Cardiovascular System Commons^™

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 …

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, …

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 …

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 …

Severe Lamotrigine Neurotoxicity Treated With Intralipid Emulsion Therapy, Philip W. Moore Do, Megan C. Urquhart Do, Dale L. Mcmillion Do, Keith K. Burkhart Md, Louis R. Cantilena Jr, Md, J Ward Donovan Md

Department of Emergency Medicine

No abstract provided.

Enalapril In Infants With Single Ventricle: Results Of A Multicenter Randomized Trial., Daphne T. Hsu, Victor Zak, Lynn Mahony, Lynn A. Sleeper, Andrew M. Atz, Jami C. Levine, Piers C. Barker, Chitra Ravishankar, Brian W. Mccrindle, Richard V. Williams, Karen Altmann, Nancy S. Ghanayem, Renee Margossian, Wendy K. Chung, William L. Border, Gail D. Pearson, Mario P. Stylianou, Seema Mital, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin-converting enzyme inhibitor therapy improves clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology have poor growth and are at risk for abnormalities in ventricular systolic and diastolic function. The ability of angiotensin-converting enzyme inhibitor therapy to preserve ventricular function and improve somatic growth and outcomes in these infants is unknown.

METHODS AND RESULTS: The Pediatric Heart Network conducted a double-blind trial involving 230 infants with single-ventricle physiology randomized to receive enalapril (target dose 0.4 mg . kg(-1) . d(-1)) or placebo who were followed up until 14 months of age. The primary end …

Fetal Programming By Nicotine Increases Cardiac Susceptibility To Ischemic Injury, Jennifer Charlotte Alexie Lawrence

Loma Linda University Electronic Theses, Dissertations & Projects

Fetal programming is the area of study that focuses on the prenatal origins of adult onset disorders. Previous studies have associated an adverse prenatal environment with the onset of physiologic and metabolic diseases during adulthood. Fetal malnutrition, hypoxia, and exposure to drugs - such as cocaine and nicotine - have been associated with adult disease states. Cigarette smoking is the number one cause of preventable death in the developed world. Among the many dangerous chemicals found in tobacco products is nicotine, the compound responsible for the addictive nature of tobacco use. Nicotine use during pregnancy is a known cause of …

Fetal Cocaine Exposure Causes Epigenetic Changes In The Rat Heart, Kurt D. Meyer

Loma Linda University Electronic Theses, Dissertations & Projects

Cocaine abuse continues to be prevalent in the United States and other industrialized nations, in addition to the negative health effects that cocaine abuse has on the user, a mother who uses cocaine while pregnant also exposes the developing fetus to cocaine. Although there have been many studies of the effects of cocaine on the adult heart, studies of cocaine on the fetal heart and its potential delayed pathophysiological effects on cardiac function in adult offspring are extremely limited. The studies of the present project sought to enhance the understanding of the effect of cocaine exposure on the fetal heart …

Rationale And Design Of A Trial Of Angiotensin-Converting Enzyme Inhibition In Infants With Single Ventricle., Daphne T. Hsu, Seema Mital, Chitra Ravishankar, Renee Margossian, Jennifer S. Li, Lynn A. Sleeper, Richard V. Williams, Jami C. Levine, Brian W. Mccrindle, Andrew M. Atz, Darlene Servedio, Lynn Mahony, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Angiotensin converting enzyme (ACE) inhibitors are known to improve clinical outcome and ventricular function in adults with heart failure. Infants with single-ventricle physiology show abnormalities in ventricular function as well as poor growth. The ability of an ACE inhibitor to preserve ventricular function and improve growth in these infants is unknown.

METHODS: The Pediatric Heart Network designed a randomized, double-blind trial to compare outcomes in infants with single-ventricle physiology receiving enalapril or placebo. Neonates < or =45 days old were eligible. The primary outcome is weight-for-age Z-score at 14 months of age. Secondary outcomes include other measures of somatic growth, laboratory and functional measures of heart failure, developmental indices, measures of ventricular size and function, and the relationship of the renin-angiotensin-aldosterone system genotype to the response to enalapril. The incidence and spectrum of adverse events will also be compared between treatment groups.

RESULTS: A total of 1,245 neonates were screened and 533 (43%) were eligible. The consent rate was 43%; 230 subjects were enrolled. Parental reluctance to …

Dextran-Methylprednisolone Succinate As A Prodrug Of Methylprednisolone: Plasma And Tissue Disposition, Xiaoping Zhang, Reza Mehvar

Pharmacy Faculty Articles and Research

Plasma and tissue disposition of a macromolecular prodrug of methylprednisolone (MP), dextran (70 kDa)–methylprednisolone succinate (DMP), was studied in rats. Single 5‐mg/kg doses of DMP or unconjugated MP were administered into the tail veins of different groups of rats (n  = 4/group/time point). Blood (cardiac puncture) and tissues (liver, spleen, kidney, heart, lung, thymus, and brain) were collected at various times after DMP (0–96 h) or MP (0–2 h) injections. Concentrations of DMP and MP in samples were analyzed by size‐exclusion chromatography (SEC) and reversed‐phase high‐performance liquid chromatography (HPLC), respectively. Conjugation of MP with 70‐kDa dextran resulted in 22‐, …

Regulation Of Connexin43 By Phosphorylation, Maithili M. Shah

Loma Linda University Electronic Theses, Dissertations & Projects

Gap junctions play a crucial role in embryogenesis, especially of the heart where connexin43 is thought to be important for its formation as well as synchronized contraction. Several reports have shown that connexin43 protein is phosphorylated on serine residues in vitro and in vivo.

Studies performed in our laboratory have demonstrated that cell-to-cell communication in cells expressing connexin43 can be controlled rapidly and reversibly by microinjection of active protein kinases or phosphatases that target serine or threonine residues. Phosphorylation by cAMP-dependent protein kinase (PKA) seems to favor channel opening, whereas the effect of protein kinase C (PKC) on channel gating …

A Cytochemical Evaluation Of Blood-Brain Barrier Sodium, Potassium- And Calcium-Adenosine Triphosphatase Polarity, Panya Steve Manoonkitiwongsa

Loma Linda University Electronic Theses, Dissertations & Projects

The blood-brain barrier (BBB) is formed by cerebral vascular endothelial cells. Brain ion and fluid homeotasis essential for proper neural functioning is due to the BBB. Sodium-potassium and calcium-activated adenosine triphosphatase (Na⁺, K⁺-ATPase and Ca²⁺-ATPase) serve as one of the main mechanisms controlling brain Na⁺, K⁺, and Ca²⁺ concentrations. The present accepted concept is that both of these enzymes are localized to the abluminal plasma membrane of endothelial cells although there have been contrary results from some studies. Because of these discrepancies, further work was needed. Various cytochemical procedures …

Effect Of Cocaine On Rabbit Renin Angiotensin System: Cocaine Detection In Adult And Fetal Tissue And Adult Plasma Using Ion Mobility Spectrometry, Barbara Belinda Guinn

Biological Sciences Theses & Dissertations

Ion mobility spectrometry (IMS) was used to detect cocaine and/or the metabolite ecgonine methyl ester (EME) in tissue and plasma samples from male, maternal, and fetal New Zealand White (NZW) rabbits. EME was consistently detected in all adult plasma samples 5 minutes after the injection of cocaine hydrochloride (cocaine•HCI, 2 mg/kg). EME was also in the liver, kidneys, testicles, and ovaries. Five minutes after the injection of cocaine•HCI, the male arterial pressure (MAP) increased from a mean control value of 79 ± 3.2 mmHg to 88 ± 4.1 mmHg, and the pCO₂ increased from a control value of28 ± …

Fetal Whole-Body Fluid, Cardiovascular And Endocrine Dynamics : Computer Analysis Of Regulatory Mechanisms, Peter Stuart Gold

Loma Linda University Electronic Theses, Dissertations & Projects

The dynamics of transcapillary fluid and protein distribution and endocrine regulation of cardiovascular function were studied in chronically instrumented fetal sheep during the third trimester. Average experimental changes in vascular pressures, blood volume, plasma hormone concentrations, hematocrit and plasma protein concentration were analyzed using mathematical modeling and parameter optimization techniques in order to determine values for the major parameters which regulate fluid, protein and endocrine dynamics and to determine endocrine dose-response relationships to changes in cardiovascular function. The hormones which were considered are arginine vasopressin (AVP), angiotensin II (AII), epinephrine (EPI) and norepinephrine (NE). Vascular disturbances which were considered include …

The Synthesis And Evaluation Of The Cardiovascular Activity Of Novel Imidazole Ring Systems, Joseph E. De Los Angeles

Chemistry & Biochemistry Theses & Dissertations

An investigation was undertaken to synthesize and evaluate the cardiovascular activity of two imidazole ring systems. Imidazoles with hypotensive activity would provide novel potential antihypertensive drugs. These novel structures may also find use as chemical probes in the study of the cardiovascular system and as prototypes for other potential cardiovascular agents.

The histamine derivative, 7,7-dipyridyl-4,5,6,7-tetrahydroimidazo-[4,5-c]pyridine (ligand l), was demonstrated to possess significant hypotensive activity in laboratory rats. A 15 mg/Kg dose of ligand 1 produces a statistically significant decrease in blood pressure when injected IP. This hypotensive effect is also associated with marked increase in heart rate. Although compound 1 …

The Circulatory Effects Of Histamine, Fred B. Moor

Medical Arts and Sciences: A Scientific Journal of the College of Medical Evangelists

No abstract provided.