Circulatory and Respiratory Physiology Commons^™

The Complementary Roles Of Vamp-2, -3, And -7 In Platelet Secretion And Function, Smita Joshi, Kanakanagavalli Shravani Prakhya, Alexis N. Smith, Harry Chanzu, Ming Zhang, Sidney W. Whiteheart

Saha Cardiovascular Research Center Faculty Publications

Platelet secretion requires Soluble N-ethylmaleimide Sensitive Attachment Protein Receptors (SNAREs). Vesicle SNAREs/Vesicle-Associated Membrane Proteins (v-SNAREs/ VAMPs) on granules and t-SNAREs in plasma membranes mediate granule release. Platelet VAMP heterogeneity has complicated the assessment of how/if each is used and affects hemostasis. To address the importance of VAMP-7 (V7), we analyzed mice with global deletions of V3 and V7 together or platelet-specific deletions of V2, V3, and global deletion of V7. We measured the kinetics of cargo release, and its effects on three injury models to define the context-specific roles of these VAMPs. Loss of V7 minimally affected dense and α …

Best3-Mediated Mekk2/3 Activation: A Novel Therapeutic Target In Aortopathies, Tatiana Zyrianova, Benjamin Lopez, Kathlyn Zou, Charles Gu, Dayna Pham, Sriharsha Talapaneni, Christopher M. Waters, Riccardo Olcese, Andreas Schwingshackl

Saha Cardiovascular Research Center Faculty Publications

Influenza-A virus (IAV) infects yearly an estimated one billion people worldwide, resulting in 300,000–650,000 deaths. Preventive vaccination programs and antiviral medications represent the mainstay of therapy, but with unacceptably high morbidity and mortality rates, new targeted therapeutic approaches are urgently needed. Since inflammatory processes are commonly associated with measurable changes in the cell membrane potential (Em), we investigated whether Em hyperpolarization via TREK-1 (K2P 2.1) K þ channel activation can protect against influenza-A virus (IAV)-induced pneumonia. We infected mice with IAV, which after 5 days caused 10–15% weight loss and a decrease in spontaneous activity, representing a clinically relevant infection. …

Deep Learning, 3d Ultrastructural Analysis Reveals Quantitative Differences In Platelet And Organelle Packing In Covid-19/Sarscov2 Patient-Derived Platelets, Sagar S. Matharu, Cassidy S. Nordmann, Kurtis R. Ottman, Rahul Akkem, Douglas Palumbo, Denzel R. D. Cruz, Kenneth Campbell, Gail Sievert, Jamie L. Sturgill, James Zachary Porterfield, Smita Joshi, Hammodah Rawhi Hammodah Alfar, Chi Peng, Irina D. Pokrovskaya, Jeffrey A. Kamykowski, Jeremy P. Wood, Beth A. Garvy, Maria A. Aronova, Sidney W. Whiteheart, Richard D. Leapman, Brian Storrie

Saha Cardiovascular Research Center Faculty Publications

Platelets contribute to COVID-19 clinical manifestations, of which microclotting in the pulmonary vasculature has been a prominent symptom. To investigate the potential diagnostic contributions of overall platelet morphology and their α-granules and mitochondria to the understanding of platelet hyperactivation and micro-clotting, we undertook a 3D ultrastructural approach. Because differences might be small, we used the high-contrast, high-resolution technique of focused ion beam scanning EM (FIB-SEM) and employed deep learning computational methods to evaluate nearly 600 individual platelets and 30 000 included organelles within three healthy controls and three severely ill COVID-19 patients. Statistical analysis reveals that the α-granule/ mitochondrion-to-plateletvolume ratio …

Lrp1 Protects Against Excessive Superior Mesenteric Artery Remodeling By Modulating Angiotensin Ii–Mediated Signaling, Jackie M. Zhang, Dianaly T. Au, Hisashi Sawada, Michael K. Franklin, Jessica J. Moorleghen, Deborah A. Howatt, Pengjun Wang, Brittany O. Aicher, Brian Hampton, Mary Migliorini, Fenge Ni, Adam E. Mullick, Mashhood M. Wani, Areck A. Ucuzian, Hong S. Lu, Selen C. Muratoglu, Alan Daugherty, Dudley K. Strickland

Saha Cardiovascular Research Center Faculty Publications

Vascular smooth muscle cells (vSMCs) exert a critical role in sensing and maintaining vascular integrity. These cells abundantly express the low-density lipoprotein receptor–related protein 1 (LRP1), a large endocytic signaling receptor that recognizes numerous ligands, including apolipoprotein E–rich lipoproteins, proteases, and protease-inhibitor complexes. We observed the spontaneous formation of aneurysms in the superior mesenteric artery (SMA) of both male and female mice in which LRP1 was genetically deleted in vSMCs (smLRP1–/– mice). Quantitative proteomics revealed elevated abundance of several proteins in smLRP1–/– mice that are known to be induced by angiotensin II–mediated (AngII-mediated) signaling, suggesting that this pathway was dysregulated. …

Macrophage Angiotensin-Converting Enzyme Reduces Atherosclerosis By Increasing Peroxisome Proliferator-Activated Receptor Α And Fundamentally Changing Lipid Metabolism, Duoyao Cao, Zakir Khan, Xiaomo Li, Suguru Saito, Ellen A. Bernstein, Aaron R. Victor, Faizan Ahmed, Aoi O. Hoshi, Luciana C. Veiras, Tomohiro Shibata, Mingtian Che, Lei Cai, Michifumi Yamashita, Ryan E. Temel, Jorge F. Giani, Daniel J. Luthringer, Ajit S. Divakaruni, Derick Okwan-Duodu, Kenneth E. Bernstein

Saha Cardiovascular Research Center Faculty Publications

Aims The metabolic failure of macrophages to adequately process lipid is central to the aetiology of atherosclerosis. Here, we examine the role of macrophage angiotensin-converting enzyme (ACE) in a mouse model of PCSK9-induced atherosclerosis.

Methods and results Atherosclerosis in mice was induced with AAV-PCSK9 and a high-fat diet. Animals with increased macrophage ACE (ACE 10/10 mice) have a marked reduction in atherosclerosis vs. WT mice. Macrophages from both the aorta and peritoneum of ACE 10/10 express increased PPARα and have a profoundly altered phenotype to process lipids characterized by higher levels of the surface scavenger receptor CD36, increased uptake of …

Contribution Of Metabolic Cell Swelling On Microcirculatory Perfusion In Septic Shock, Charles E. Payne

Theses and Dissertations

Sepsis, a systemic immunological response that leads to organ-dysfunction, the development of septic shock, and death has mortality rate of 15-25%. A subset of sepsis, septic shock, has an in-hospital mortality rate of 30-50%. Sepsis and its treatment are the most expensive healthcare problem in the United States with the US Agency for Healthcare Research and Quality estimating annual costs over $20 billion. Hypoxia experienced in septic shock induces metabolic cell and tissue swelling leading to further microcirculatory dysfunction and poor tissue perfusion. Reversing metabolic cell swelling corrects these perfusion defects. Two models were used in rats to induce septic …

Influence Of Maternal Nano-Titanium Dioxide Inhalation Exposure On Cyclooxygenase Metabolites: Maternal Microvascular And Sexually Dimorphic Feto-Placental Outcomes., Julie Anne Griffith

Graduate Theses, Dissertations, and Problem Reports (ETD)

Nano-titanium dioxide (nano-TiO₂) is an engineered nanomaterial (ENM), which is widely utilized in diverse products like surface coatings, cosmetics, medical devices, and filters. Inhaled nano-TiO₂ has been demonstrated to induce pulmonary inflammation, impair microvascular function, and hinder generational reproductive endpoints. These outcomes indicate why it is important to explore gestation, as it requires timely vascular adaptations to support maternal and fetal health and development. Therefore, the central hypothesis of my dissertation is: maternal nano-TiO₂ inhalation exposure will impact maternal microvascular function and fetoplacental hemodynamics and function in a sexually dimorphic manner.

The first purpose of …

Use Of Cardiomems Hf Sensor In Management Of Nyha Class Iii Heart Failure, Trevor Andrunik, Anne Eady

Physician Assistant Capstones, 2020-current

Objective: Assess the ability of continuous pulmonary artery pressure monitoring via implantable CardioMEMs HF device to reduce hospitalization in New York Heart Association (NYHA) Class III heart failure patients over the age of 18. Design: Systematic literature review. Methods: Searches were conducted via PubMed and ClinicalTrials.gov using the single search term “CardioMEMs.” Inclusion criteria narrowed results to studies performed in the last 10 years, randomized control trials, cohort studies, and utilizing heart failure related hospitalization as the primary endpoint. Results: The current data unanimously asserts that the CardioMEMs HF device is effective at reducing heart failure related hospitalizations, with secondary …

Patient Care Management Of Hypertension Through Improving Follow-Up And Reducing Missed Appointments In A Primary Care Clinic: A Qi Project, Victoria Idubor

Doctor of Nursing Practice

Background. Missed follow-up appointments constitute significant problems clinics and health centers face nationwide. A significant portion of primary care providers’ patients will require follow-up appointments to manage their chronic illnesses. About 20 to 40% of patients seen at this clinic have a history of hypertension. Uncontrolled hypertension has been shown to increase the risk of certain cardiovascular disease events and mortality. Follow-up appointments are crucial for patients with hypertension to monitor for more life-threatening signs and manage their overall care. Purpose. The purpose of this project is to improve the timely management of care for patients with hypertension …

Upper Gastrointestinal Bleeding During The Covid-19 Pandemic; Particularities Of Diagnosis And Therapy, Adrian Silaghi, Bogdan Severus Gaspar, Dragos Epistatu, Daniela Gabriela Bălan, Ioana Păunică, Anca Silvia Dumitriu, Stana Paunica, Bogdan Socea, Vlad Denis Constantin

Journal of Mind and Medical Sciences

SARS-COV 2 recently caused a global pandemic, with the first case being reported in Romania in February 2020. Important restrictive measures were imposed, so that the addressability of patients to medical services decreased. Upper gastrointestinal bleeding had more severe forms of evolution at the time of presentation, which required additional methods of diagnosis and treatment. This is a retrospective study performed on 268 patients, which aims to evaluate the type and effectiveness of different treatment methods for upper gastrointestinal bleeding during the COVID 19 pandemic. Severity assessment was performed by measuring the Rockall score and additional methods of diagnosis. The …

Fear Of Covid-19, Anxiety, Depression And Suicide Among Elderly Patients With Chronic Physical Or Mental Diseases, Vasiliki Holeva, Vasiliki Aliki Nikopoulou, Eleni Parlapani, Konstantinos Karkaletsis, Styliani Kokkoni, Dimitrios Nouvakis, Patroklos Theocharis, Ioannis Diakogiannis

Journal of Mind and Medical Sciences

Older age renders individuals vulnerable during public emergency crises. Considering that older adults are a highly heterogeneous and continuously growing demographic subgroup, this study aimed to assess the mental health impact of COVID-19 on two groups of older patients: a group of chronic physical disease and a group of chronic mental disease. A total of 102 patients completed the Fear of COVID-19 Scale, the Generalized Anxiety Disorder scale, the Brief Patient Health Questionnaire (PHQ-9) and several questions regarding demographic characteristics. Suicidality was assessed by the 9th item of the PHQ-9. According to the results, older chronic disease patients showed higher …

Healthy Exosomes And Their Effects On Diabetic Cardiomyocytes, Miguel A. Garza, Genaro A. Ramírez-Correa, Maria Lourdes Garza-Rodríguez, Andres J. Medina

MEDI 9331 Scholarly Activities Clinical Years

Extracellular Vesicles, and more specifically, exosomes, are essential for effective cell-to-cell communication in a wide variety of tissues. In the last couple of decades, these nanovesicles have been proven to be active participants and regulators in many disease processes; therefore, their therapeutic effects have been widely studied and proven in various cardiovascular diseases both, in vitro and in vivo. Thus, this study aims at assessing the effects of running healthy mice exosomes on cardiomyocyte and cardiac tissue samples obtained from diabetic mice. Here, we successfully extract exosomes from mice plasma and detect their presence through the use of anti-CD9 and …

Heart To Heart, Mom To Mom, Karis L. Tekwani

Journal of Patient-Centered Research and Reviews

This essay describes the human connection forged between two young moms, one the physician and one the patient, when their paths collided one night in the emergency department of a busy hospital. It describes a challenging and most memorable care experience in the career of a young emergency physician, the clinical outcome, and the patient’s appreciative follow-up message years later.

Pathophysiology Of Aortic Stenosis, Melissa Lee

Nursing Student Class Projects (Formerly MSN)

Pathophysiology of Aortic Stenosis

Melissa J. Lee

Department of Nursing, Otterbein University

NURS 6810: Advanced Pathophysiology for the Advanced Practice Nurse

Dr. Deana Batross & Dr. Shivani Bhatnagar

July 29, 2022

Pathophysiology of Aortic Stenosis

Proper evaluation of co-morbidities is imperative for patient safety and successful outcomes for patients undergoing anesthesia. Aortic stenosis (AS) is one of the most complex diseases encountered in anesthesia, affecting five percent of older adults and ten percent of the 80-89-year-old-cohort (Joseph et al., 2017). The pathophysiological development of AS is the end result of an inflammatory process caused by endothelial damage from mechanical stress, …

Cardiovascular Disease Awareness Program On Risk Factors For Cardiovascular Disease Among Adolescents In Selected Schools, In New Delhi, Komal Kumari

Manipal Journal of Nursing and Health Sciences

Introduction: Cardiovascular disease (CVD) is the main cause of mortality worldwide. The main risk factors include tobacco chewing/smoking, higher blood cholesterol, high blood pressure, physical inactivity, obesity, excessive alcohol use, age, sex, and heredity. Although CVDs commonly develop in middle age or later, risk factors are highly impacted by childhood practices that are continued into maturity. Knowledge gaps on CVD and its risk factors are major obstacles to effective prevention and treatment. Hence, a CVD awareness program was organized in order to educate adolescents about CVD and its risk factors. Objective: The objectives of the study were to identify students’ …

Sinus Pauses And Asystole As A Rare Presentation Of Thyrotoxic Crisis: A Case Report, Christian Akem Dimala, Charnjeet Sandhu, Oreoluwa Oladiran, Agnieszka Mochon, William Finneran Iii

Transformative Medicine

Introduction

Thyroid crisis is a rare and life-threatening endocrine emergency characterized by exaggerated clinical manifestations of hyperthyroidism with cardiovascular manifestations being the most severe. Rhythm disturbances, sinus tachycardia and atrial fibrillation, are the commonest cardiac manifestations of severe thyrotoxicosis; however, asystole remains a very atypical and uncommon presentation. We present a case of thyrotoxicosis due to Grave’s disease complicated by multiple episodes of asystole.

Case Presentation

A 65-year-old female recently diagnosed with Grave’s disease presented to the hospital with recurrent episodes of syncope. Her hospital course was significant for atrial fibrillation with subsequent progression to sinus pauses and asystole spontaneously …

Study Of Cardiovascular Dynamics During Graded Head-Up Tilt Test In The Young With Syncope Tendency, Martin A. Miranda Sr

Biology and Medicine Through Mathematics Conference

No abstract provided.

Finding The Optimal Ionic Liquid To Target White Blood Cell Subpopulations Using Nanoparticles, Meghan Gorniak

Honors Theses

Disorders and diseases of the immune system have become more prevalent in recent decades and can have life-threatening effects on those afflicted. Granulocyte disorders disproportionately affect infants and children, while chronic lymphocytic leukemia is the most common type of leukemia in adults. Unfortunately, current treatments have many drawbacks such as everyday injection, short-lived efficacy, and unknown levels of safety and effectiveness. It is imperative to find more effective treatment options that could allow for easier drug delivery to specific populations of white blood cells (WBCs). Nanoscale medicine shows promising application, but complications remain in reaching the desired target site and …

Alternate Site Pacing And The Impact On Intracellular Calcium Handling During The Post-Extrasystolic Cardiac Cycle, Kent Ozcan, Lawrence Mulligan

Rowan-Virtua Research Day

Objective: Previous work has shown that alternate site (RV apex) results in myocardial dysfunction. With the development of tools to place endocardial pacing leads in locations that create physiological pacing activation, we sought to evaluate how ventricular trans-septal or left ventricular apical placement pacing differs from right atrial pacing. We will evaluate how these chronic pacing modes impact the PR and RF at baseline, 0, and 16 weeks in the canine heart.

Methods: Quantitative analysis will be performed on previously generated data. The data set includes pacing of 15 dogs total (8 with trans-septal leads & 7 with left ventricular …

Admission Pao2 And Mortality Among Pediatric Icu Patients And Critically Ill Subgroups, Cara Holton

Research Days

Watch recording of live presentation

Background and Objectives: Studies analyzing the association between hyperoxia and mortality in critically ill pediatric patients and those admitted after cardiac arrest are conflicting and limited by small sample sizes. The aim of this study is to evaluate the association between PaO2 on admission to the pediatric ICU and mortality in a heterogeneous, multicenter cohort and among subgroups of critically ill patients.

Methods/Design: A retrospective cohort study was conducted using data from Virtual Pediatric Systems (VPS) database. VPS is a clinical pediatric critical care database with over 135 participating hospitals in North America. All VPS …