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cardiac drugs

Renee Wei-Yan Chow, Paola Lamperti, Emily Steed, Francesco Boselli, Julien Vermot
During embryogenesis, cells undergo dynamic changes in cell behavior, and deciphering the cellular logic behind these changes is a fundamental goal in the field of developmental biology. The discovery and development of photoconvertible proteins have greatly aided our understanding of these dynamic changes by providing a method to optically highlight cells and tissues. However, while photoconversion, time-lapse microscopy, and subsequent image analysis have proven to be very successful in uncovering cellular dynamics in organs such as the brain or the eye, this approach is generally not used in the developing heart due to challenges posed by the rapid movement of the heart during the cardiac cycle...
February 20, 2018: Journal of Visualized Experiments: JoVE
Tianming Zhao, Jixiang Ni, Xuehua Hu, Yingnan Wang, Xinge Du
Thrombolysis and anticoagulation were the main treatment methods for acute pulmonary embolism. However, the use of thrombolysis drugs may lead to bleeding complications. We compared intermittent low-dose urokinase (UK) and alteplase (recombinant tissue plasminogen activator [rt-PA]) in normotensive patients with intermediate-high-risk pulmonary embolism. The UK group was treated with intravenous UK 10 000 U/kg once a day for 7 days. The rt-PA group was given alteplase 50 mg by intravenous injection within 2 hours of admission...
January 1, 2018: Clinical and Applied Thrombosis/hemostasis
Israel Ugalde, Ibrar Anjum, Saberio Lo Presti, Alfonso Tolentino
Acute coronary syndrome usually presents with retrosternal chest pain, nausea, vomiting, sweating, and jaw and arm pain. Some patients only present with neck, epigastric, or ear discomfort. A 47-year-old male with a history of hypertension and coronary artery disease presented to the emergency department complaining of bilateral otalgia. He never felt chest pain, jaw pain, nausea, diaphoresis, or shortness of breath. He had a history of 2 acute coronary events and had a stress test 2 months prior to admission, which was unremarkable...
January 2018: Journal of Investigative Medicine High Impact Case Reports
Karl Waked, Marc Schepens
During open thoracoabdominal aortic aneurysm repair (OTAAAR), there is an inevitable organ ischemic period that occurs when the abdominal arteries are being reattached to the aortic graft. Despite various protective techniques, the incidence of renal and visceral complications remains substantial. This state-of-the-art review gives an overview of the current and most evidence-based organ protection methods during OTAAAR, based on the most recent publications and personal experience. An electronic search was performed in four medical databases, using the following MeSH terms: thoracoabdominal aneurysm, TAAAR, visceral protection, renal protection, kidney, perfusion, and intestines...
2018: Journal of Visualized Surgery
Hairong Fu, Xiaoshan Li, Jiahua Tan
The main method for the treatment of acute myocardial infarction (AMI) is percutaneous coronary intervention; however percutaneous coronary intervention will induce ischemia/reperfusion (IR) injury, resulting in the loss of cardiac function and cardiomyocyte death. An effective drug to target this condition is necessary. N-isopropylacrylamide and methacrylic acid were used to synthesize drug delivery nanoparticles (NP) containing the natural compound visnagin for IR injury treatment. It was demonstrated that NP containing fluorescein isothiocyanate localized to the site of myocardial IR, and that NP-visnagin treatment induced cardioprotection, reducing the size of the MI and ameliorating cardiac dysfunction through the induction of autophagy and the inhibition of apoptosis...
April 2018: Oncology Letters
Paola Spitalieri, Rosa V Talarico, Silvia Caioli, Michela Murdocca, Annalucia Serafino, Marco Girasole, Simone Dinarelli, Giovanni Longo, Sabina Pucci, Annalisa Botta, Giuseppe Novelli, Cristina Zona, Ruggiero Mango, Federica Sangiuolo
Myotonic Dystrophy type 1 (DM1) is a multisystemic disease, autosomal dominant, caused by a CTG repeat expansion in DMPK gene. We assessed the appropriateness of patient-specific induced pluripotent stem cell-derived cardiomyocytes (CMs) as a model to recapitulate some aspects of the pathogenetic mechanism involving cardiac manifestations in DM1 patients. Once obtained in vitro, CMs have been characterized for their morphology and their functionality. CMs DM1 show intranuclear foci and transcript markers abnormally spliced respect to WT ones, as well as several irregularities in nuclear morphology, probably caused by an unbalanced lamin A/C ratio...
March 15, 2018: Journal of Molecular and Cellular Cardiology
Roberta Gualdani, Maria Maddalena Cavalluzzi, Francesco Tadini-Buoninsegni, Marino Convertino, Philippe Gailly, Anna Stary-Weinzinger, Giovanni Lentini
BACKGROUND/AIMS: Lubeluzole is a benzothiazole derivative that has shown neuroprotective properties in preclinical models of ischemic stroke. However, clinical research on lubeluzole is now at a standstill, since lubeluzole seems to be associated with the acquired long QT syndrome and ventricular arrhythmias. Since the cardiac cellular effects of lubeluzole have not been described thus far, an explanation for the lubeluzole-induced QT interval prolongation is lacking. METHODS: We tested the affinity of lubeluzole, its enantiomer, and the racemate for hERG channel using the patch-clamp technique...
March 10, 2018: Cellular Physiology and Biochemistry
Janusz Bednarski, Paweł Balsam, Agata Tymińska, Krzysztof Ozierański, Katarzyna Żukowska, Martyna Zaleska, Katarzyna Szepietowska, Kacper Maciejewski, Michał Peller, Anna Praska-Oginska, Inna Zaboyska, Grzegorz Opolski
INTRODUCTION Atrial fibrillation (AF) is the most common cardiac arrhythmia with a significant risk of morbidity and mortality. Non-vitamin K antagonists (NOAC) are the first line drugs in stroke prevention in AF patients. The oral anticoagulation therapy (OAC) therapy may differ between medical centres. OBJECTIVES The study aimed to compare the clinical characteristic of AF patients treated with OAC between district and academic hospitals. PATIENTS AND METHODS This analysis consisted of 3528 patients from the multicentre, retrospective CRAFT study (NCT02987062): 2666 patients from academic hospital (Group A) and 862 patients from district hospital (Group B)...
March 17, 2018: Polish Archives of Internal Medicine
Gian Paolo Fadini, Mayur Sarangdhar, Angelo Avogaro
INTRODUCTION: In the SAVOR-TIMI trial, the risk of heart failure (HF) was increased by 27% in T2D patients randomized to the dipeptidyl peptidase-4 inhibitor (DPP4i) saxagliptin. Other studies have provided inconsistent results regarding this association. Herein, we performed a pharmacovigilance analysis of the rate of HF associated with DPP4is, focusing on stimulated reporting and moderation by drug-drug interactions. METHODS: We mined the FDA adverse event (AE) reporting system (FAERS) from 2004q1 to 2017q3, including a total of 9906,642 AE reports...
March 16, 2018: Diabetes Therapy: Research, Treatment and Education of Diabetes and related Disorders
Hisao Otsuki, Junichi Yamaguchi, Kazuho Kamishima, Hiroyuki Arashi, Nobuhisa Hagiwara
Previous reports have focused on cardiovascular and bleeding events in patients with atrial fibrillation (AF) undergoing percutaneous coronary intervention (PCI). However, antithrombotic treatment strategies and clinical outcomes after second-generation drug-eluting stents (DES) implantation in AF patients remain to be determined. We enrolled 244 consecutive AF patients treated with second-generation DES. The study population was derived from multi-center AF registry (including 8 centers in Japan) from 2010 to 2012...
March 16, 2018: Heart and Vessels
Ilaria Depetris, Donatella Marino, Alessandro Bonzano, Celeste Cagnazzo, Roberto Filippi, Massimo Aglietta, Francesco Leone
Fluoropyrimidines (5-fluorouracil and capecitabine) are antimetabolite drugs, widely used for the treatment of a variety of cancers, both in adjuvant and in metastatic setting. Although the most common toxicities of these drugs have been extensively studied, robust data and comprehensive characterization still lack concerning fluoropyrimidine-induced cardiotoxicity (FIC), an infrequent but potentially life-threatening toxicity. This review summarizes the current state of knowledge of FIC with special regard to proposed pathogenetic models (coronary vasospasm, endothelium and cardiomyocytes damage, toxic metabolites, dihydropyrimidine dehydrogenase deficiency); risk and predictive factors; efficacy and usefulness in detection of laboratory markers, electrocardiographic changes and cardiac imaging; and specific treatment, including a novel agent, uridine triacetate...
April 2018: Critical Reviews in Oncology/hematology
Barbara Wiśniowska, Sebastian Polak
The current study is an example of drug-disease interaction modeling where a drug induces a condition which can affect the pharmacodynamics of other concomitantly taken drugs. The electrophysiological effects of hypokaliemia and heart rate changes induced by the antiasthmatic drugs were simulated with the use of the cardiac safety simulator. Biophysically detailed model of the human cardiac physiology-ten Tusscher ventricular cardiomyocyte cell model-was employed to generate pseudo-ECG signals and QTc intervals for 44 patients from four clinical studies...
March 15, 2018: Journal of Pharmacokinetics and Pharmacodynamics
Meng-Lin Liu, Meng-Long Wang, Jing-Jun Lv, Jie Wei, Jun Wan
Adriamycin (ADR) is a chemotherapeutic drug used to treat tumors in a clinical setting. However, its use is limited by a side effect of cardiotoxicity. Glibenclamide (Gli), an inhibitor of mitochondrial ATP-dependent potassium (K-ATP) channels, blocks the cardioprotective effects of mitochondrial K-ATP channel openers and induces apoptosis in rodent pancreatic islet β-cell lines. However, little is known about the role of Gli in ADR-induced cardiotoxicity. The present study was designed to investigate the impact of Gli on ADR-induced cardiotoxicity in rats...
April 2018: Experimental and Therapeutic Medicine
Adetola Ladejobi, Deepak K Pasupula, Shubash Adhikari, Awais Javed, Asad F Durrani, Shantanu Patil, Dingxin Qin, Shahzad Ahmad, Muhammad Bilal Munir, Shasank Rijal, Max Wayne, Evan Adelstein, Sandeep Jain, Samir Saba
BACKGROUND: Current guidelines recommend implantable cardioverter-defibrillator (ICD) therapy in survivors of sudden cardiac arrest (SCA), except in those with completely reversible causes. We sought to examine the impact of ICD therapy on mortality in survivors of SCA associated with reversible causes. METHODS AND RESULTS: We evaluated the records of 1433 patients managed at our institution between 2000 and 2012 who were discharged alive after SCA. A reversible and correctable cause was identified in 792 (55%) patients...
March 2018: Circulation. Arrhythmia and Electrophysiology
Matthew V Helliwell, Yihong Zhang, Aziza El Harchi, Chunyun Du, Jules C Hancox, Christopher E Dempsey
Cardiac potassium channels encoded by human Ether-à-go-go Related Gene (hERG) are major targets for structurally diverse drugs associated with acquired long QT syndrome. This study characterized hERG channel inhibition by a minimally structured high affinity hERG inhibitor, Cavalli-2, composed of three phenyl groups linked by polymethylene spacers around a central amino group, chosen to probe the spatial arrangement of side chain groups in the high-affinity drug binding site of the hERG pore. hERG current (IhERG ) recorded at physiological temperature from HEK 293 cells was inhibited with an IC50 of 35...
March 15, 2018: Journal of Biological Chemistry
Swetha Sangomla, Mohd Aslam Saifi, Amit Khurana, Chandraiah Godugu
Doxorubicin (DOX) is one of the most commonly used anticancer drugs but its use has been limited due to constraints of cardiotoxic side effects. The precise mechanism underlying cardiotoxicity is not yet fully understood but oxidative stress has been found to be a primary mechanism behind this. In addition, DOX induced cardiotoxicity also shows involvement of proinflammatory cytokines such as IL-6 and TNF-α. Since oxidative stress plays major role in DOX induced cardiotoxicity, different antioxidants have been tried to prevent cardiotoxicity of DOX...
May 2018: Journal of Trace Elements in Medicine and Biology
Ahmad Ali Amirghofran, Jamshid Badr, Mansour Jannati
BACKGROUND: Tetralogy of Fallot (TOF) is one of the congenital cardiac abnormality which occurs during embryonic time. Although surgical correction, especially early operation, is the best way to treat patients, still contributing factors in morbidity and mortality is controversial. The objective of this study is to investigate potential factors which might be correlated with post-operative outcomes of TOF. METHODS: In this retrospective study, 349 monitored patients with TOF correction were selected...
March 15, 2018: BMC Surgery
Paolo Calabrò, Felice Gragnano, Marco di Maio, Giuseppe Patti, Emilia Antonucci, Plinio Cirillo, Paolo Gresele, Gualtiero Palareti, Vittorio Pengo, Pasquale Pignatelli, Mauro Pennacchi, Antonino Granatelli, Stefano De Servi, Leonardo De Luca, Rossella Marcucci
The epidemiology and management of patients with acute coronary syndromes (ACSs) have evolved. We aimed to describe recent demographics and therapeutic changes in the Italian ACS population. We analyzed data from 2 multicenter consecutive Italian registries (the EYESHOT [EmploYEd antithrombotic therapies in patients with acute coronary Syndromes HOspitalised in iTalian cardiac care units] and START-ANTIPLATELET registries) enrolling patients with ACS between December 2013 and June 2016. An overall population of 3756 patients with ACS was enrolled: 2585 in the EYESHOT and 1171 in the START-ANTIPLATELET...
January 1, 2018: Angiology
Plansky Hoang, Jason Wang, Bruce R Conklin, Kevin E Healy, Zhen Ma
The creation of human induced pluripotent stem cells (hiPSCs) has provided an unprecedented opportunity to study tissue morphogenesis and organ development through 'organogenesis-in-a-dish'. Current approaches to cardiac organoid engineering rely on either direct cardiac differentiation from embryoid bodies (EBs) or generation of aligned cardiac tissues from predifferentiated cardiomyocytes from monolayer hiPSCs. To experimentally model early cardiac organogenesis in vitro, our protocol combines biomaterials-based cell patterning with stem cell organoid engineering...
April 2018: Nature Protocols
Nikunjkumar Patel, Oliver Hatley, Alexander Berg, Klaus Romero, Barbara Wisniowska, Debra Hanna, David Hermann, Sebastian Polak
Drug-induced cardiac arrhythmia, especially occurrence of torsade de pointes (TdP), has been a leading cause of attrition and post-approval re-labeling and withdrawal of many drugs. TdP is a multifactorial event, reflecting more than just drug-induced cardiac ion channel inhibition and QT interval prolongation. This presents a translational gap in extrapolating pre-clinical and clinical cardiac safety assessment to estimate TdP risk reliably, especially when the drug of interest is used in combination with other QT-prolonging drugs for treatment of diseases such as tuberculosis...
March 14, 2018: AAPS Journal
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