Cardiovascular System Commons^™

Total Synthesis Of Clavatadine A Analogs To Produce A Viable Reversible Inhibitor For Factor Xia, Christopher E. Malmberg

All Master's Theses

Cardiovascular disease has quickly become a major health concern in the United States, with numerous citizens dying from cardiovascular disease each year. Older medications, while effective against cardiovascular disease, are problematic to prescribe. A recently isolated natural product, clavatadine A, selectively inhibits human blood coagulation factor XIa. As a result, the synthesis and biological testing of clavatadine A and synthetic clavatadine A analogues that selectively inhibit factor XIa would represent a new direction in cardiovascular disease research. A potent and selective factor XIa inhibitor has the potential to be a safer replacement for current anticoagulants, such as Warfarin, Pradaxa^{® …}

Gene Electro Transfer Of Plasmid Encoding Vascular Endothelial Growth Factor For Enhanced Expression And Perfusion In The Ischemic Swine Heart, Barbara Y. Hargrave, Robert Strange Jr., Sagar Navare, Michael Stratton, Niculina Burcus, Len Murray, Cathryn Lundberg, Anna A. Bulysheva, Fanying Li, Richard Heller

Bioelectrics Publications

Myocardial ischemia can damage heart muscle and reduce the heart's pumping efficiency. This study used an ischemic swine heart model to investigate the potential for gene electro transfer of a plasmid encoding vascular endothelial growth factor for improving perfusion and, thus, for reducing cardiomyopathy following acute coronary syndrome. Plasmid expression was significantly greater in gene electro transfer treated tissue compared to injection of plasmid encoding vascular endothelial growth factor alone. Higher gene expression was also seen in ischemic versus non-ischemic groups with parameters 20 Volts (p

Vascular Ehlers-Danlos Syndrome: A Rare Disorder Presenting With Focal Convulsions, Shakeel Ahmed, Syed Rehan Ali, Naila Nadeem, Muhammad Hamid

Department of Paediatrics and Child Health

Vascular Ehlers-Danlos Syndrome (VEDS), previously called Ehlers-Danlos syndrome type-IV, is a heterogeneous group of heritable connective tissue disorders characterized by thin, translucent skin, easy bruising, arterial, intestinal, and/or uterine fragility. There is large vessel involvement that leads to arterial rupture often preceded by aneurysm, arteriovenous fistulae, or dissection. Noninvasive imaging studies such as CT angiography and MR angiography are preferred as diagnostic studies for this condition. We are reporting a 4 years old girl who was presented with right sided unilateral convulsions and hypertension. CT angiogram showed stenosis with post-stenotic dilatation of coeliac and superior mesenteric arteries. There were extensive …

Targeting The Small- And Intermediate Conductance Ca2+- Activated Potassium Channels: The Drug Binding Pocket At The Channel/Calmodulin Interface, Meng Cui, Guangrong Qin, Kunqian Yu, M. Scott Bowers, Miao Zhang

Pharmacy Faculty Articles and Research

The small- and intermediate-conductance Ca 2+ -activated potassium (SK/IK) channels play important roles in the regulation of excitable cells in both the central nervous and cardiovascular systems. Evidence from animal models has implicated SK/IK channels in neurological conditions such as ataxia and alcohol use disorders. Further, genome-wide association studies have suggested that cardiovascular abnormalities such as arrhythmias and hypertension are associated with single nucleotide polymorphisms that occur within the genes encoding the SK/IK channels. The Ca 2+ sensitivity of the SK/IK channels stems from a constitutively bound Ca 2+ -binding protein: calmodulin. Small-molecule positive modulators of SK/IK channels have been …

Kir Channel Activation Contributes To Onset And Steady-State Exercise Hyperemia In Humans, Anne R. Crecelius, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

We tested the hypothesis that activation of inwardly rectifying potassium (K_IR) channels and Na⁺-K⁺-ATPase, two pathways that lead to hyperpolarization of vascular cells, contributes to both the onset and steady-state hyperemic response to exercise. We also determined whether after inhibiting these pathways nitric oxide (NO) and prostaglandins (PGs) are involved in the hyperemic response. Forearm blood flow (FBF; Doppler ultrasound) was determined during rhythmic handgrip exercise at 10% maximal voluntary contraction for 5 min in the following conditions: control [saline; trial 1 (T1)]; with combined inhibition of K_IR channels and Na …

Vascular Architecture Of The Liver In Shr And Wky Rats, Charalette Mathwig, Kenneth Willaert

Journal of Undergraduate Research at Minnesota State University, Mankato

The liver is a highly complex vascular organ containing an intricate network of arteries, arterioles, portal veins, veins, venules, and capillaries. This complex network could change in situations related to vascular disease such as hypertension. We examined the vasculature in rat livers by scanning electron microscopy. The tissue was prepared by perfusing either Mercox resin or polyurethane resin into the vasculature. Once the resin polymerized, each liver was placed in concentrated potassium hydroxide to corrode the tissue from the vascular casts. The casts were critical point dried, sputter coated with gold-palladium, and viewed by scanning electron microscopy. Examination of the …

Endothelial And Smooth Muscle-Dependent Vascular Reactivity In Immature Arterialized Collateral Capillaries, Caitlin Koeroghlian

Biomedical Engineering

Peripheral arterial occlusive disease (PAOD) occurs due to the build up of atherosclerotic plaque and reduces blood flow to cause chronic ischemia. Patients with PAOD may experience intermittent claudication, or the pain in limb skeletal muscles due to a decease in blood flow. Collateral arteries can act as a natural bypass and improve blood flow to hypoxic tissue by creating an alternate route for blood to flow, but not all patients with PAOD have pre-existing collateral networks. Animal studies indicate that tissues without pre-existing collateral networks can form de novo collaterals from capillaries following occlusion of a feed artery. Unfortunately, …

A Comparison Of Angiography Versus Intravascular Ultrasound In The Treatment Of Peripheral Arterial Disease, Michael Pompliano

Senior Theses

Peripheral Arterial Disease is a growing epidemic throughout the United States. It is estimated that 8 to 12 million Americans currently suffer from PAD, a disease of the circulatory system that limits blood flow to your hands and feet. This limited blood flow is due to the narrowing of the arteries that supply blood throughout your body and can disrupt the balance of the nerves and tissues that make up your extremities. If left untreated, it can cause irreparable, life- threatening damage that may result in amputation of the diseased limb. Although the mechanism of PAD is known and well …

Variability Of M-Mode Versus Two-Dimensional Echocardiography Measurements In Children With Dilated Cardiomyopathy., Caroline K. Lee, Renee Margossian, Lynn A. Sleeper, Charles E. Canter, Shan Chen, Lloyd Y. Tani, Girish S. Shirali, Anita Szwast, Elif Seda Selamet Tierney, M Jay Campbell, Fraser Golding, Yanli Wang, Karen Altmann, Steven D. Colan, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

M-mode and 2-dimensional (2D) echocardiographic imaging are routinely used to quantify left-ventricular (LV) size and function in pediatric patients with dilated cardiomyopathy (DCM). The reproducibility of and correlation between these techniques are unknown. This analysis sought to compare interreader, intrareader, and interacquisition reproducibility of M-mode versus 2D measurements in pediatric DCM patients. The Ventricular Volume Variability study of the Pediatric Heart Network is a multicenter, prospective, observational study assessing the course of chronic DCM in children. Two sonographers performed baseline image acquisitions locally, and two readers performed measurements at the echocardiographic core laboratory. One reader repeated measurements 1 month later. …

Intensity Of Exercise And Endothelial Function In Healthy Adults, Jacquelyn R. Moxey

Human Movement Studies & Special Education Theses & Dissertations

PURPOSE: To examine the effects of acute bouts of isocaloric exercise at different intensities on endothelial function. The flow-mediated dilation (FMD) responses after the different acute exercise bouts were compared to a control (no exercise) condition. METHODS: Nine healthy subjects completed the study (6 males, 3 females, X ± SD = 24 ± 5 yr, 1.75 ± 0.11 m, 79.2 ± 12.4 kg, 47.9 ± 6.9 mL•kg^-1•min^-1). Vascular responses were compared under three different conditions- HIT: a bout of high-intensity interval treadmill exercise consisting of ten 1-minute intervals at ~100% VO_2max; MOD: moderate-intensity exercise …

Variation In Feeding Practices Following The Norwood Procedure., Linda M. Lambert, Nancy A. Pike, Barbara Medoff-Cooper, Victor Zak, Victoria L. Pemberton, Lisa Young-Borkowski, Martha L. Clabby, Kathryn N. Nelson, Richard G. Ohye, Bethany Trainor, Karen Uzark, Nancy Rudd, Louise Bannister, Rosalind Korsin, David S. Cooper, Christian Pizarro, Sinai C. Zyblewski, Bronwyn H. Bartle, Richard V. Williams, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

OBJECTIVES: To assess variation in feeding practice at hospital discharge after the Norwood procedure, factors associated with tube feeding, and associations among site, feeding mode, and growth before stage II.

STUDY DESIGN: From May 2005 to July 2008, 555 subjects from 15 centers were enrolled in the Pediatric Heart Network Single Ventricle Reconstruction Trial; 432 survivors with feeding data at hospital discharge after the Norwood procedure were analyzed.

RESULTS: Demographic and clinical variables were compared among 4 feeding modes: oral only (n = 140), oral/tube (n = 195), nasogastric tube (N-tube) only (n = 40), and gastrostomy tube (G-tube) only …

Leptin Regulates Cd16 Expression On Human Monocytes In A Sex-Specific Manner, Joseph G. Cannon, Gyanendra Sharma, Gloria Sloan, Christiana Dimitropoulou, R. Randall Baker, Andrew Mazzoli, Barbara Kraj, Anthony Mulloy, Miriam Cortez-Cooper

School of Medical Diagnostics & Translational Sciences Publications

Fat mass is linked mechanistically to the cardiovascular system through leptin, a 16 kDa protein produced primarily by adipocytes. In addition to increasing blood pressure via hypothalamic-sympathetic pathways, leptin stimulates monocyte migration, cytokine secretion, and other functions that contribute to atherosclerotic plaque development. These functions are also characteristics of CD16-positive monocytes that have been implicated in the clinical progression of atherosclerosis. This investigation sought to determine if leptin promoted the development of such CD16-positive monocytes. Cells from 45 healthy men and women with age ranging from 20 to 59 years were analyzed. Circulating numbers of CD14++16++ monocytes, which are primary …

Bioengineered Hearts, Rivky Loeb

The Science Journal of the Lander College of Arts and Sciences

Heart disease is one of the highest causes for fatality in the world. Although many such diseases can be treated by a heart transplant, this in itself can cause countless problems. Aside from the high demand for donor hearts, there is the risk of the patient’s immune system rejecting the transplanted heart. A bioengineered heart would reduce the need for donor hearts, and thus save countless lives. Finding a suitable scaffold, obtaining appropriate cells, and ensuring that the tissue will function properly are the main focuses in creating an artificial heart. While most of the studies done have been concentrated …

Alterations And Specifications Of Excess Post-Exercise Oxygen Consumption: A Review, Genevieve Kocoloski, Anne R. Crecelius

Health and Sport Science Faculty Publications

This review describes oxygen consumption, both in terms of a goal of weight management and aerobic training. It introduces excess postexercise oxygen consumption (EPOC) and the benefits that can come from it. EPOC can aid in weight management as a means to continue to expend energy even after exercise has ceased. This review also discusses the many determinants of EPOC and analyzes the effects of various conditions on the elevated consumption. Such conditions include duration and intensity of exercise, training status, and supplementation. Later discussed are the possible underlying mechanisms and how they are responsible for EPOC. Although they have …

Role Of Cardiac Catecholamines In Embryos And Adults Under Stress, Candice Baker

Electronic Theses and Dissertations

Cardiovascular disease is responsible for the loss of one life every 38 seconds and accounts for 26.6 percent of all infants that die of congenital birth defects. Adrenergic hormones are critically important regulators of cardiovascular physiology in embryos and adults. They are key mediators of stress responses and have profound stimulatory effects on cardiovascular function, and dysregulation of adrenergic function has been associated with many adverse cardiac conditions, including congenital malformations, arrhythmias, ischemic heart disease, heart failure, and sudden cardiac death. Despite intensive study, the specific roles these hormones play in the developing heart is not well-understood. Further, there is …

Effects Of Endogenous Cannabinoid Anandamide On Voltage-Dependent Sodium And Calcium Channels In Rat Ventricular Myocytes, Lina T. Al Kury, Oleg I. Voitychuk, Keun-Hang Susan Yang, Faisal T. Thayyullathil, Petro Doroshenkp, Ali M. Ramez, Yaroslav M. Shuba, Sehamuddin Galadari, Frank Christopher Howarth, Murat Oz

Mathematics, Physics, and Computer Science Faculty Articles and Research

BACKGROUND AND PURPOSE: The endocannabinoid anandamide (N-arachidonoyl ethanolamide; AEA) exerts negative inotropic and antiarrhythmic effects in ventricular myocytes.

EXPERIMENTAL APPROACH: Whole-cell patch-clamp technique and radioligand-binding methods were used to analyse the effects of anandamide in rat ventricular myocytes.

KEY RESULTS: In the presence of 1-10 μM AEA, suppression of both Na(+) and L-type Ca(2+) channels was observed. Inhibition of Na(+) channels was voltage and Pertussis toxin (PTX) - independent. Radioligand-binding studies indicated that specific binding of [(3) H] batrachotoxin (BTX) to ventricular muscle membranes was also inhibited significantly by 10 μM metAEA, a non-metabolized AEA analogue, with …

Multicenter Study Comparing Shunt Type In The Norwood Procedure For Single-Ventricle Lesions: Three-Dimensional Echocardiographic Analysis., Gerald R. Marx, Girish S. Shirali, Jami C. Levine, Lin T. Guey, James F. Cnota, Jeanne M. Baffa, William L. Border, Steve Colan, Gregory Ensing, Mark K. Friedberg, David J. Goldberg, Salim F. Idriss, J Blaine John, Wyman W. Lai, Minmin Lu, Shaji C. Menon, Richard G. Ohye, David Saudek, Pierre C. Wong, Gail D. Pearson, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: The Pediatric Heart Network's Single Ventricle Reconstruction (SVR) trial randomized infants with single right ventricles (RVs) undergoing a Norwood procedure to a modified Blalock-Taussig or RV-to-pulmonary artery shunt. This report compares RV parameters in the 2 groups using 3-dimensional echocardiography.

METHODS AND RESULTS: Three-dimensional echocardiography studies were obtained at 10 of 15 SVR centers. Of the 549 subjects, 314 underwent 3-dimensional echocardiography studies at 1 to 4 time points (pre-Norwood, post-Norwood, pre-stage II, and 14 months) for a total of 757 3-dimensional echocardiography studies. Of these, 565 (75%) were acceptable for analysis. RV volume, mass, mass:volume ratio, ejection fraction, …

Six-Minute Walk Test Performance In Healthy Adult Pakistani Volunteers, Nisar Ahmed Rao, Muhammad Irfan, Ahmed Suleman Haque, Ali Bin Sarwar Zubairi, Safia Awan

Section of Pulmonary & Critical Care

Objective: To determine the six-minute walking distance (6MWD) for healthy Pakistanis, identify factors affecting 6MWD, compare published equations with the local data and derive an equation. Study Design: Cross-sectional study. Place and Duration of Study: Two medical institutes of Karachi, from January to May 2011. Methodology: Subjects between 15 and 65 years were prospectively enrolled after screening. A standardized 6MWT was administered. SpO2, HR, BP and dyspnoea scores were determined pre- and post-test. Results: Two hundred and eleven (71%) men and 85 (29%) women participated. Mean 6MWD was 469.88 ± 101.24 m: men walked 502.35 ± 92.21 m and women …

Factors Impacting Echocardiographic Imaging After The Fontan Procedure: A Report From The Pediatric Heart Network Fontan Cross-Sectional Study., Richard V. Williams, Renee Margossian, Minmin Lu, Andrew M. Atz, Timothy J. Bradley, Michael Jay Campbell, Steven D. Colan, Dianne Gallagher, Wyman W. Lai, Gail D. Pearson, Ashwin Prakash, Girish S. Shirali, Meryl S. Cohen, Pediatric Heart Network Investigators

Manuscripts, Articles, Book Chapters and Other Papers

Echocardiographic image quality in Fontan survivors may be limited by a variety of factors. We sought to describe echocardiographic quality and factors associated with study quality in subjects participating in the Pediatric Heart Network Fontan Cross-Sectional Study. Echocardiograms were obtained at 7 clinical sites using a standard protocol. Quality grading and analysis were performed by a core laboratory. Univariate and multivariable modeling were performed to assess factors associated with quality and ability to obtain images sufficient for prespecified quantitative analysis. A total of 543 echocardiograms were obtained. The quality of echocardiograms improved over the duration of the study. The great …

Reactive Hyperemia Occurs Via Activation Of Inwardly Rectifying Potassium Channels And Na+/K+-Atpase In Humans, Anne R. Crecelius, Jennifer C. Richards, Gary J. Luckasen, Dennis G. Larson, Frank A. Dinenno

Health and Sport Science Faculty Publications

Rationale: Reactive hyperemia (RH) in the forearm circulation is an important marker of cardiovascular health, yet the underlying vasodilator signaling pathways are controversial and thus remain unclear.

Objective: We hypothesized that RH occurs via activation of inwardly rectifying potassium (K_IR) channels and Na⁺/K⁺-ATPase and is largely independent of the combined production of the endothelial autocoids nitric oxide (NO) and prostaglandins in young healthy humans.

Methods and Results: In 24 (23±1 years) subjects, we performed RH trials by measuring forearm blood flow (FBF; venous occlusion plethysmography) after 5 minutes of arterial occlusion. In protocol 1, …