Cardiology Commons^™

An Uncommon Complication During Trans-Aortic Valve Replacement, Sanjeev Nair Md, Yassir Nawaz Md, Nainesh C. Patel Md, David A. Cox Md, William Combs Md, Raymond L. Singer Md, J Patrick Kleaveland Md

Department of Medicine

No abstract provided.

Mitoquinone (Mitoq) Exerts Antioxidant Effects Independent Of Mitochondrial Targeted Effects In Phorbol-12-Myristate-13-Acetate (Pma) Or N-Formyl-L-Methiony-L-Leucyl-L-Phenylalanine (Fmlp) Stimulated Polymorphonuclear Leukocyte (Pmn) Superoxide (So) Release, Matthew Lepera, D. Pesikan, J. Voeun, Kerry-Anne Perkins, Qian Chen, Robert J. Barsotti, Lindon H. Young

Research Day

MitoQ is a mitochondrial-targeted coenzyme Q antioxidant analog that dose-dependently restored cardiac function and reduced infarct size in isolated perfused rat hearts subjected to ischemia reperfusion (I/R). Moreover, mitoQ also dose-dependently attenuated PMA stimulated PMN superoxide (SO) release at the same concentration (10uM) as the cardioprotective dose. NADPH oxidase is the principle source of PMN SO release. We speculate that mitoQ may exert antioxidant effects independent of the mitochondria. Therefore, we hypothesized that inhibition of mitoQ on PMN-SO release will be similar as other coenzyme Q analogs: coenzyme Q1 and decylubiquinone without affecting cell viability. SO release was measured spectrophotometrically …

Gp91ds-Tat, A Selective Nadph Oxidase Peptide Inhibitor, Increases Blood Nitric Oxide (No) Bioavailability In Bind Limb Ischemia And Reperfusion (I/R), Sydney Walker, Tyler Galbreath, Qian Chen, Robert J. Barsotti, H. Patel, William Chau, Lindon H. Young

Research Day

I/R injury induces cell death and organ dysfunction in part due to a burst of reactive oxygen species that occurs upon the reintroduction of oxygen into the ischemic area, leading to endothelial dysfunction: decreased blood NO and increased hydrogen peroxide (H2O2 ) levels. We’ve previously shown in isolated rat hearts subjected to I/R injury, gp91ds-tat attenuated cardiac contractile dysfunction and reduced infarct size compared to controls presumably by the inhibition of NADPH oxidase induced superoxide release. Superoxide can quench NO via the formation of peroxynitrite and also be converted to H2O2 in blood. We attempted to confirm this hypothesis using …

Cyclic Nucleotide-Dependent Phosphorylation Regulates Bk-Ca Channel Activity In Human Coronary Artery Smooth Muscle Cells, Raeonda Williams

PCOM Biomedical Studies Student Scholarship

Cardiovascular diseases (CVD) can induce dysfunction in organ systems by attenuating normal blood flow. Gonadal steroids are vasoactive hormones, but their role in contributing to cardiovascular function remains controversial. We have demonstrated that gonadal steroids can relax coronary arteries by opening the large-conductance, calcium- and voltage-activated potassium (BKca) channel in smooth muscle cells by increasing cyclic nucleotide levels; however, the signaling pathways involved remain to be elucidated. The purpose of this study was to identify how phosphorylation (via cAMP- and cGMP-dependent protein kinases) I dephosphorylation (via phosphoprotein phosphatase 2A, PP2A) regulates BKca channel activity in human coronary artery smooth muscle …

Bisphenol A Increases Atherosclerosis In Pregnane X Receptor-Humanized Apoe Deficient Mice, Yipeng Sui, Se-Hyung Park, Robert N. Helsley, Manjula Sunkara, Frank J. Gonzalez, Andrew J. Morris, Changcheng Zhou

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: Bisphenol A (BPA) is a base chemical used extensively in many consumer products. BPA has recently been associated with increased risk of cardiovascular disease (CVD) in multiple large-scale human population studies, but the underlying mechanisms remain elusive. We previously reported that BPA activates the pregnane X receptor (PXR), which acts as a xenobiotic sensor to regulate xenobiotic metabolism and has pro-atherogenic effects in animal models upon activation. Interestingly, BPA is a potent agonist of human PXR but does not activate mouse or rat PXR signaling, which confounds the use of rodent models to evaluate mechanisms of BPA-mediated CVD risk. …

Are Cardiovascular Risk Factors Responsible For The U-Shaped Relationship Between Running And Longevity? The Masters Athletic Study, Adrian C. Bell Do, Courtney Bennett Do, Martin E. Matsumura Md

Department of Medicine

No abstract provided.

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 …

The Role Of Bioactive Lipids In Stem Cell Mobilization And Homing: Novel Therapeutics For Myocardial Ischemia, Yuri M. Klyachkin, Anush V. Karapetyan, Mariusz Z. Ratajczak, Ahmed Abdel-Latif

Saha Cardiovascular Research Center Faculty Publications

Despite significant advances in medical therapy and interventional strategies, the prognosis of millions of patients with acute myocardial infarction (AMI) and ischemic heart disease (IHD) remains poor. Currently, short of heart transplantation with all of its inherit limitations, there are no available treatment strategies that replace the infarcted myocardium. It is now well established that cardiomyocytes undergo continuous renewal, with contribution from bone marrow (BM)-derived stem/progenitor cells (SPCs). This phenomenon is upregulated during AMI by initiating multiple innate reparatory mechanisms through which BMSPCs are mobilized towards the ischemic myocardium and contribute to myocardial regeneration. While a role for the SDF-1/CXCR4 …

Reduction Of Vldl Secretion Decreases Cholesterol Excretion In Niemann-Pick C1-Like 1 Hepatic Transgenic Mice, Stephanie M. Marshall, Kathryn L. Kelley, Matthew A. Davis, Martha D. Wilson, Allison L. Mcdaniel, Richard G. Lee, Rosanne M. Crooke, Mark J. Graham, Lawrence L. Rudel, J. Mark Brown, Ryan E. Temel

Saha Cardiovascular Research Center Faculty Publications

An effective way to reduce LDL cholesterol, the primary risk factor of atherosclerotic cardiovascular disease, is to increase cholesterol excretion from the body. Our group and others have recently found that cholesterol excretion can be facilitated by both hepatobiliary and transintestinal pathways. However, the lipoprotein that moves cholesterol through the plasma to the small intestine for transintestinal cholesterol efflux (TICE) is unknown. To test the hypothesis that hepatic very low-density lipoproteins (VLDL) support TICE, antisense oligonucleotides (ASO) were used to knockdown hepatic expression of microsomal triglyceride transfer protein (MTP), which is necessary for VLDL assembly. While maintained on a high …

Aortic Aneurysms In Loeys-Dietz Syndrome - A Tale Of Two Pathways?, Frank Davis, Debra L. Rateri, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

Loeys-Dietz syndrome (LDS) is a connective tissue disorder that is characterized by skeletal abnormalities, craniofacial malformations, and a high predisposition for aortic aneurysm. In this issue of the JCI, Gallo et al. developed transgenic mouse strains harboring missense mutations in the genes encoding type I or II TGF-β receptors. These mice exhibited several LDS-associated phenotypes. Despite being functionally defective, the mutated receptors enhanced TGF-β signaling in vivo, inferred by detection of increased levels of phosphorylated Smad2. Aortic aneurysms in these LDS mice were ablated by treatment with the Ang II type 1 (AT1) receptor antagonist losartan. The results from this …

Sphingosine-1-Phosphate-Mediated Mobilization Of Hematopoietic Stem/Progenitor Cells During Intravascular Hemolysis Requires Attenuation Of Sdf-1-Cxcr4 Retention Signaling In Bone Marrow, Kasia Mierzejewska, Yuri M. Klyachkin, Janina Ratajczak, Ahmed Abdel-Latif, Magda Kucia, Mariusz Z. Ratajczak

Saha Cardiovascular Research Center Faculty Publications

Sphingosine-1-phosphate (S1P) is a crucial chemotactic factor in peripheral blood (PB) involved in the mobilization process and egress of hematopoietic stem/progenitor cells (HSPCs) from bone marrow (BM). Since S1P is present at high levels in erythrocytes, one might assume that, by increasing the plasma S1P level, the hemolysis of red blood cells would induce mobilization of HSPCs. To test this assumption, we induced hemolysis in mice by employing phenylhydrazine (PHZ). We observed that doubling the S1P level in PB from damaged erythrocytes induced only a marginally increased level of mobilization. However, if mice were exposed to PHZ together with the …

Amlodipine Reduces Angii-Induced Aortic Aneurysms And Atherosclerosis In Hypercholesterolemic Mice, Xiaofeng Chen, Debra L. Rateri, Deborah A. Howatt, Anju Balakrishnan, Jessica J. Moorleghen, Andrew J. Morris, Richard Charnigo, Lisa A. Cassis, Alan Daugherty

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND: The purpose of this study was to determine effects of amlodipine, a dihydropyridine calcium channel blocker, on development of angiotensin II (AngII)-induced vascular pathologies.

METHODS AND RESULTS: Male LDL receptor -/- mice were infused with vehicle, amlodipine (5 mg/kg/d), AngII (1,000 ng/kg/min), or AngII + amlodipine for 4 weeks through osmotic pumps (n=10/group). Mice were fed a saturated fat-enriched diet for 1 week prior to pump implantation and during 4 weeks of infusion. Infusion of amlodipine resulted in plasma concentrations of 32 ± 2 ng/ml and 27 ± 2 ng/ml for mice in saline + amlodipine and AngII + …

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, …

Successful Long-Term Extracorporeal Cardiopulmonary Membrane Oxygenation Without Anti-Coagulation, Janissa Nair, Dorothea T. Watson Do, Rita Pechulis Md, Fccp, Nicholas M. Rini Pa-C, Timothy S. Misselbeck, Kenneth Miller Rrt, James K. Wu Md

Department of Surgery

No abstract provided.

Calpain-2 Compensation Promotes Angiotensin Ii-Induced Ascending And Abdominal Aortic Aneurysms In Calpain-1 Deficient Mice, Venkateswaran Subramanian, Jessica J. Moorleghen, Anju Balakrishnan, Deborah A. Howatt, Athar H. Chishti, Haruhito A. Uchida

Saha Cardiovascular Research Center Faculty Publications

BACKGROUND AND OBJECTIVE: Recently, we demonstrated that angiotensin II (AngII)-infusion profoundly increased both aortic protein and activity of calpains, calcium-activated cysteine proteases, in mice. In addition, pharmacological inhibition of calpain attenuated AngII-induced abdominal aortic aneurysm (AA) in mice. Recent studies have shown that AngII infusion into mice leads to aneurysmal formation localized to the ascending aorta. However, the precise functional contribution of calpain isoforms (-1 or -2) in AngII-induced abdominal AA formation is not known. Similarly, a functional role of calpain in AngII-induced ascending AA remains to be defined. Using BDA-410, an inhibitor of calpains, and calpain-1 genetic deficient mice, …

Effects Of Prior Acute Exercise On Circulating Cytokine Concentration Responses To A High-Fat Meal, Josef Brandauer, Rian Q. Landers-Ramos, Nathan T. Jenkins, Espen E. Spangenburg, James M. Hagberg, Steven J. Prior

Health Sciences Faculty Publications

High-fat meal consumption alters the circulating cytokine profile and contributes to cardiometabolic diseases. A prior bout of exercise can ameliorate the triglyceride response to a high-fat meal, but the interactive effects of exercise and high-fat meals on cytokines that mediate cardiometabolic risk are not fully understood. We investigated the effects of prior exercise on the responses of circulating tumor necrosis factor-a (TNF-a), interleukin-6 (IL-6), IL-8, leptin, retinol-binding protein 4 (RBP4), vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), placental growth factor (PlGF), and soluble fms-like tyrosine kinase-1 (sFlt-1) to a high-fat meal. Ten healthy men were studied before …

Post-Prandial Upright Exercise Echocardiography In Hypertrophic Cardiomyopathy, Ellina C. Feiner Md, Milla Arabadjian Fnp, Glenda Winson Rn, Bette Kim Md, Farooq Chaudhry Md, Mark V. Sherrid Md

Department of Medicine

No abstract provided.

Durability, Reliability, Viability: 48 Year-Survival Of A Starr-Edwards Mitral Valve, Bilal Ayub, Justin L. Guthier, James K. Wu

Department of Medicine

No abstract provided.

Use Of An Ed-Based Observation Unit Followed By Outpatient Stress Testing In Chest Pain Patients With Prior Coronary Artery Disease History: Evaluation Of Safety And Prognostic Utility, Yasser Khalil Md, Prasant Pandey Md, Melvin H. Schwartz Md, Maida Abdul-Latif Md, Martin E. Matsumura Md

Department of Medicine

No abstract provided.

Comparison Of Chronic Persistent And Post-Operative Atrial Fibrillation On Long Term Survival In Patients Undergoing Cardiac Valve Surgery, Nasir Shariff, Ravi V. Desai Md, Sherrine Eid, Michael J. Weiss, Matthew W. Martinez, Sultan M. Siddique, Ronald S. Freudenberger Md

Department of Medicine

No abstract provided.

Pre-Operative Angiotensin Converting Enzyme Inhibitors And Angiotensin Receptor Blockers On The Occurrence Of Post Operative Atrial Fibrillation After Cardiac Valve Department Of Surgery, Nasir Shariff, Matthew W. Martinez Md, Ravi V. Desai Md, Michael J. Weiss, Vadim Levin Md, Larry E. Jacobs Md, Martin E. Matsumura Md, Ronald S. Freudenberger Md

Department of Medicine

No abstract provided.

Intracardiac Echocardiogram In Patient With Patent Foramen Ovale And Obstructive Sleep Apnea, Hassam Saif Md, Shameer Ahmed Md, Bilal Ayub Md, Bryan W. Kluck Do

Department of Medicine

No abstract provided.

Relationship Between Exercise Induced Dyspnea And Functional Capacity With Doppler-Derived Diastolic Function, Sumera Nasim, Najaf Nadeem, Aysha Zahidie, Tabbasum Sharif

Community Health Sciences

Background

Dyspnea is the frequent cause of exercise intolerance and physical inactivity among patients referred for exercise tolerance test. Diastolic dysfunction has shown significant correlation with exercise capacity and exercise induced dyspnea. To find out the frequency of diastolic dysfunction (DD) and the relationships between impaired exercise capacity and exercise induced dyspnea with DD by Doppler-derived indices among patients referred for stress test in a tertiary care hospital of Karachi.

Methods

For this study 135 consecutive patients who were referred for stress test at our non-invasive lab were screened for eligibility. Patients with valvular pathology, atrial fibrillation (AF) and coronary …

Infective Endocarditis In The U.S., 1998–2009: A Nationwide Study, David H. Bor, Steffie Woolhandler, Rachel Nardin, David Brusch, David U. Himmelstein

Publications and Research

Background
Previous studies based on local case series estimated the annual incidence of endocarditis in the U.S. at about 4 per 100,000 population. Small-scale studies elsewhere have reported similar incidence rates. However, no nationally-representative population-based studies have verified these estimates.

Methods and Findings
Using the 1998–2009 Nationwide Inpatient Sample, which provides diagnoses from about 8 million U.S. hospitalizations annually, we examined endocarditis hospitalizations, bacteriology, co-morbidities, outcomes and costs. Hospital admissions for endocarditis rose from 25,511 in 1998 to 38, 976 in 2009 (12.7 per 100,000 population in 2009). The age-adjusted endocarditis admission rate increased 2.4% annually. The proportion of patients …

Role Of Garlic Usage In Cardiovascular Disease Prevention: An Evidence-Based Approach, Waris Qidwai, Tabinda Ashfaq

Department of Family Medicine

Introduction:.Rapidly growing prevalence of cardiovascular disease is a major threat for the developed as well as developing world warranting urgent need of intervention. Complementary and alternative medicines are gaining popularity among general population because of their safety profile and easy administration. Garlic, in particular, is considered to be one of the best disease-preventive foods because of its potent and widespread effects. This study was done to find out the role of garlic usage in cardiovascular disease prevention.

Methodology : .Major databases including Google, PubMed,MEDLINE, and Cochrane library view were used for the literature search. Clinical trials conducted on humans assessing …

Molecular Mechanisms Related To Endotoxemia In Primary Human Cardiomyocytes In Culture, Atijah J. Collins

PCOM Biomedical Studies Student Scholarship

Cardiovascular disease (CVD) is the leading cause of death in the United States and has been for the past 80 years. Development of novel therapeutic agents to address the large number of CVD deaths requires an in depth understanding of the structural and functional properties of human cardiomyocytes. Over the last few years we have been developing an in vitro paradigm to assess molecular cardiodynamics in Primary Human Cardiomyocyte in culture (PHCC). We tested the hypothesis whether endotoxemia would exhibit a marked decrease in contractile proteins and cause apoptosis in PHCC. In the current series of experiments, we induced endotoxemia …

The Impairment Of Macrophage-To-Feces Reverse Cholesterol Transport During Inflammation Does Not Depend On Serum Amyloid A, Maria C. De Beer, Joanne M. Wroblewski, Victoria P. Noffsinger, Ailing Ji, Jason M. Meyer, Deneys R. Van Der Westhuyzen, Frederick C. De Beer, Nancy R. Webb

Saha Cardiovascular Research Center Faculty Publications

Studies suggest that inflammation impairs reverse cholesterol transport (RCT). We investigated whether serum amyloid A (SAA) contributes to this impairment using an established macrophage-to-feces RCT model. Wild-type (WT) mice and mice deficient in SAA1.1 and SAA2.1 (SAAKO) were injected intraperitoneally with ³H-cholesterol-labeled J774 macrophages 4 hr after administration of LPS or buffered saline. ³H-cholesterol in plasma 4 hr after macrophage injection was significantly reduced in both WT and SAAKO mice injected with LPS, but this was not associated with a reduced capacity of serum from LPS-injected mice to promote macrophage cholesterol efflux in vitro. Hepatic accumulation of ^{3 …}

Lipid Targets In Clinical Practice: Successes, Failures And Lessons To Be Learned, M Dunne, Oscar Mac Ananey, V Maher

Articles

Abstract

INTRODUCTION:

Optimal risk factor control is integral to managing patients with proven coronary heart disease (CHD+) and for those at risk of coronary heart disease (CHD-). The primary aim of the study was to assess the success rate of reaching lipid risk factor targets in a multiple risk factor clinic.

METHODS:

A retrospective audit was conducted in 488 patients (CHD+, n = 112; CHD-, n = 376) who attended the Cardiovascular Risk Factor Clinic at Tallaght Hospital, Dublin in 2009 and 2010.

RESULTS:

Risk factor targets achieved in CHD+ and CHD- patients were LDLc (54/62 %), HDLc (67/67 %), …

Is Dabigatran Superior To Warfarin In Treating Patients With Atrial Fibrillation?, Kelly Higgins

PCOM Physician Assistant Studies Student Scholarship

OBJECTIVE: The objective of this selective EBM review is to determine whether or not Dabigatran is superior to Warfarin in patients with atrial fibrillation.

STUDY DESIGN: Review of three English language primary studies published in 2007, 2009, and 2010.

DATA SOURCES: Three randomized control trials found using Cochrane Database.

OUTCOME(S) MEASURED: Outcomes measured were presence or absence of stroke or systolic embolism and intracranial hemorrhage. The absence of these events preserved neurologic function in patients with atrial fibrillation.

RESULTS: In both VKA-naïve and VKA-experienced patients, Dabigatran 150 mg was superior to Warfarin in both the prevention of stroke …

Interrupted Aortic Arch In The Adult, Amit Nanavati Md, Matthew W. Martinez, Nainesh Patel Md

Department of Medicine

No abstract provided.