Physiology Commons^™

Physiological Responses Of The American Lobster Cardiovascular System To Neuropeptide Sgrnflrfamide (Sgrn), Andre Eden

Honors Projects

During every second of a human’s life, the cardiovascular system is modulated by factors both intrinsic and extrinsic to the physiology of the heart. We can uncover new insights regarding the nature of our system through investigations of similar systems in other model species. One example materializes itself in the form of the American Lobster (Homarus americanus) whose single-chambered heart finds resemblance to the function and anatomy to that of humans. The lobster heart is powered by the cardiac ganglion (CG), a group of neurons that drive contractions of surrounding heart muscles, known as the myocardium. Both the …

Re-Engineering Cardio-Oncology Testing Using Biomimetic Heart Slice Cultures., Jessica Miller

Electronic Theses and Dissertations

28% of drug withdrawal from the market are due to unforeseen disruptions in cardiomyocyte contractility and electrophysiology. The most commonly used platforms for drug testing are in vivo animal models and in vitro cell culture models. While both have been of paramount importance for the discovery and detection of many cardiotoxicities and mechanisms of action, they lack the ability to model an intact human myocardium. This work aims to establish cardiac tissue slices, which are 300-micron thin tissue sections taken from the left ventricular myocardium, as an alternative platform for cardio-oncology studies, specifically cardiotoxicity testing. Additionally, this work aims to …

Amelioration Of Mitochondrial Bioenergetic Dysfunction In Diabetes Mellitus: Delving Into Specialized And Non-Specific Therapeutics For The Ailing Heart, Andrya Jean Durr

Graduate Theses, Dissertations, and Problem Reports

Morbidity and mortality of the diabetic population is influenced by many confounding factors, but cardiovascular disease (CVD), remains the leading cause of death. Mitochondrial dysfunction is central in the development of cardiac contractile dysfunction, with decreased mitochondrial bioenergetic function, increased dependence on free fatty acid utilization, and a decrease in glucose utilization having been shown to contribute to contractile dysfunction. Strategies targeting the amelioration of mitochondrial bioenergetic function are attractive for limiting diabetes-induced heart failure, and preserving health-span. The goals of this dissertation were to assess two mitochondrial-centric approaches for the amelioration of mitochondrial and cardiac contractile dysfunction in diabetes …

Role Of Ataxia Telangiectasia Mutated Kinase In Western-Type Diet-Induced Cardiac Outcomes Under Basal And Ischemic Conditions, Mary Wingard

Electronic Theses and Dissertations

Ataxia-telangiectasia mutated kinase (ATM), a serine/threonine kinase, plays a role in DNA damage repair, redox sensing, and metabolism. In the heart, ATM contributes significantly in the myocardial infarction (MI)-induced cardiac remodeling with effects on fibrosis, hypertrophy, apoptosis and inflammation. This study investigates the role of ATM deficiency in 14 weeks Western-type diet (WD)-induced cardiac outcomes prior to and 1-day post-MI in a sex-specific manner using wild-type (WT) and ATM heterozygous knockout (hKO) mice. In male mice, ATM deficiency induced rapid body weight gain and preload-associated dysfunction, while WT mice displayed afterload-associated dysfunction 14 weeks post-WD. Myocyte apoptosis and hypertrophy were …

Editorial: Recent Advances In Cardiotoxicity Testing, Tamer M. A. Mohamed, Javid Moslehi, Jonathan Satin

Physiology Faculty Publications

No abstract provided.

Cardiomyocyte Deletion Of Bmal1 Exacerbates Qt- And Rr-Interval Prolongation In Scn5a+/Δkpq Mice, Elizabeth A. Schroder, Jennifer L. Wayland, Kaitlyn M. Samuels, Syed F. Shah, Don E. Burgess, Tanya S. Seward, Claude S. Elayi, Karyn A. Esser, Brian P. Delisle

Physiology Faculty Publications

Circadian rhythms are generated by cell autonomous circadian clocks that perform a ubiquitous cellular time-keeping function and cell type-specific functions important for normal physiology. Studies show inducing the deletion of the core circadian clock transcription factor Bmal1 in adult mouse cardiomyocytes disrupts cardiac circadian clock function, cardiac ion channel expression, slows heart rate, and prolongs the QT-interval at slow heart rates. This study determined how inducing the deletion of Bmal1 in adult cardiomyocytes impacted the in vivo electrophysiological phenotype of a knock-in mouse model for the arrhythmogenic long QT syndrome (Scn5a+/ΔKPQ). Electrocardiographic telemetry showed inducing the …

Heart Health: Lifestyle Factors That Influence Cardiovascular Well-Being, Holly K. Sawyer

Honors College Theses

Each year, one in every four deaths in the United States is a result of heart disease. As the leading cause of death among women and men from various ethnicities, heart disease may be overlooked when making everyday life decisions. As a group of genetic and behavioral conditions, heart disease is the number one killer of Americans. This may be due to the typical Western diet and daily life choices such as drinking alcohol or smoking tobacco. Heart diseases including atherosclerosis and coronary artery disease kill ten times more women than breast cancer (Lewis, et al., 2017). White men have …

Potential Role Of The Large Protein Titin In The Development Of Heart Failure, Mary M. Prickett

Senior Theses

I will be exploring the impact of the large protein Titin on heart failure with a preserved ejection fraction (HFpEF). It was hypothesized that myocardial Titin plays a significant role in the progression of HFpEF through isoform, N2BA and N2B, changes. It was hypothesized that an increase in the quantity of N2B Titin, less compliant, and a decrease in N2BA Titin, more compliant, will be observed as HF progresses, contributing to an increase in passive stiffness involved in heart contraction. I will cover a detailed report on the role of Titin in HFpEF and propose research methods to explore further.

Striated Muscle Specific Ribosomal Protein L3-Like: Effect Of Knockout On Cardiac Function And Protein Translation, Laura P. Brown

Theses and Dissertations--Physiology

Ribosomes are the molecular machinery of the cell that catalyzes synthesis of peptides from amino acids. The eukaryotic ribosome is made up of four strands of ribosomal RNA (rRNA) and ~80 ribosomal proteins. While many tissues routinely exhibit variations of ribosomal protein stoichiometry, tissue specific ribosomal proteins are rare. The ribosomal protein with the highest tissue specificity of any ribosomal protein is found in striated muscle, ribosomal protein L3-like (RPL3L). Other than its tissue specificity, association with atrial fibrillation, and chromosomal location, there is little known about the function of RPL3L. However, its ubiquitously expressed paralog, RPL3, has been well …

Role Of Transient Receptor Potential Channels In Epithelial Morphogenesis In Chick Embryo, Trinity Q. Waddell

Theses and Dissertations

Transient Receptor Potential channels (TRP) are a superfamily of cationic specific ionchannels that are regulated by various stimuli such as temperature, pH, mechanical stress, ligandsand ion concentration. The role of TRP channels in disease states such as autosomal dominantpolycystic kidney disease, cancer metastasis, and developmental defects lend credence to thebelief that they play an important part in epithelial morphogenesis events. The development ofsomites, neural tube closure and migration of neural crest cells to form things such as the faceand heart is a good developmental model for the aforementioned cellular processes. We haveshown that TRP channels can be found in the …

Adolescent Binge Alcohol Exposure Effects On Heart Structure And Function, Lizhuo Ai

Master's Theses

More than 5 million underage Americans report binge drinking at least once per month. While the effects of alcohol consumption on the adult heart have been well studied, the impact to the adolescent heart is almost entirely unknown. Adolescents primarily consume alcohol in a binge pattern, which elevates blood alcohol content (BAC) to 0.08 g/dL within 2 hours. During adolescence the body grows rapidly, and the heart must also grow by cellular hypertrophy to meet this increasing demand. Our goal was to determine the impact of adolescent binge alcohol exposure on the heart, using an outbred rat model. This thesis …

Machine-Learning To Stratify Diabetic Patients Using Novel Cardiac Biomarkers And Integrative Genomics, Quincy A. Hathaway, Skyler M. Roth, Mark V. Pinti, Daniel C. Sprando, Amina Kunovac, Andrya J. Durr, Chris C. Cook, Garret K. Fink, Tristen B. Cheuvront, Jasmine H. Grossman, Ghadah A. Aljahli, Andrew D. Taylor, Andrew P. Giromini, Jessica L. Allen, John M. Hollander

Faculty & Staff Scholarship

Background: Diabetes mellitus is a chronic disease that impacts an increasing percentage of people each year. Among its comorbidities, diabetics are two to four times more likely to develop cardiovascular diseases. While HbA1c remains the primary diagnostic for diabetics, its ability to predict long-term, health outcomes across diverse demographics, ethnic groups, and at a personalized level are limited. The purpose of this study was to provide a model for precision medicine through the implementation of machine-learning algorithms using multiple cardiac biomarkers as a means for predicting diabetes mellitus development. Methods: Right atrial appendages from 50 patients, 30 non-diabetic and 20 …

Modeling In The Physiology Classroom, Sowmya Anjur

Faculty Publications & Research

Physiology and Disease is a Biology elective at IMSA that has been developed to be mostly student-centered. Some examples of student projects include modeling heart structure to reflect function and creating LED arduino monitors to measure heart rate. Students also measure their lung capacity and blood pressure to demonstrate correlation of these values with heart rate, and trace the correlation back to neuronal controls. Projects such as these integrate other disciplines such as engineering and conform to NGSS Science and Engineering standards and NGSS Cross cutting Concepts standards. Students take responsibility for their own learning and articulate better on tests.

Myocardial Ischemia Reperfusion Injury: Apoptotic, Inflammatory And Oxidative Stress Role Of Galectin-3, Suhail Al-Salam, Satwat Hashmi

Department of Biological & Biomedical Sciences

Background/aims: Myocardial reperfusion has the potential to salvage the ischemic myocardium after a period of coronary occlusion. Reperfusion, however, can cause a wide spectrum of deleterious effects. Galectin-3 (GAL-3), a beta galactoside binding lectin, is closely associated with myocardial infarction (MI), myocardial fibrosis and heart failure. In our study, we investigated its role in ischemia-reperfusion injuries (IR) as this phenomenon is extremely relevant to the early intervention after acute MI.
Methods: C57B6/J wild type (WT) mice and GAL-3 knockout (KO) mice were used for murine model of IR injury in the heart where a period of 30 minutes ischemia was …

Exogenous Ubiquitin: Role In Myocardial Inflammation And Remodeling Post- Ischemia/Reperfusion Injury, Stephanie Scofield

Electronic Theses and Dissertations

Sympathetic stimulation occurs in the heart after injuries such as ischemia/reperfusion (I/R) and myocardial infarction and affects myocardial remodeling. Prolonged sympathetic stimulation can result in myocardial dysfunction through its effects on cardiac myocyte apoptosis and myocardial fibrosis. Ubiquitin (UB) is well known for its role of tagging old or damaged proteins for degradation via the UB-proteosome pathway. The role of exogenous UB however, is not fully understood. Previously, our lab showed that β-adrenergic receptor (β-AR) stimulation increased levels of extracellular UB in the conditioned media of adult rat ventricular myocytes and that UB inhibits β-AR-stimulated apoptosis. This study investigates the …

Phenotypically Heterogeneous Podoplanin-Expressing Cell Populations Are Associated With The Lymphatic Vessel Growth And Fibrogenic Responses In The Acutely And Chronically Infarcted Myocardium, M Cimini, A Cannata, G Pasquinelli, Marcello Rota, P Goichberg

NYMC Faculty Publications

Cardiac lymphatic vasculature undergoes substantial expansion in response to myocardial infarction (MI). However, there is limited information on the cellular mechanisms mediating post-MI lymphangiogenesis and accompanying fibrosis in the infarcted adult heart. Using a mouse model of permanent coronary artery ligation, we examined spatiotemporal changes in the expression of lymphendothelial and mesenchymal markers in the acutely and chronically infarcted myocardium. We found that at the time of wound granulation, a three-fold increase in the frequency of podoplanin-labeled cells occurred in the infarcted hearts compared to non-operated and sham-operated counterparts. Podoplanin immunoreactivity detected LYVE-1-positive lymphatic vessels, as well as masses of …

Cardiovascular Regulation By Kvβ1.1 Subunit, Jared Tur

USF Tampa Graduate Theses and Dissertations

Heterologous expression systems such as COS-7 cells have demonstrated the profound effects of KCNAB1-3 or Kvβ1-3 proteins on voltage gated potassium channels (Kv) channels. Indeed, in the presence of these β-subunits transiently expressed Kv channels are often modulated in multiple ways. Kv channel membrane expression is often increased in the presence of β-subunits. In addition, non-inactivating Kv currents suddenly become fast-inactivating and fast-inactivating channels become even faster. While much research has demonstrated the profound effects the β-subunits in particular the Kvβ1 subunit have on transiently expressed Kv currents little to date is known of the physiological role it may play. …

Programming Heart Disease: Does Poor Maternal Nutrition Alter Expression Of Cardiac Markers Of Proliferation, Hypertrophy, And Fibrosis In Offspring?, Cathy Chun

Honors Scholar Theses

Maternal malnutrition can affect fetal organogenesis, metabolic processes, and factors involved in developmental regulation. Of the many physiological effects poor maternal nutrition can induce in offspring, one of the most important organs affected is the heart. Cardiovascular disease has been associated with poor maternal diet. It also been suggested that hypertension can originate during impaired intrauterine growth and development. Hypertension can trigger hypertensive heart disease and is associated with numerous heart complications. We hypothesized that poor maternal nutrition would alter critical growth factors associated with normal heart development, specifically, insulin-like growth factor (IGF)-1, IGF-2, transforming growth factor (TGF)β, and connective …

Non-Invasive Determination Of Pre-Clinical Markers Of Cardiovascular Diseases In Low Birth Weight And Maternal Western Diet Guinea Pig Offspring Exposed To A Postnatal Western Diet, Jacky Chiu

Electronic Thesis and Dissertation Repository

Low birth weight (LBW), and maternal Western Diet (WD) consumption have both been independently implicated to increase the risk of developing cardiovascular diseases (CVDs) in later life. These fetal programmed risks are also believed to exacerbate the effects of a postnatal WD pattern. Therefore, resulting in the development of pre-clinical markers of CVDs, such as insulin resistance (IR), coronary circulation disruptions. This thesis aimed to elucidate the roles of sub-optimal in utero growth through placental insufficiency, or chronic maternal WD consumption, and postnatal WD consumption on the long-term programming of CVDs in a guinea pig model. Early pre-clinical markers of …

Cigarette Smoke Increases Cardiomyocyte Ceramide Accumulation And Inhibits Mitochondrial Respiration, Trevor Stanley Tippetts

Theses and Dissertations

Cigarette smoking is a common and lethal worldwide habit, with considerable mortality stemming from its deleterious effects on heart function. While current theories posit altered blood lipids and fibrinogen metabolism as likely mediators, none have explored the role of the sphingolipid ceramide in exacerbating heart function with smoke exposure. Ceramide production is a consequence of cigarette smoke in the lung, and considering ceramide's harmful effects on mitochondrial function, we sought to elucidate the role of ceramide in mediating smoke-induced altered heart mitochondrial respiration. Lung cells were exposed to cigarette smoke extract and heart cells were exposed to the lung-cell conditioned …

Mitochondrial Dynamics: Exploring A Novel Target Against Myocardial Ischemia-Reperfusion Injury, Yi Dong

Wayne State University Dissertations

Mitochondrial fusion and fission, collectively termed mitochondrial dynamics, are among the core mechanisms responsible for maintaining mitochondrial health and functional integrity. Dynamin-related protein 1 (DRP1) is a key regulator of mitochondrial fission. Recent studies suggest that i) mitochondrial dynamics, particularly, mitochondrial fission, serves as a mediator of cell fate in the setting of ischemia-reperfusion (IR) injury, and, ii) inhibition of DRP1 and mitochondrial fission provides cardioprotection against IR injury. However, the precise role of DRP1 translocation to mitochondria in the pathogenesis of myocardial ischemia-reperfusion injury has not been established.

Using an established model of hypoxia-reoxygenation (HR) in cultured HL-1 cardiomyocytes, …

Effect Of Muscle Length On Cross-Bridge Kinetics In Intact Cardiac Trabeculae At Body Temperature, Nima Milani-Nejad, Ying Xu, Jonathan P. Davis, Kenneth S. Campbell, Paul M. L. Janssen

Physiology Faculty Publications

Dynamic force generation in cardiac muscle, which determines cardiac pumping activity, depends on both the number of sarcomeric cross-bridges and on their cycling kinetics. The Frank–Starling mechanism dictates that cardiac force development increases with increasing cardiac muscle length (corresponding to increased ventricular volume). It is, however, unclear to what extent this increase in cardiac muscle length affects the rate of cross-bridge cycling. Previous studies using permeabilized cardiac preparations, sub-physiological temperatures, or both have obtained conflicting results. Here, we developed a protocol that allowed us to reliably and reproducibly measure the rate of tension redevelopment (k_tr; which depends …

Regulation Of Protein Degradation In The Heart By Amp-Activated Protein Kinase, Kedryn K. Baskin, Kedryn K. Baskin

Dissertations & Theses (Open Access)

The degradation of proteins by the ubiquitin proteasome system is essential for cellular homeostasis in the heart. An important regulator of metabolic homeostasis is AMP-activated protein kinase (AMPK). During nutrient deprivation, AMPK is activated and intracellular proteolysis is enhanced through the ubiquitin proteasome system (UPS). Whether AMPK plays a role in protein degradation through the UPS in the heart is not known. Here I present data in support of the hypothesis that AMPK transcriptionally regulates key players in the UPS, which, under extreme conditions can be detrimental to the heart. The ubiquitin ligases MAFbx /Atrogin-1 and MuRF1, key regulators of …

Modeling Cardiac Muscle Mechanics, Lorenzo Sewanan

Senior Theses and Projects

The heart is a complex electro-mechanical system which is intrinsically and intimately linked to physiology and pathology. Cardiac muscle tissue underlies the dynamics of the heart; understanding cardiac muscle tissue allows insight into the working of the heart at a fundamental level. Indeed, models allow a theoretical understanding of systems which necessarily exceeds that of experiment. Here, we describe a novel mathematical model of cardiac muscle mechanics based on functional relations.

Exercise Ameliorates Disruption Of The Dystrophin-Associated Glycoprotein Complex And Fibrosis In The Aging Rat Heart, Yang Lee, Jeffrey M. Hord, Hyo-Bum Kwak, Jong-Hee Kim, John M. Lawler

International Journal of Exercise Science: Conference Proceedings

The dystrophin-glycoprotein complex (DGC) is localized and integrated into the cell membrane. The DGC provides a mechanical link between the cellular cytoskeleton and the extracellular matrix (ECM). In cardiac muscle, disruption of DGC might be involved in mediating cardiac remodeling that occurs with aging, cardiomyopathy, and heart failure through transforming growth factor-beta (TGF-ß). Decorin is a small leucine-rich proteoglycan closely related to the DGC component that binds to collagen. Decorin reduces fibrosis via inhibition of TGF-ß and myofibroblast formation. PURPOSE: To test the hypothesis that exercise training (ET) would alleviate age-related disruption of localization in DGC proteins (dystrophin, α-syntrophin, and …

Age-Associated Disruption Of Molecular Clock Expression In Skeletal Muscle Of The Spontaneously Hypertensive Rat, Mitsunori Miyazaki, Elizabeth Schroder, Stephanie E. Edelmann, Michael E. Hughes, Karl Kornacker, C. William Balke, Karyn A. Esser

Physiology Faculty Publications

It is well known that spontaneously hypertensive rats (SHR) develop muscle pathologies with hypertension and heart failure, though the mechanism remains poorly understood. Woon et al. (2007) linked the circadian clock gene Bmal1 to hypertension and metabolic dysfunction in the SHR. Building on these findings, we compared the expression pattern of several core-clock genes in the gastrocnemius muscle of aged SHR (80 weeks; overt heart failure) compared to aged-matched control WKY strain. Heart failure was associated with marked effects on the expression of Bmal1, Clock and Rora in addition to several non-circadian genes important in regulating skeletal muscle phenotype including …

Distorting The Sarcomere, Kenneth S. Campbell

Physiology Faculty Publications

No abstract provided.

Exercise Attenuates Ctgf Levels, Delaying The Onset Of Fibrosis In The Aging Left Ventricle, Claire N. Canon, Jong-Hee Kim, Sean M. Courtney, Brandon Macias, John M. Lawler

International Journal of Exercise Science: Conference Proceedings

Aging is associated with a progressive increase in collagen (i.e., fibrosis) in the aging heart. Fibrosis is associated with a stiffening of the heart and a decrease in heart function. Previous data (Kwak, 2008) showed that matrix metalloproteinase (MMP) activity in the aging heart is decreased linked to an elevation TIMP-1 (tissue inhibitor of MMPs-1); while exercise training increased TIMP-1 and reduced MMP expression. Connective tissue growth factor (CTGF) is an upstream inhibitor of TIMP-1 and is implicated in diabetes and heart failure. We hypothesized that exercise would decrease CTGF levels, thus reducing fibrosis in the aged left ventricle. Young …

Colocalization And Distribution Of Hcn4 Channels And A Maguk Protein In Mammalian Sinoatrial Myocytes, Padmastuti Akella

Honors Scholar Theses

The sinoatrial node is known as the pacemaker of the heart. It controls the rate at which action potentials are generated and propagate through the sinoatrial myocytes. This thesis is an attempt to identify the colocalization of a specific ion channel (HCN4 channel) with a class of scaffolding protein (MAGUK proteins) within the sinoatrial myocyte. The colocalization of these two variables was performed using immunocytochemistry on murine sinoatrial myocytes and experimental results revealed the existence of a strong colocalization between the two variables. Images collected from the confocal microscope and analyzed using ImageJ software revealed a strong dependent correlation between …