD outpatients had 110 episodes of subtherapeutic INR noted on routine testing. 34 of these episodes were managed with parenteral bridging anticoagulation and 76 were managed with only an adjusted dose of warfarin. The rates of bleeding and thromboembolic adverse events following these episodes of subtherapeutic INR …

Ticagrelor Reduces Thromboinflammatory Markers In Patients With Pneumonia, Travis R. Sexton, Guoying Zhang, Tracy E. Macaulay, Leigh Ann Callahan, Richard Charnigo, Olga A. Vsevolozhskaya, Zhenyu Li, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Despite treatment advances for sepsis and pneumonia, significant improvements in outcome have not been realized. Antiplatelet therapy may improve outcome in pneumonia and sepsis. In this study, the authors show that ticagrelor reduced leukocytes with attached platelets as well as the inflammatory biomarker interleukin (IL)-6. Pneumonia patients receiving ticagrelor required less supplemental oxygen and lung function tests trended toward improvement. Disruption of the P2Y₁₂ receptor in a murine model protected against inflammatory response, lung permeability, and mortality. Results indicate a mechanistic link between platelets, leukocytes, and lung injury in settings of pneumonia and sepsis, and suggest possible therapeutic approaches …

Azithromycin Therapy Reduces Cardiac Inflammation And Mitigates Adverse Cardiac Remodeling After Myocardial Infarction: Potential Therapeutic Targets In Ischemic Heart Disease, Ahmed Al-Darraji, Dalia Haydar, Lakshman Chelvarajan, Himi Tripathi, Bryana R. Levitan, Erhe Gao, Vincent J. Venditto, John C. Gensel, David James Feola, Ahmed Abdel-Latif

Gill Heart & Vascular Institute Faculty Publications

Introduction

Acute myocardial infarction (MI) is a primary cause of worldwide morbidity and mortality. Macrophages are fundamental components of post-MI inflammation. Pro-inflammatory macrophages can lead to adverse cardiac remodeling and heart failure while anti-inflammatory/reparative macrophages enhance tissue healing. Shifting the balance between pro-inflammatory and reparative macrophages post-MI is a novel therapeutic strategy. Azithromycin (AZM), a commonly used macrolide antibiotic, polarizes macrophages towards the anti-inflammatory phenotype, as shown in animal and human studies. We hypothesized that AZM modulates post-MI inflammation and improves cardiac recovery.

Methods and results

Male WT mice (C57BL/6, 6–8 weeks old) were treated with either oral AZM (160 …

Exploring The “Weekend Effect” On The Care Of Patients With Left Ventricular Assist Devices, Gbolahan O. Ogunbayo, Le Dung Ha, Naoki Misumida, Ayman Elbadawi, Qamar Ahmad, Remi Okwechime, Deborah Akanya, Andrew Kolodziej, Claude S. Elayi, Maya E. Guglin

The VAD Journal

Many studies have described differences in in-hospital outcomes and length of stay between patients treated for major cardiac conditions on weekdays versus weekends.¹ Our study aimed to explore the “weekend effect” on in-hospital care among patients with left ventricular assist devices.

Using data from the National Inpatient Sample (NIS) database, with a weighted estimate of more than 35 million admissions per year.² We identified patients 18 years or older with an ICD code signifying presence of a LVAD. Characteristics, comorbidities and clinical outcomes were compared between patients admitted on a weekend versus patients admitted on a weekday. The …

Reversal Of Fixed Pulmonary Hypertension With Transcatheter Valve Replacement For Aortic Insufficiency On Ventricular Assist Device Support, Faraz S. Ahmad, Mark J. Ricciardi, Laura J. Davidson, Allen S. Anderson, Kambiz Ghafourian, Ike Okwuosa, Esther Vorovich, Jane E. Wilcox, Daniel D. Holloway, Duc T. Pham, Jonathan D. Rich

The VAD Journal

We present a 43-year-old woman with a nonischemic cardiomyopathy implanted with a ventricular assist device (VAD) as bridge to transplant due to severe, “fixed” pulmonary hypertension (PH). Within three months of VAD implant, her “fixed” PH had resolved entirely. Nearly two years later, still supported with a VAD because of severe HLA allosensitization, she developed dyspnea and “moderate” aortic insufficiency (AI) by standard criteria. Invasive hemodynamics revealed recurrence of severe PH in the setting of elevated left-sided filling pressures. We concluded the AI was indeed severe and the cause of her symptoms and recurrent PH. Despite her minimally calcified aortic …

Lipid Phosphate Phosphatase 3 Regulates Adipocyte Sphingolipid Synthesis, But Not Developmental Adipogenesis Or Diet-Induced Obesity In Mice, Lorenzo Frederico, Liping Yang, Jason Brandon, Manikandan Panchatcharam, Hongmei Ren, Paul Mueller, Manjula Sunkara, Diana Escalante-Alcalde, Andrew J. Morris, Susan S. Smyth

Gill Heart & Vascular Institute Faculty Publications

Dephosphorylation of phosphatidic acid (PA) is the penultimate step in triglyceride synthesis. Adipocytes express soluble intracellular PA-specific phosphatases (Lipins) and broader specificity membrane-associated lipid phosphate phosphatases (LPPs) that can also dephosphorylate PA. Inactivation of lipin1 causes lipodystrophy in mice due to defective developmental adipogenesis. Triglyceride synthesis is diminished but not ablated by inactivation of lipin1 in differentiated adipocytes implicating other PA phosphatases in this process. To investigate the possible role of LPPs in adipocyte lipid metabolism and signaling we made mice with adipocyte-targeted inactivation of LPP3 encoded by the Plpp3(Ppap2b) gene. Adipocyte LPP3 deficiency resulted in blunted …

N-Terminal Pro-B-Type Natriuretic Peptide And Microsize Myocardial Infarction Risk In The Reasons For Geographic And Racial Differences In Stroke Study, Madeline R. Sterling, Raegan W. Durant, Joanna Bryan, Emily B. Levitan, Todd M. Brown, Yulia Khodneva, Stephen P. Glasser, Joshua S. Richman, George Howard, Mary Cushman, Monika M. Safford

Internal Medicine Faculty Publications

Background: N-terminal pro B-type peptide (NT-proBNP) has been associated with risk of myocardial infarction (MI), but less is known about the relationship between NT-proBNP and very small non ST-elevation MI, also known as microsize MI. These events are now routinely detectable with modern troponin assays and are emerging as a large proportion of all MI. Here, we sought to compare the association of NT-proBNP with risk of incident typical MI and microsize MI in the REasons for Geographic and Racial Differences in Stroke (REGARDS) Study.

Methods: The REGARDS Study is a national cohort of 30,239 US community-dwelling black and white …

Delayed Sternal Closure Does Not Reduce Complications Associated With Coagulopathy And Right Ventricular Failure After Left Ventricular Assist Device Implantation, Roh Yanagida, Navin Rajagopalan, Daniel L. Davenport, Thomas A. Tribble, Mark A. Bradley, Charles W. Hoopes

Internal Medicine Faculty Publications

Delayed sternal closure (DSC) is occasionally adopted after implantation of left ventricular assist device (LVAD). Recent studies suggest that DSC be used for high risk group of patients with coagulopathy, hemodynamic instability or right ventricular failure. However, whether DSC is efficacious for bleeding complication or right ventricular failure is not known. This study is single center analysis of 52 patients, who underwent LVAD implantation. Of those 52 patients, 40 consecutive patients underwent DSC routinely. The sternum was left open with vacuum assist device after implantation of LVAD. Perioperative outcome of the patients who underwent routine DSC were compared with 12 …

Acute Pressor Response To Psychosocial Stress Is Dependent On Endothelium‐Derived Endothelin‐1, Brandon M. Fox, Bryan K. Becker, Analia S. Loria, Kelly A. Hyndman, Chunhua Jin, Hannah Clark, Robin Johns, Masashi Yanagisawa, David M. Pollock, Jennifer S. Pollock

Pharmacology and Nutritional Sciences Faculty Publications

Background

Acute psychosocial stress provokes increases in circulating endothelin‐1 (ET‐1) levels in humans and animal models. However, key questions about the physiological function and cellular source of stress‐induced ET‐1 remain unanswered. We hypothesized that endothelium‐derived ET‐1 contributes to the acute pressor response to stress via activation of the endothelin A receptor.

Methods and Results

Adult male vascular endothelium‐specific ET‐1 knockout mice and control mice that were homozygous for the floxed allele were exposed to acute psychosocial stress in the form of cage switch stress (CSS), with blood pressure measured by telemetry. An acute pressor response was elicited by CSS in …

Rad Gtpase Deletion Atenuates Post-Ischemic Cardiac Dysfunction And Remodeling, Janet R. Manning, Lakshman Chelvarajan, Bryana R. Levitan, Catherine Nicole Kaminski Withers, Prabhakara R. Nagareddy, Christopher M. Haggerty, Brandon K. Fornwalt, Erhe Gao, Himi Tripathi, Ahmed Abdel-Latif, Douglas A. Andres, Jonathan Satin

Physiology Faculty Publications

The protein Rad interacts with the L-type calcium channel complex to modulate trigger Ca²⁺ and hence to govern contractility. Reducing Rad levels increases cardiac output. Ablation of Rad also attenuated the inflammatory response following acute myocardial infarction. Future studies to target deletion of Rad in the heart could be conducted to establish a novel treatment paradigm whereby pathologically stressed hearts would be given safe, stable positive inotropic support without arrhythmias and without pathological structural remodeling. Future investigations will also focus on establishing inhibitors of Rad and testing the efficacy of Rad deletion in cardioprotection relative to the time of …

What Did We Learn About Vads In 2017?, Maya Guglin

The VAD Journal

No abstract provided.

Management Of Aortic Insufficiency In Patients With Left Ventricular Assist Device ̶ A Retrospective Analysis, Hartmuth B. Bittner

The VAD Journal

Background: Aortic insufficiency is increasingly recognized as a complication of left ventricular assist device (LVAD) support and may lead to clinical decompensation requiring correction. This article describes experiences in managing patients presenting with concomitant aortic insufficiency and with de novo aortic insufficiency following left ventricular assist device implantations.

Methods: All patients undergoing LVAD implantation between 2012 and 2014 were included in this retrospective analysis if aortic valve insufficiency was present on implantation or newly developed (de novo) after implantation. Moderate to severe aortic valve insufficiency was corrected at implantation.

Results: The data of 39 patients were included. At the time …

Approach To Unresponsive Patient With Lvad, Maya Guglin

The VAD Journal

No abstract provided.

Unresponsive Patient With Lvad: A Case Series, Ameer Z. Musa, Julia Akhtarekhavari

The VAD Journal

Mechanical circulatory support (MCS) for patients with advanced heart failure (HF) is becoming more commonplace as technology has progressed and reliability of these systems has improved. We report our experience with three patients with cardiopulmonary arrest in the hospital and propose a protocol for the prompt assessment and treatment of an unresponsive patient with a LVAD in place. We presented three cases of unresponsive patients on LVAD support with low flow or no flow through the LVAD. Although all three of them were alive after resuscitation, none survived to discharge. In all three cases, there were no flaws in LVAD …

Aggressive Diuresis And Severity-Adjusted Length Of Hospital Stay In Acute Congestive Heart Failure Patients, Muhammad U. Butt

Theses and Dissertations--Clinical Research Design

To see if aggressive diuresis in first twenty four hours is associated with a comparable number of total days in the hospital as compared to non-aggressive diuresis. In this retrospective cohort study, we compared the length of hospital stay of consecutive patients admitted in one year based on their diuresis during the first twenty-four hours of hospitalization: aggressive diuresis (group 1) i.e. > 2400mL versus non-aggressive diuresis (group 2) i.e. ≤ 2400mL urine output. Patients were excluded if in cardiogenic shock, had creatinine level above 3 mg/dL on admission, or on dialysis. A total of 194 patients were enrolled (29 in …

Serum Tumor Necrosis Factor-Alpha Associates With Myocardial Oxygen Demand And Exercise Tolerance In Postmenopausal Women, Stephen J. Carter, David R. Bryan, William H. Neumeier, Stephen P. Glasser, Gary R. Hunter

Internal Medicine Faculty Publications

The functional implications of serum tumor necrosis factor-alpha (TNF-α), a marker of oxidative stress, on hemodynamic parameters at rest and during physical exertion are unclear. The aims of this investigation were to examine the independent associations of TNF-α on myocardial oxygen demand at rest and during submaximal exercise, while also evaluating the association of TNF-α on exercise tolerance. Forty, postmenopausal women, provided blood samples and completed a modified-Balke protocol to measure maximal oxygen uptake (VO_2max). Large artery compliance was measured by pulse contour analyses while rate-pressure product (RPP), an index of myocardial oxygen demand, was measured at rest …

Role Of Sex Chromosomes In Sexual Dimorphism Of Angii-Induced Abdominal Aortic Aneurysms, Yasir Alsiraj

Theses and Dissertations--Pharmacology and Nutritional Sciences

Abdominal aortic aneurysms (AAAs), a permanent dilation in the abdominal region of the aorta, is a highly sexually dimorphic disease. AAAs prevalence is ranging from 4-10 fold higher in males than females. Defining the mechanistic basis for reduced (in females) or increased (in males) AAA formation and progression may uncover potential therapeutic targets. The majority of studies examining sexual dimorphism focus on the role of sex hormones. However, genes residing on sex chromosomes, in addition to sex hormones, may contribute to sexual dimorphism of AAAs. For example, the X chromosome contains about 5% of the whole genome, but the role …

Tfpiα Interacts With Fva And Fxa To Inhibit Prothrombinase During The Initiation Of Coagulation, Jeremy P. Wood, Helle H. Petersen, Bingke Yu, Xiaoai Wu, Ida Hilden, Alan E. Mast

Gill Heart & Vascular Institute Faculty Publications

Tissue factor pathway inhibitor α (TFPIα) inhibits prothrombinase, the thrombin-generating complex of factor Xa (FXa) and factor Va (FVa), during the initiation of coagulation. This inhibition requires binding of a conserved basic region within TFPIα to a conserved acidic region in FXa-activated and platelet-released FVa. In this study, the contribution of interactions between TFPIα and the FXa active site and FVa heavy chain to prothrombinase inhibition were examined to further define the inhibitory biochemistry. Removal of FXa active site binding by mutation or by deletion of the second Kunitz domain (K2) of TFPIα produced 17- or 34-fold weaker prothrombinase inhibition, …