Diseases Commons^™

Head-To-Head Comparison Of Relevant Cell Sources Of Small Extracellular Vesicles For Cardiac Repair: Superiority Of Embryonic Stem Cells, Hernán González-King, Patricia G Rodrigues, Tamsin Albery, Benyapa Tangruksa, Ramya Gurrapu, Andreia M Silva, Gentian Musa, Dominika Kardasz, Kai Liu, Bengt Kull, Karin Åvall, Katarina Rydén-Markinhuhta, Tania Incitti, Nitin Sharma, Cecilia Graneli, Hadi Valadi, Kasparas Petkevicius, Miguel Carracedo, Sandra Tejedor, Alena Ivanova, Sepideh Heydarkhan-Hagvall, Phillipe Menasché, Jane Synnergren, Niek Dekker, Qing-Dong Wang, Karin Jennbacken

Journal Articles

Small extracellular vesicles (sEV) derived from various cell sources have been demonstrated to enhance cardiac function in preclinical models of myocardial infarction (MI). The aim of this study was to compare different sources of sEV for cardiac repair and determine the most effective one, which nowadays remains limited. We comprehensively assessed the efficacy of sEV obtained from human primary bone marrow mesenchymal stromal cells (BM-MSC), human immortalized MSC (hTERT-MSC), human embryonic stem cells (ESC), ESC-derived cardiac progenitor cells (CPC), human ESC-derived cardiomyocytes (CM), and human primary ventricular cardiac fibroblasts (VCF), in in vitro models of cardiac repair. ESC-derived sEV (ESC-sEV) …

Effect Of Flecainide And Ibutilide Alone And In Combination To Terminate And Prevent Recurrence Of Atrial Fibrillation, Alexander Burashnikov, José M. Di Diego, Bence Patocskai, Debra S. Echt, Luiz Belardinelli, Charles Antzelevitch

Division of Cardiology Faculty Papers

BACKGROUND: There is a need for improved approaches to rhythm control therapy of atrial fibrillation (AF).

METHODS: The effectiveness of flecainide (1.5 µmol/L) and ibutilide (20 nmol/L), alone and in combination, to cardiovert and prevent AF recurrence was studied in canine-isolated coronary-perfused right atrioventricular preparations. We also examined the safety of the combination of flecainide (1.5 µmol/L) and ibutilide (50 nmol/L) using canine left ventricular wedge preparations.

RESULTS: Sustained AF (>1 hour) was inducible in 100%, 60%, 20%, and 0% of atria in the presence of acetylcholine alone, acetylcholine+ibutilide, acetylcholine+flecainide, and acetylcholine+ibutilide+flecainide, respectively. When used alone, flecainide and ibutilide …

Interplay Of Hypoxia-Inducible Factors And Oxygen Therapy In Cardiovascular Medicine, Yafen Liang, Wei Ruan, Yandong Jiang, Richard Smalling, Xiaoyi Yuan, Holger K Eltzschig

Journal Articles

Mammals have evolved to adapt to differences in oxygen availability. Although systemic oxygen homeostasis relies on respiratory and circulatory responses, cellular adaptation to hypoxia involves the transcription factor hypoxia-inducible factor (HIF). Given that many cardiovascular diseases involve some degree of systemic or local tissue hypoxia, oxygen therapy has been used liberally over many decades for the treatment of cardiovascular disorders. However, preclinical research has revealed the detrimental effects of excessive use of oxygen therapy, including the generation of toxic oxygen radicals or attenuation of endogenous protection by HIFs. In addition, investigators in clinical trials conducted in the past decade have …

Prolylcarboxypeptidase Alleviates Hypertensive Cardiac Remodeling By Regulating Myocardial Tissue Angiotensin Ii, Binh Y Nguyen, Fangchao Zhou, Pablo Binder, Wei Liu, Susanne S Hille, Xiaojing Luo, Min Zi, Hongyuan Zhang, Antony Adamson, Fozia Z Ahmed, Sam Butterworth, Elizabeth J Cartwright, Oliver J Müller, Kaomei Guan, Elizabeth M Fitzgerald, Xin Wang

Journal Articles

Background Prolonged activation of angiotensin II is the main mediator that contributes to the development of heart diseases, so converting angiotensin II into angiotensin 1-7 has emerged as a new strategy to attenuate detrimental effects of angiotensin II. Prolylcarboxypeptidase is a lysosomal pro-X carboxypeptidase that is able to cleave angiotensin II at a preferential acidic pH optimum. However, insufficient attention has been given to the cardioprotective functions of prolylcarboxylpeptidase. Methods and Results We established a CRISPR/CRISPR-associated protein 9-mediated global prolylcarboxylpeptidase-knockout and adeno-associated virus serotype 9-mediated cardiac prolylcarboxylpeptidase overexpression mouse models, which were challenged with the angiotensin II infusion (2 mg/kg …

Targeting Myocardial Equilibrative Nucleoside Transporter Ent1 Provides Cardioprotection By Enhancing Myeloid Adora2b Signaling, Wei Ruan, Jiwen Li, Seungwon Choi, Xinxin Ma, Yafen Liang, Ragini Nair, Xiaoyi Yuan, Tingting W Mills, Holger K Eltzschig

Journal Articles

Previous studies implicate extracellular adenosine signaling in attenuating myocardial ischemia and reperfusion injury (IRI). This extracellular adenosine signaling is terminated by its uptake into cells by equilibrative nucleoside transporters (ENTs). Thus, we hypothesized that targeting ENTs would function to increase cardiac adenosine signaling and concomitant cardioprotection against IRI. Mice were exposed to myocardial ischemia and reperfusion injury. Myocardial injury was attenuated in mice treated with the nonspecific ENT inhibitor dipyridamole. A comparison of mice with global Ent1 or Ent2 deletion showed cardioprotection only in Ent1-/- mice. Moreover, studies with tissue-specific Ent deletion revealed that mice with myocyte-specific Ent1 deletion (Ent1loxP/loxP …

Anesthesia For Echocardiography And Magnetic Resonance Imaging In The African Clawed Frog (Xenopus Laevis), Antonio F Corno, Noelia E Flores, Wen Li, Thomas H Gomez, Jorge D Salazar

Journal Articles

This report describes an anesthesia technique that we used to study cardiovascular anatomy and physiology with echocardiography and cardiac magnetic resonance (CMR) in 46 African clawed frogs (Xenopus laevis) (n = 24 for electrocardiography and n = 22 for CMR). For administration of anesthesia, 3 holding tanks, one each for transportation, sedation, and recovery, were filled with filtered water, with 0.05% buffered tricaine methasulfonate solution (MS-222) added into the sedation tank. Fifteen minutes after the frog was placed in the sedation tank, a paper towel was soaked in MS-222 solution, and the frog was placed in a …

Sirpα Mediates Igf1 Receptor In Cardiomyopathy Induced By Chronic Kidney Disease, Sandhya S Thomas, Jiao Wu, Giovanni Davogustto, Michael W Holliday, Kristin Eckel-Mahan, Daniela Verzola, Giacomo Garibotto, Zhaoyong Hu, William E Mitch, Heinrich Taegtmeyer

Journal Articles

BACKGROUND: Chronic kidney disease (CKD) is characterized by increased myocardial mass despite near-normal blood pressure, suggesting the presence of a separate trigger. A potential driver is SIRPα (signal regulatory protein alpha)-a mediator impairing insulin signaling. The objective of this study is to assess the role of circulating SIRPα in CKD-induced adverse cardiac remodeling.

METHODS: SIRPα expression was evaluated in mouse models and patients with CKD. Specifically, mutant, muscle-specific, or cardiac muscle-specific SIRPα KO (knockout) mice were examined after subtotal nephrectomy. Cardiac function was assessed by echocardiography. Metabolic responses were confirmed in cultured muscle cells or cardiomyocytes.

RESULTS: We demonstrate that …

Prolonged Cardiac Nr4a2 Activation Causes Dilated Cardiomyopathy In Mice, Sadia Ashraf, Heinrich Taegtmeyer, Romain Harmancey

Journal Articles

Transcription factors play a fundamental role in cardiovascular adaptation to stress. Nuclear receptor subfamily 4 group A member 2 (NR4A2; NURR1) is an immediate-early gene and transcription factor with a versatile role throughout many organs. In the adult mammalian heart, and particularly in cardiac myocytes, NR4A2 is strongly up-regulated in response to beta-adrenergic stimulation. The physiologic implications of this increase remain unknown. In this study, we aimed to interrogate the consequences of cardiac NR4A2 up-regulation under normal conditions and in response to pressure overload. In mice, tamoxifen-dependent, cardiomyocyte-restricted overexpression of NR4A2 led to cardiomyocyte hypertrophy, left ventricular dilation, heart failure, …

Ucp3 (Uncoupling Protein 3) Insufficiency Exacerbates Left Ventricular Diastolic Dysfunction During Angiotensin Ii-Induced Hypertension, Xu Chen, Sadia Ashraf, Nadia Ashraf, Romain Harmancey

Journal Articles

Background Left ventricular diastolic dysfunction, an early stage in the pathogenesis of heart failure with preserved ejection fraction, is exacerbated by joint exposure to hypertension and obesity; however, the molecular mechanisms involved remain uncertain. The mitochondrial UCP3 (uncoupling protein 3) is downregulated in the heart with obesity. Here, we used a rat model of UCP3 haploinsufficiency (ucp3

Alcohol Ablation Of Cardiac Tissues Quantified And Evaluated Using Cielab Euclidean Distances, Ashley Rook, Mathews M John, Allison Post, Mehdi Razavi

The Texas Heart Institute Journal

Ethanol solubilizes cell membranes, making it useful for various ablation applications. We examined the effect of time and alcohol type on the extent of ablation, quantified as Euclidean distances between color coordinates. We obtained biopsy punch samples (diameter, 6 mm) of left atrial appendage, atrial, ventricular, and septal tissue from porcine hearts and placed them in transwell plates filled with ethanol or methanol for 10, 20, 30, 40, 50, or 60 min. Control samples were taken for each time point. At each time point, samples were collected, cut transversely, and photographed. With use of a custom MATLAB program, all images …

Dietary Fat And Sugar Differentially Affect Β-Adrenergic Stimulation Of Cardiac Erk And Akt Pathways In C57bl/6 Male Mice Subjected To High-Calorie Feeding, Sadia Ashraf, Gizem Yilmaz, Xu Chen, Romain Harmancey

Journal Articles

BACKGROUND: High dietary fat and sugar promote cardiac hypertrophy independently from an increase in blood pressure. The respective contribution that each macronutrient exerts on cardiac growth signaling pathways remains unclear.

OBJECTIVE: The goal of this study was to investigate the mechanisms by which high amounts of dietary fat and sugar affect cardiac growth regulatory pathways.

METHODS: Male C57BL/6 mice (9 wk old; n = 20/group) were fed a standard rodent diet (STD; kcal% protein-fat-carbohydrate, 29-17-54), a high-fat diet (HFD; 20-60-20), a high-fat and high-sugar Western diet (WD; 20-45-35), a high-sugar diet with mixed carbohydrates (HCD; 20-10-70), or a high-sucrose diet …

The Future Of Tissue Engineering In Heart Transplantation, Doris A Taylor

The Texas Heart Institute Journal

No abstract provided.

Targeting Hepatic Heparin-Binding Egf-Like Growth Factor (Hb-Egf) Induces Anti-Hyperlipidemia Leading To Reduction Of Angiotensin Ii-Induced Aneurysm Development, Seonwook Kim, Lihua Yang, Seongu Kim, Richard G. Lee, Mark J. Graham, Judith A. Berliner, Aldons J. Lusis, Lei Cai, Ryan E. Temel, Debra L. Rateri, Sangderk Lee

Saha Cardiovascular Research Center Faculty Publications

Objective

The upregulated expression of heparin binding EGF-like growth factor (HB-EGF) in the vessel and circulation is associated with risk of cardiovascular disease. In this study, we tested the effects of HB-EGF targeting using HB-EGF-specific antisense oligonucleotide (ASO) on the development of aortic aneurysm in a mouse aneurysm model.

Approach and results

Low-density lipoprotein receptor (LDLR) deficient mice (male, 16 weeks of age) were injected with control and HB-EGF ASOs for 10 weeks. To induce aneurysm, the mice were fed a high fat diet (22% fat, 0.2% cholesterol; w/w) at 5 week point of ASO administration and infused with angiotensin …

Comparative Efficacy Of Nebivolol And Metoprolol To Prevent Tachycardia-Induced Cardiomyopathy In A Porcine Model, Alireza Nazeri, Macarthur A Elayda, Ana Maria Segura, Raymond F Stainback, Joanna Nathan, Vei-Vei Lee, Christina Bove, Luiz Sampaio, Brian Grace, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Chronic tachycardia is a well-known cause of nonischemic cardiomyopathy. We hypothesized that nebivolol, a β-blocker with nitric oxide activity, would be superior to a pure β-blocker in preventing tachycardia-induced cardiomyopathy in a porcine model.

Fifteen healthy Yucatan pigs were randomly assigned to receive nebivolol, metoprolol, or placebo once a day. All pigs underwent dual-chamber pacemaker implantation. The medication was started the day after the pacemaker implantation. On day 7 after implantation, each pacemaker was set at atrioventricular pace (rate, 170 beats/min), and the pigs were observed for another 7 weeks. Transthoracic echocardiograms, serum catecholamine levels, and blood chemistry data were …

The Mosaic Mitral Valve Bioprosthesis: A Long-Term Clinical And Hemodynamic Follow-Up, Michele Celiento, Stefania Blasi, Andrea De Martino, Stefano Pratali, Aldo D Milano, Uberto Bortolotti

The Texas Heart Institute Journal

We reviewed the cases of 100 patients (mean age, 73 ± 10 yr; 64 men) who had mitral valve replacement with a Medtronic Mosaic porcine bioprosthesis from 1995 through 2011. The mean New York Heart Association (NYHA) class was 3 ± 0.7, and 52 patients were in atrial fibrillation. Prosthetic sizes were chiefly 27 mm (50 patients) and 29 mm (40 patients). Follow-up ended in December 2012 and is 97% complete, with a cumulative duration of 611 patient-years (mean duration, 6 ± 4.6 yr; maximum, 17.7 yr). The early mortality rate was 10% (6% in elective patients); late deaths occurred …

Ultrasound Biomicroscopic Imaging For Interleukin-1 Receptor Antagonist-Inhibiting Atherosclerosis And Markers Of Inflammation In Atherosclerotic Development In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Yan Sun, Qin Wang, Jiao Yang, Ya Yang, Li Song, Zheng Wang, Xiang-Hong Luo, Rui-Juan Su

The Texas Heart Institute Journal

We sought to validate the hypothesis that the development of atherosclerosis can be suppressed by the interleukin-1 receptor antagonist (IL-1Ra) in murine models of atherosclerosis in vivo, noninvasively seen by means of high-resolution ultrasound biomicroscopy, and we studied changes in inflammatory markers such as IL-1 and C-reactive protein (CRP) plasma levels in these models of atherosclerosis.

We divided IL-1Ra+/−/apolipoprotein-E (apoE)−/− and IL-1Ra+/+/apoE−/− mice into 2 age groups, used as atherosclerotic models. The control groups were age-matched IL-1Ra+/+/apoE+/+ mice. Plaque thickness was measured in the ascending aorta in short-axis images by means of ultrasound and histology. Plasma levels of IL-1 and …

Scarnas Regulate Splicing And Vertebrate Heart Development., Prakash Patil, Nataliya Kibiryeva, Tamayo Uechi, Jennifer A. Marshall, James E. O'Brien, Michael Artman, Naoya Kenmochi, Douglas C. Bittel

Manuscripts, Articles, Book Chapters and Other Papers

Alternative splicing (AS) plays an important role in regulating mammalian heart development, but a link between misregulated splicing and congenital heart defects (CHDs) has not been shown. We reported that more than 50% of genes associated with heart development were alternatively spliced in the right ventricle (RV) of infants with tetralogy of Fallot (TOF). Moreover, there was a significant decrease in the level of 12 small cajal body-specific RNAs (scaRNAs) that direct the biochemical modification of specific nucleotides in spliceosomal RNAs. We sought to determine if scaRNA levels influence patterns of AS and heart development. We used primary cells derived …

Is Autologous Or Heterologous Pericardium Better For Valvuloplasty? A Comparative Study Of Calcification Propensity, Wen-Jian Jiang, Yong-Chao Cui, Jin-Hua Li, Xiu-Hui Zhang, Huan-Huan Ding, Yong-Qiang Lai, Hong-Jia Zhang

The Texas Heart Institute Journal

Pericardial calcification is detrimental to the long-term durability of valvuloplasty. However, whether calcification susceptibility differs between heterologous and autologous pericardium is unclear. In this study, we compared the progression of calcification in vivo between autologous and heterologous pericardium.

We randomly divided 28 rabbits into 4 equal groups. Resected rabbit pericardium served as autologous pericardium, and commercial bovine pericardium served as heterologous pericardium. We subcutaneously embedded one of each pericardial patch in the abdominal walls of 21 of the rabbits. The 7 control rabbits (group A) received no implants. The embedded samples were removed at 2 months in group B, at …

Pathways Involved In Interleukin-1Β-Mediated Murine Cardiomyocyte Apoptosis., Yi Shen, Jie Qin, Peili Bu

The Texas Heart Institute Journal

Accumulating evidence suggests that interleukin-1 (IL-1) signaling plays an essential role in the pathogenesis of heart failure by inducing cardiomyocyte apoptosis, but the mechanisms of this process are poorly defined. We further explored these molecular pathways.

We isolated cardiomyocytes from neonatal mice and then cultured and stimulated them with murine IL-1β in vitro. Cell apoptotic ratios were measured by means of flow cytometry. Expression of effector molecules was analyzed by means of enzyme-linked immunosorbent assay, Western blotting, and real-time quantitative polymerase chain reaction. The results showed that IL-1β induced murine cardiomyocyte apoptosis through a release of cytochrome c into cytoplasm …

Cardiac Fibroblast-Dependent Extracellular Matrix Accumulation Is Associated With Diastolic Stiffness In Type 2 Diabetes., Kirk R. Hutchinson, C. Kevin Lord, T. Aaron West, James A. Stewart

College of Arts and Sciences Publications and Scholarship

Cardiovascular complications are a leading cause of death in patients with type 2 diabetes mellitus (T2DM). Diastolic dysfunction is one of the earliest manifestations of diabetes-induced changes in left ventricular (LV) function, and results from a reduced rate of relaxation and increased stiffness. The mechanisms responsible for increased stiffness are not completely understood. Chronic hyperglycemia, advanced glycation endproducts (AGEs), and increased levels of proinflammatory and profibrotic cytokines are molecular pathways known to be involved in regulating extracellular matrix (ECM) synthesis and accumulation resulting in increased LV diastolic stiffness. Experiments were conducted using a genetically-induced mouse model of T2DM generated by …

Some Thoughts About The Historic Events That Led To The First Clinical Implantation Of A Total Artificial Heart, Denton A Cooley

The Texas Heart Institute Journal

No abstract provided.

Early Hemodynamic And Biochemical Changes In Overloaded Swine Ventricle.Early Hemodynamic And Biochemical Changes In Overloaded Swine Ventricle, Sandro Gelsomino, Fabiana Lucà, Chiara Nediani, Sandra Zecchi Orlandini, Daniele Bani, Antonio S Rubino, Attilio Renzulli, Roberto Lorusso, Andrea Consolo, Antonino Lo Cascio, Jos Maessen, Gian Franco Gensini

The Texas Heart Institute Journal

The present study was undertaken to investigate, in an animal model, the relationship between sarcoplasmic reticulum Ca2+-ATPase (SERCA2a) activity, phospholamban phosphorylation, acylphosphatase activity, and hemodynamic changes that occur in the early phase of pressure overload. In 54 study-group pigs, weighing 40±5 kg each, an aortic stenosis was created with a band of umbilical tape tied around the aorta; 18 sham-operated pigs formed our control group. Eight animals (6 study and 2 control) were randomly assigned to each experimental time (0.5, 3, 6, 12, 24, 48, 72, 96, and 168 hr). All indices of left ventricular function declined significantly, with a …

Induction Of Early Biomarkers In A Thrombus-Induced Sheep Model Of Ischemic Heart Failure, Aluganti N Chandrakala, Pawel Kwiatkowski, Chittoor B Sai-Sudhakar, Benjamin Sun, Angela Phillips, Sampath Parthasarathy

The Texas Heart Institute Journal

The levels of brain natriuretic peptide (BNP) and monocyte chemoattractant protein-1 (MCP-1) are known to be increased in the sera of subjects with heart failure. Existing models do not account for the biomass of thrombus that occurs in patients undergoing myocardial infarction. In this study, we compared the expressions of sheep-derived genes for BNP, MCP-1, and atrial natriuretic peptide in a new large-animal model of thrombus-induced heart failure. Thrombus of autologous platelets was injected directly into the left circumflex coronary arteries of sheep. Cardiac ischemic injury was evaluated by troponin I levels, and heart failure progression was monitored with the …

Mitochondrial Cardiomyopathy: Pathophysiology, Diagnosis, And Management, Deborah E Meyers, Haseeb Ilias Basha, Mary Kay Koenig

The Texas Heart Institute Journal

Mitochondrial disease is a heterogeneous group of multisystemic diseases that develop consequent to mutations in nuclear or mitochondrial DNA. The prevalence of inherited mitochondrial disease has been estimated to be greater than 1 in 5,000 births; however, the diagnosis and treatment of this disease are not taught in most adult-cardiology curricula. Because mitochondrial diseases often occur as a syndrome with resultant multiorgan dysfunction, they might not immediately appear to be specific to the cardiovascular system. Mitochondrial cardiomyopathy can be described as a myocardial condition characterized by abnormal heart-muscle structure, function, or both, secondary to genetic defects involving the mitochondrial respiratory …

The Pathobiology Of Acute Coronary Syndromes: Clinical Implications And Central Role Of The Mitochondria, L Maximilian Buja

The Texas Heart Institute Journal

Ongoing investigation has provided new insights into the pathobiology of myocardial ischemic injury. These include an improved understanding of the roles of the major modes of cell injury and death, including oncosis, apoptosis, and unregulated autophagy, as well as the central role of the mitochondria in the progression of myocardial ischemic injury, reperfusion injury, and myocardial conditioning. This understanding is providing insights for developing new pathophysiologic, pharmacologic, and cell-based therapies, alone or in combination with percutaneous coronary interventions, for better preservation of myocardium and reduction of morbidity and mortality rates from ischemic heart disease.

Cellular Retrograde Cardiomyoplasty And Relaxin Therapy For Postischemic Myocardial Repair In A Rat Model, Gabriella Di Lascio, Guy Harmelin, Mattia Targetti, Cristina Nanni, Giacomo Bianchi, Tommaso Gasbarri, Sandro Gelsomino, Daniele Bani, Sandra Zecchi Orlandini, Massimo Bonacchi

The Texas Heart Institute Journal

We sought to determine whether skeletal myoblasts, wild-type or engineered to express relaxin, might improve myocardial viability and performance in a rat model of chronic myocardial infarction. Our purpose was to investigate a potential new therapy for heart failure.

From October 2005 through September 2009, we surgically induced acute myocardial infarction in 80 male Wistar rats. Thirty days after surgery, the rats underwent reoperation for the retrograde coronary venous infusion of skeletal myoblasts, relaxin, or both. The animals were randomly assigned to 4 experimental groups: R1 (the control group, which underwent saline-solution infusion), R2 (systemic relaxin therapy), R3 (myoblast infusion), …

Micro-Ultrasonographic Imaging Of Atherosclerotic Progression And Correlation With Inflammatory Markers In Apolipoprotein-E Knockout Mice, Rong-Juan Li, Ya Yang, Yan-Hong Wang, Jin-Jie Xie, Li Song, Zheng Wang, Yao-Zhong Zhang, Yan-Wen Qin, Zhi-An Li, Xiao-Shan Zhang

The Texas Heart Institute Journal

We studied prospectively whether atherosclerotic progression in apolipoprotein-E knockout mice could be noninvasively and accurately measured by use of high-resolution ultrasonographic biomicroscopy. We examined the correlation between the ultrasonographic characterization of ascending aortic atherosclerotic plaque and plasma C-reactive protein, interleukin-1, and interleukin-6 levels in these mice.

In 4 age groups (8, 16, 24, and 32 wk) of 8 male knockout mice each (atherosclerotic groups) and age-matched male C57BL/6 mice (control groups), we used ultrasonographic biomicroscopy to measure maximal plaque thickness or intima-media thickness in the ascending aorta. We compared the findings with corresponding histologic measurements, and we measured plasma C-reactive …

Heterogeneity Of Left Ventricular Signal Characteristics In Response To Acute Vagal Stimulation During Ventricular Fibrillation In Dogs, Alireza Nazeri, Macarthur A Elayda, Lubomir Dragnev, Christopher M Frank, Jihong Qu, Valtino X Afonso, Abdi Rasekh, Mohammad Saeed, Jie Cheng, Mossaab Shuraih, Ali Massumi, Mehdi Razavi

The Texas Heart Institute Journal

Studies have shown that long-term vagal stimulation is protective against ventricular fibrillation; however, the effects of acute vagal stimulation during ventricular fibrillation in the normal heart have not been investigated. We examined the effects of acute vagal stimulation on ventricular fibrillation in a canine model. In 4 dogs, we induced 30-second periods of ventricular fibrillation by means of intraventricular pacing. During 2 of the 4 periods of fibrillation that we analyzed, vagal stimulation was delivered through electrodes in the caudal ends of the vagus nerves. Noncontact unipolar electrograms were recorded from 3 ventricular regions: the basal septum, apical septum, and …

Paclitaxel Induces Thrombomodulin Downregulation In Human Aortic Endothelial Cells, Huang-Joe Wang, Te-Ling Lu, Haimei Huang, Huey-Chun Huang

The Texas Heart Institute Journal

Patients with paclitaxel-eluting stents are at risk of developing stent thrombosis upon premature discontinuation of dual antiplatelet therapy. In this study, we set out to clarify whether paclitaxel can modulate thrombomodulin expression in human aortic endothelial cells. Human aortic endothelial cells were stimulated with paclitaxel. Methoxyphenyl tetrazolium inner salt cell viability assay, Western blot analysis, real-time polymerase chain reaction, and immunohistochemical assay were performed. In human aortic endothelial cells, paclitaxel (10(-5) to 10(-9) mol/L) treatment for 13 hours caused significant cytotoxicity at drug concentrations greater than 10(-7) mol/L. Paclitaxel (10(-5) to 10(-9) mol/L) treatment for 5 hours downregulated thrombomodulin expression …

Cardiac Dysfunction After Cancer Treatment, Michael S Ewer, Sandra M Swain, Daniela Cardinale, Anecita Fadol, Thomas M Suter

The Texas Heart Institute Journal

Onco-cardiology is an evolving discipline that requires the consideration of cardiotoxicity in preclinical, clinical,and therapeutic aspects of protocol development,treatment, and surveillance of patients who have undergone interventions using cardiotoxic agents. Only then can we foster new ways to maximize survival while keeping cardiac damage within acceptable limits. It is to this end that our working together has brought us to our present understanding. In the future, we may expect onco-cardiology to play an even greater role in the care of cancer patients.