Medical Specialties Commons^™

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

Dissertations and 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 …

Early Developmental Outcome In Children With Hypoplastic Left Heart Syndrome And Related Anomalies: The Single Ventricle Reconstruction Trial., Jane W. Newburger, Lynn A. Sleeper, David C. Bellinger, Caren S. Goldberg, Sarah Tabbutt, Minmin Lu, Kathleen A. Mussatto, Ismee A. Williams, Kathryn E. Gustafson, Seema Mital, Nancy Pike, Erica Sood, William T. Mahle, David S. Cooper, Carolyn Dunbar-Masterson, Catherine Dent Krawczeski, Alan Lewis, Shaji C. Menon, Victoria L. Pemberton, Chitra Ravishankar, Teresa W. Atz, Richard G. Ohye, J William Gaynor, Pediatric Heart Network Investigators, Girish S. Shirali

Manuscripts, Articles, Book Chapters and Other Papers

BACKGROUND: Survivors of the Norwood procedure may experience neurodevelopmental impairment. Clinical trials to improve outcomes have focused primarily on methods of vital organ support during cardiopulmonary bypass.

METHODS AND RESULTS: In the Single Ventricle Reconstruction trial of the Norwood procedure with modified Blalock-Taussig shunt versus right-ventricle-to-pulmonary-artery shunt, 14-month neurodevelopmental outcome was assessed by use of the Psychomotor Development Index (PDI) and Mental Development Index (MDI) of the Bayley Scales of Infant Development-II. We used multivariable regression to identify risk factors for adverse outcome. Among 373 transplant-free survivors, 321 (86%) returned at age 14.3 ± 1.1 (mean ± SD) months. Mean …

St Elevation: Telling Pathology From The Benign Patterns, Waleed Tallat Kayani, Henry D. Huang, Salman Bandeali, Salim S. Virani, James M. Wilson, Yochai Birnbaum

Office of the Provost

Benefits of early reperfusion in patients presenting with acute ST elevation myocardial infarction (STEMI) are well known. The American College of Cardiology / American Heart Association guidelines recommend triage decisions are made within 10 minutes of performing initial electrocardiogram (ECG). Since many patients presenting with ischemic symptoms may have ST elevation (STE) at baseline, not all STE signify transmural ischemia. Benign patterns can be easy to find in some cases. However, patients with benign STE at baseline (left ventricular hypertrophy, early repolarization pattern) may have ongoing ischemia and present with Non-ST elevation myocardial infarction (NSTEMI) or even STEMI superimposed on …

Ketamine As An Adjunct For The Long-Term Sedation And Analgesia Of A Patient With A Left Ventricular Assist Device (Lvad) And An Open Chest, Avni Gupta, Charles S. Kato, Eugene R. Viscusi

Department of Anesthesiology Faculty Papers

Conclusion:

A multimodal sedative and analgesic regimen that incorporates ketamine offers important therapeutic advantages in select patients who require very high doses of opioids and benzodiazepines, but warrants futher study.

Effect Of Obstructive Sleep Apnea On Mitral Valve Tenting., Gregg S. Pressman, Vincent M. Figueredo, Abel Romero-Corral, Ganesan Murali, Morris N Kotler

Division of Cardiology Faculty Papers

Obstructive apneas produce high negative intrathoracic pressure which imposes an afterload burden on the left ventricle. Such episodes might produce structural changes in the left ventricle over time. Doppler echocardiograms were obtained within 2 months of attended polysomnography. Patients were grouped according to apnea-hypopnea index (AHI): mild/no OSA (AHI < 15) and mod/severe OSA (AHI ≥ 15). Mitral valve tenting height and area, left ventricular (LV) long and short axis, and LV end-diastolic volume (LVEDV), were measured along with tissue Doppler parameters. Comparisons of measurements at baseline and follow up between and within groups were obtained; correlations between absolute changes (deltas) in echocardiographic parameters were also performed. After a mean follow up of 240 days mitral valve tenting height increased significantly (1.17 ± 0.12 cm to 1.28 ± 0.17 cm, p=0.001) in mod/severe OSA as did tenting area (2.30 ± 0.41 cm² to 2.66 ± 0.60 cm², p=0.0002); delta tenting height correlated with delta LVEDV (rho 0.43, p=0.01) and delta tenting area (rho 0.35, p=0.04). In mild/no OSA patients there was no significant change in tenting height; there was a borderline significant increase in tenting area (2.20 ± 0.44 cm …

Coronary Artery Bypass Grafting: Quality Of Life Of Patients In Karachi, Rozina Barolia, Fauziya Ali, Salma Jaffar

School of Nursing & Midwifery

In the Third World, cardiac Patients often suffer not only from the nature of their illnesses, but also the insufficiency of the facilities available. Although the effectiveness of coronary artery bypass grafting (CABG) is being evaluated in terms of mortality, complications or recurrence of symptoms, empirical studies assessing the change in Patients' quality of life (QOL) after CABG within the Pakistani cultural context are lacking.
Aims: The aims of the present study are to assess and compare the change in health-related quality of life before and 1 month after CABG and to assess the differences in QOL with respect to …

Hyperphosphorylation Of The Cardiac Ryanodine Receptor At Serine 2808 Is Not Involved In Cardiac Dysfunction After Myocardial Infarction., Hongyu Zhang, Catherine A Makarewich, Hajime Kubo, Wei Wang, Jason M Duran, Ying Li, Remus M Berretta, Walter J Koch, Xiongwen Chen, Erhe Gao, Héctor H Valdivia, Steven R Houser

Division of Cardiology Faculty Papers

RATIONALE: Abnormal behavior of the cardiac ryanodine receptor (RyR2) has been linked to cardiac arrhythmias and heart failure (HF) after myocardial infarction (MI). It has been proposed that protein kinase A (PKA) hyperphosphorylation of the RyR2 at a single residue, Ser-2808, is a critical mediator of RyR dysfunction, depressed cardiac performance, and HF after MI.

OBJECTIVE: We used a mouse model (RyRS2808A) in which PKA hyperphosphorylation of the RyR2 at Ser-2808 is prevented to determine whether loss of PKA phosphorylation at this site averts post MI cardiac pump dysfunction.

METHODS AND RESULTS: MI was induced in wild-type (WT) and S2808A …

Lpl Gene Variants Affect Apoc-Iii Response To Combination Therapy Of Statins And Fenofibric Acid In A Randomized Clinical Trial Of Individuals With Mixed Dyslipidemia, Ariel Brautbar, Salim S. Virani, John Belmont, Vijay Nambi, Peter H. Jones, Christie M. Ballantyne

Office of the Provost

ApoC-III is a proatherogenic protein associated with elevated triglycerides; its deficiency is associated with reduced atherosclerosis. Mixed dyslipidemia, characterized by elevated triglyceride and apoC-III levels and low HDL cholesterol level, with or without elevated LDL cholesterol, increases cardiovascular disease risk and is commonly treated with combined statin and fibrate therapy. We sought to identify single nucleotide polymorphisms (SNPs) associated with apoC-III level response to combination therapy with statins and fenofibric acid (FA) in individuals with mixed dyslipidemia. Participants (n = 1,250) in a multicenter, randomized, double-blind, active-controlled study examining response to FA alone and in combination with statin were genotyped …

Invited Commentary On: Orthotopic Heart Transplantation In Patients With Metabolic Risk Factors, Nicholas C. Cavarocchi, Paul Mather

Department of Surgery Faculty Papers

This is invited commentary to the following article:

Kilic, A., Conte, J. V., Shah, A. S., & Yuh, D. D. (2012). Orthotopic heart transplantation in patients with metabolic risk factors. Annals of Thoracic Surgery, 93(3), 718-724.

Relation Of Torsion And Myocardial Strains To Lv Ejection Fraction In Hypertension, Mustafa I. Ahmed Md, Ravi V. Desai Md, Krishna K. Gaddam Md, Bharath A. Venkatesh Phd, Shilpi Agarwal Ms, Md, Seidu Inusah Ms, Steven G. Lloyd Md, Thomas S. Denney Jr Phd, David Calhoun Md, Louis J. Dell'italia Md, Himanshu Gupta Md

Department of Medicine

No abstract provided.

Effects Of Preoperative Aspirin On Cardiocerebral And Renal Complications In Non-Emergent Cardiac Surgery Patients: A Sub-Group And Cohort Study., Longhui Cao, Scott Silvestry, Ning Zhao, James Diehl, Jianzhong Sun

Department of Anesthesiology Faculty Papers

BACKGROUND AND OBJECTIVE: Postoperative cardiocerebral and renal complications are a major threat for patients undergoing cardiac surgery. This study was aimed to examine the effect of preoperative aspirin use on patients undergoing cardiac surgery.

METHODS: An observational cohort study was performed on consecutive patients (n = 1879) receiving cardiac surgery at this institution. The patients excluded from the study were those with preoperative anticoagulants, unknown aspirin use, or underwent emergent cardiac surgery. Outcome events included were 30-day mortality, renal failure, readmission and a composite outcome - major adverse cardiocerebral events (MACE) that include permanent or transient stroke, coma, perioperative myocardial …

The Influence Of Antiretroviral Therapy On The Qtc Interval In An African Cohort, J. Shavadia, Reena Shah, Gerald Yonga, R. Patel, J. Stebbing, M. Nelson

Internal Medicine, East Africa

Cardiovascular disease in human immunodeficiency virus (HIV) infection encompasses a wide range of pathologic entities, including myocardial, pericardial, and endocardial disease, atherosclerosis, arrhythmias, and vasculitis. The most common manifestations of HIV-associated heart disease in sub- Saharan Africa are pericarditis, cardiomyopathy, and pulmonary hypertension [1]. Coronary artery disease, lipodystrophy, and metabolic syndrome, although common in developed countries, are traditionally thought to be less clinically significant problems in the African subcontinent [2]. It is well known that prolongation of the QTC interval can predispose patients to potentially fatal ventricular tachyarrhythmias, particularly torsades de pointes, and thus is an independent predictor of cardiovascular …

Improved Cardiac Management With A Disease Management Program Incorporating Comprehensive Lipid Profiling., John F Mcana, Neil I Goldfarb, Joseph Couto, Michelle A Henry, Gary Piefer, George M Rapier

College of Population Health Faculty Papers

The objective of this study was to evaluate the improved effectiveness of a disease management treatment protocol incorporating comprehensive lipid profiling and targeted lipid care based on lipid profile findings in patients with ischemic heart disease (IHD) or congestive heart failure (CHF) enrolled in a managed care plan. This retrospective cohort study, conducted over a 2-year period, compared outcomes between patients with a standard lipid profile to those evaluated with a comprehensive lipid profile. All adult members of the WellMed Medical Management, Inc. managed care health plan diagnosed with IHD or CHF, and continuously enrolled between July 1, 2006 and …

Direct Evidence For Inhibition Of Mitochondrial Permeability Transition Pore Opening By Sevoflurane Preconditioning In Cardiomyocytes: Comparison With Cyclosporine A., Anna Onishi, Masami Miyamae, Kazuhiro Kaneda, Junichiro Kotani, Vincent M. Figueredo

Division of Cardiology Faculty Papers

To assess whether sevoflurane preconditioning is associated with inhibition of mitochondrial permeability transition pore (MPTP), the effects of sevoflurane were compared with those of cyclosporine A, a known inhibitor of MPTP opening. Isolated perfused guinea pig hearts underwent 30 min global ischemia and 120 min reperfusion (control). Sevoflurane preconditioning was elicited by administration of 2% sevoflurane for 10 min with 10 min washout before ischemia (sevoflurane). A preconditioning-like cardioprotection was also induced by administering cyclosporine A (0.2 μM) for 15 min, starting 5 min before ischemia and for 10 min after the onset of reperfusion (cyclosporine A). Left ventricular developed …

Feasibility And Compliance With Daily Home Ecg Monitoring Of The Qt Interval In Heart Transplant Recipients, Erik V. Carter, Kathleen T. Hickey, David M. Pickham, Lynn V. Doering, Belinda Chen, Patricia R. E. Harris, Barbara J. Drew

Collected Faculty Scholarship

About 13% of adult heart transplant recipients do not survive to one year and a major cause of death is acute cellular allograft rejection.^1,2 According to the 2009 annual United States data published from the International Society for Heart Lung Transplantation Registry, acute rejection occurs in 25 – 35% of transplant recipients within the first year following transplant surgery.³ In order to detect the early stages of rejection so that more aggressive and early immunosuppressant therapy can be initiated, frequent biopsies of heart tissue are performed (typically, weekly or every other week in the first 3 months and …

Hypertension In A Young Boy: An Energy Drink Effect, Asma Usman, Ambreen Jawaid

Department of Family Medicine

Background: Use of energy drinks has significantly increased in recent times. Besides athletes, teenagers and students are among the most common consumers. However, popularity is also increasing among the younger and older age groups. Most of the users believe that they are a good source of instant energy and are unaware of its high Caffeine content resulting in harmful effects on health.Case Presentation: We report the case of a young boy who presented with palpitations and high blood pressure as a result of energy drinks usage. He had been consuming a "Sting" energy drink on regular basis while studying …

Trends In Hospital Admissions For Myocardial Infarcts For Women In Arizona, Florida And Maryland In 2000 To 2010, Rebecca Farmer Mcintyre

MUSC Theses and Dissertations

Coronary arterial disease is the leading cause of death and morbidity in developing countries. Acute myocardial infarction (AMI) has traditionally been considered a disease affecting mostly men, yet women are increasingly at risk due to obesity and diabetes. However, current trends in the AMI risk for women are not well understood. This study used archival data on hospital discharges from three states within the USA to examine the 10-year trend in presentations of patients to emergency rooms (ER) with a presenting diagnosis of chest pain and AMI, to document rate changes by gender over time. We observed a decreasing number …

The Influence Of The Method Of Cerebral Protection During Neonatal Cardiac Surgery On The Development Of Attention Deficit/Hyperactivity Disorder, Joseph J. Sistino

MUSC Theses and Dissertations

Complex congenital heart disease is a common birth defect requiring surgery soon after birth. Surgery can use a complete interruption of cerebral blood flow (DHCA) or it can be performed using regional low flow perfusion (RLFP). Either approach places the neonate at risk for oxygen deprivation resulting in neurodevelopmental impairment and Attention Deficit/Hyperactivity Disorder (ADHD). RLFP has been widely adopted but its effect on ADHD has not been elucidated. We extracted surgical records data and surveyed parents of 5-16 year old children who had neonatal surgery using DHCA or RLFP in 1995-2006 to determine the prevalence of ADHD after DHCA …

Spontaneous Coronary Artery Dissection: A Rare But Deadly Cause Of Acs In Younger Patients, Daniel J. Makowski Do, David A. Cox Md

Department of Medicine

No abstract provided.

Imaging And Intervention For Coronary Artery Disease Following Irradiation Of Malignant Thymoma, Saulat H. Fatimi, Salima Ahmed Bhimani, Ranish Deedar-Ali- Khawaja, Ali Khawaja

Section of Cardiothoracic Surgery

Thymomas are rare malignant epithelial growths, constituting 20% of mediastinal tumours. Resection followed by irradiation may be employed in all thymomas except for stage 1 thymomas. Mediastinal irradiation is associated with coronary artery disease. The mean duration of presentation of post-irradiation coronary artery disease is 16 years (range 3-29 years). In our patient coronary artery disease was found only a year post irradiation. A 55 year old male who presented with complaints of dyspnoea, retrosternal chest pain and heaviness since one year underwent resection for malignant thymoma followed by radiotherapy. He presented with coronary artery disease a year after undergoing …

Role Of The Immune System And Bioactive Lipids In Trafficking Bone Marrow-Derived Stem Cells In Patients With Ischemic Heart Disease, Ahmed Abdel-Latif

Theses and Dissertations--Microbiology, Immunology, and Molecular Genetics

Acute myocardial infarction (AMI) triggers the mobilization of stem/progenitor cells from bone marrow (BMSPCs) into peripheral blood (PB). The underlying mechanisms orchestrating this mobilization and subsequent homing of BMSPCs to the myocardium are poorly understood. While the role of traditional chemokines in the mobilization and homing of hematopoietic stem cell (HSCs) to BM niches is undisputed, their role in directing BMSPCs to the highly proteolytic environment of the ischemic myocardium is debatable and other redundant mechanism may exist. Based on our observation that bioactive lipids, such as sphingosine-1 phosphate (S1P) and ceramide-1 phosphate (C1P), play an important role in regulating …

Infectious Intracranial Aneurysms: Collaboration For Treatment Success, Erin M. Conahan Rn, Bsn, Cnrn

Patient Care Services / Nursing

No abstract provided.

How Vats Has Changed The Management Of Spontaneous Pneumothorax In The 21st Century, Saulat H. Fatimi, Hashim Muhammad Hanif, Sana Mansoor, Marium Muzaffar

Section of Cardiothoracic Surgery

Objective: To determine the outcome of patients having undergone Video Assisted Thoracoscopic Surgery (VATS) for spontaneous pneumothrox in terms of hospital stay, complications and recurrence.
Methods: The netrospective study included the review of 39 cases who had presented with spontaneous pneumothorax at the Aga Khan University Hospital, Karachi, Pakistan, between January 2001 to November 2008 and had undergone video assisted thoracoscopic surgery (VATS).
Results: The duration of hospital stay (had a range of 3 to 9 days), and the length of chest tube in place (a range of 2 to 8 days), 2 (5.1%) patients developed recurrence after VATS while …

Subclavian Steal Syndrome Secondary To Subclavian Artery Thrombosis In A Patient With Homocysteinemia And Its Successful Treatment, Marium Muzaffar, Hashim Muhammed Hanif, Saulat H. Fatimi, M. Tariq

Section of Cardiothoracic Surgery

Subclavian steal syndrome (SSS) is a rare condition. It results from subclavian artery (SA) stenosis proximal to the origin of the vertebral artery. It is characterized by cerebral ischaemia with associated symptoms of vertebrobasilar hypoperfusion and/or symptoms of brainstem or arm ischaemia. We describe a case of a 35 year old male who presented with persistent vertigo for two months, blue discoloration and pain in the left fingers for two weeks. A diagnosis of SSS was made and patient was treated with a gortex graft from the arch of the aorta to the second portion of the left subclavian artery. …

Cardioprotection Of Controlled And Cardiac-Specific Over-Expression Of A(2a)-Adenosine Receptor In The Pressure Overload., Eman A Hamad, Weizhong Zhu, Tung O Chan, Valerie Myers, Erhe Gao, Xue Li, Jin Zhang, Jianliang Song, Xue-Qian Zhang, Joseph Y Cheung, Walter Koch, Arthur M Feldman

Center for Translational Medicine Faculty Papers

Adenosine binds to three G protein-coupled receptors (R) located on the cardiomyocyte (A(1)-R, A(2A)-R and A(3)-R) and provides cardiac protection during both ischemic and load-induced stress. While the role of adenosine receptor-subtypes has been well defined in the setting of ischemia-reperfusion, far less is known regarding their roles in protecting the heart during other forms of cardiac stress. Because of its ability to increase cardiac contractility and heart rate, we hypothesized that enhanced signaling through A(2A)-R would protect the heart during the stress of transverse aortic constriction (TAC). Using a cardiac-specific and inducible promoter, we selectively over-expressed A(2A)-R in FVB …

Orphan Nuclear Receptor Nur77 Regulates Androgen Receptor Gene Expression In Mouse Ovary., Anyi Dai, Guijun Yan, Qinyuan He, Yue Jiang, Qun Zhang, Ting Fang, Lijun Ding, Jianxin Sun, Haixiang Sun, Yali Hu

Center for Translational Medicine Faculty Papers

The androgen receptor (AR) is a nuclear receptor that is expressed in growing follicles and involved in folliculogenesis and follicle growth. The orphan nuclear receptor, Nur77, also has an important role in steroid signaling and follicle maturation. We hypothesized that AR levels and androgen signaling through AR are regulated by Nur77 in the ovary. In the ovaries of Nur77 knockout mice (n = 5), real-time PCR results showed that the mRNA levels of AR and an androgen signaling target gene, Kitl, were decreased by 35% and 24%, respectively, relative to wild-type mice (n = 5), which suggested transcriptional regulation of …

Microrna-145 Protects Cardiomyocytes Against Hydrogen Peroxide (H₂O₂)-Induced Apoptosis Through Targeting The Mitochondria Apoptotic Pathway., Ruotian Li, Guijun Yan, Qiaoling Li, Haixiang Sun, Yali Hu, Jianxin Sun, Biao Xu

Center for Translational Medicine Faculty Papers

MicroRNAs, a class of small and non-encoding RNAs that transcriptionally or post-transcriptionally modulate the expression of their target genes, has been implicated as critical regulatory molecules in many cardiovascular diseases, including ischemia/reperfusion induced cardiac injury. Here, we report microRNA-145, a tumor suppressor miRNA, can protect cardiomyocytes from hydrogen peroxide H₂O₂-induced apoptosis through targeting the mitochondrial pathway. Quantitative real-time PCR (qPCR) demonstrated that the expression of miR-145 in either ischemia/reperfused mice myocardial tissues or H₂O₂-treated neonatal rat ventricle myocytes (NRVMs) was markedly down-regulated. Over-expression of miR-145 significantly inhibited the H₂O₂-induced cellular apoptosis, ROS production, mitochondrial structure disruption as well as the …

Ectopic And Atretic Ostium Of Left Main Coronary Artery: From Interleaflet Triangle Between Left And Noncoronary Cusps, Ta-Chung Shen, Hsin-Hua Chou, Kuei-Ton Tsai

The Texas Heart Institute Journal

Left main coronary artery atresia is an extremely rare coronary anomaly in which there is no left coronary ostium and the left main trunk ends blindly. Ectopic origin of the left coronary artery from the left ventricle is an even rarer condition. Herein, we describe the case of a 37-year-old woman whose left main coronary artery atresia was not corrected during previous surgical correction of patent ductus arteriosus and aortic insufficiency. Five years after that first operation, the patient developed severe angina and heart failure. She underwent coronary artery bypass grafting with greater saphenous vein directly to the left main …

Bioabsorbable Atrial Septal Occluder For Percutaneous Closure Of Atrial Septal Defect In Children, Osman Baspinar, Mehmet Kervancioglu, Metin Kilinc, Ahmet Irdem

The Texas Heart Institute Journal

The BioSTAR bioabsorbable septal repair implant is a new transcatheter secundum atrial septal defect occlusion device that is absorbed and replaced by healthy native tissue. This retrospective analysis was designed to determine the most significant factors for its successful use in children. From October 2009 through December 2010, 33 children underwent catheterization to close secundum atrial septal defects by means of the BioSTAR. The mean age of the patients was 6.8 ± 3.4 years (range, 2.5-13 yr), and the mean body weight was 22.6 ± 11 kg (range, 11-55 kg). The device was successfully implanted in 91% of patients (30/33). …

After Avandia: The Use Of Antidiabetic Drugs In Patients With Heart Failure, Khaled I Khalaf, Heinrich Taegtmeyer

The Texas Heart Institute Journal

Managing diabetes mellitus is an ongoing concern, especially in the presence of heart failure. Recent reports have drawn attention to adverse cardiovascular events associated with the use of thiazolidinediones, including rosiglitazone (Avandia). In 2011, the U.S. Food and Drug Administration implemented a stringent “restricted access program” for the prescription of Avandia. Other studies, which have revealed increased mortality rates in association with tight glycemic control, raise serious concerns about managing diabetes in heart-failure patients.

Herein, we provide a perspective on the management of noninsulin-dependent diabetes in patients with heart failure. We point out that thiazolidinediones exert their major effects through …