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Cardiovascular Toxicology

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https://www.readbyqxmd.com/read/29139031/in-vivo-analysis-of-the-anti-atrial-fibrillatory-proarrhythmic-and-cardiodepressive-profiles-of-dronedarone-as-a-guide-for-safety-pharmacological-evaluation-of-antiarrhythmic-drugs
#1
Yoshiyuki Motokawa, Yuji Nakamura, Mihoko Hagiwara-Nagasawa, Ai Goto, Koki Chiba, Nur Jaharat Lubna, Hiroko Izumi-Nakaseko, Kentaro Ando, Atsuhiko T Naito, Hiroshi Yamazaki, Atsushi Sugiyama
Anti-atrial fibrillatory, proarrhythmic and cardiodepressive profiles of dronedarone were analyzed using the halothane-anesthetized beagle dogs (n = 4) to create a standard protocol for clarifying both efficacy and adverse effects of anti-atrial fibrillatory drugs. Intravenous administration of dronedarone hydrochloride in doses of 0.3 and 3 mg/kg over 30 s attained the peak plasma concentrations of 61 and 1248 ng/mL, respectively, reflecting sub- to supra-therapeutic ones. The low dose decreased the left ventricular contraction and mean blood pressure, which were enhanced at the high dose...
November 14, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29134326/inhibition-of-the-voltage-dependent-k-current-by-the-tricyclic-antidepressant-desipramine-in-rabbit-coronary-arterial-smooth-muscle-cells
#2
Sung Eun Shin, Hongliang Li, Jin Ryeol An, Mi Seon Seo, Sung Hun Na, Won-Kyo Jung, Amy L Firth, Kwon-Soo Ha, Eun-Taek Han, Seok-Ho Hong, Il-Whan Choi, Won Sun Park
We describe the effect of a tricyclic antidepressant drug desipramine on voltage-dependent K(+) (Kv) currents in freshly isolated rabbit coronary arterial smooth muscle cells using a conventional whole-cell patch clamp technique. Application of desipramine rapidly decreased the Kv current amplitude in a concentration-dependent manner, with an IC50 value of 5.91 ± 0.18 μM and a Hill coefficient of 0.61 ± 0.09. The steady-state inactivation curves of the Kv channels were not affected by desipramine. However, desipramine shifted the steady-state inactivation curves toward a more negative potential...
November 13, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29110132/novel-mesenchymal-stem-cell-strategy-in-alleviating-toll-like-receptor-4-p53-and-nrf2-signaling-in-isoproterenol-induced-myocardial-infarction-in-rat-model
#3
Mai O Kadry, Rehab M Abdel-Megeed
Mesenchymal stem cells (MSCs) are multipotent stromal cells that merit the differentiation into various cell types. The present study was designed to test the hypothesis that the cardioprotective effect of MSCs transplantation and digoxin treatment is mediated via the regulation of messenger RNA gene expression of pro-inflammatory cytokines and apoptotic markers. Myocardial infarction was induced in Wistar rats via isoproterenol injection in a dose of (85 mg/kg, subcutaneously, twice at an interval of 24 h)...
November 6, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29094243/alleviation-of-cardiac-damage-by-dietary-fenugreek-trigonella-foenum-graecum-seeds-is-potentiated-by-onion-allium-cepa-in-experimental-diabetic-rats-via-blocking-renin-angiotensin-system
#4
Seetur R Pradeep, Krishnapura Srinivasan
Hyperglycemia is one of the metabolic and homeostatic abnormalities that increase the cardiovascular mortality in diabetic patients by increased oxidative stress. We have recently reported amelioration of oxidative stress in cardiac tissue by dietary fenugreek (Trigonella foenum-graecum) seeds and onion (Allium cepa) in streptozotocin-induced diabetic rats. The mechanistic aspects of the cardio-protective influence of dietary fenugreek seeds (10%) and onion (3% powder) both individually and in combination on hyperglycemia-mediated cardiac damage was further investigated in this study on streptozotocin-induced diabetic rats...
November 1, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29080123/beneficial-role-of-some-natural-products-to-attenuate-the-diabetic-cardiomyopathy-through-nrf2-pathway-in-cell-culture-and-animal-models
#5
REVIEW
V V Sathibabu Uddandrao, Parim Brahmanaidu, P R Nivedha, S Vadivukkarasi, Ganapathy Saravanan
Diabetic cardiomyopathy, as one of the main cardiac complications in diabetic patients, is identified to connect with oxidative stress that is due to interruption in balance between reactive oxygen species or/and reactive nitrogen species generation and their clearance by antioxidant protection systems. Transcription factor the nuclear factor erythroid 2-related factor 2 (Nrf2) plays a significant role in maintaining the oxidative homeostasis by regulating multiple downstream antioxidants. The Nrf2 plays a significant role in ARE-mediated basal and inducible expression of more than 200 genes that can be grouped into numerous categories as well as antioxidant genes and phase II detoxifying enzymes...
October 27, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/29022233/unanticipated-cardiotoxicity-associated-with-targeted-anticancer-therapy-in-patients-with-hematologic-malignancies-patients-natural-history-and-risk-factors
#6
Chintan Shah, Yan Gong, Anita Szady, Qian Sun, Carl J Pepine, Taimour Langaee, Alexandra R Lucas, Jan S Moreb
Our aim is to study unanticipated cardiotoxicity associated with the use of anticancer targeted agents, a problem that remains poorly understood. Using diagnosis codes, we retrospectively identified patients with both hematologic malignancies (HM) and cardiovascular diseases (n = 820 patients). Cardiotoxicity was defined per published criteria. The targeted agents of interest included tyrosine kinase inhibitors, proteasome inhibitors, monoclonal antibodies, and immunomodulatory agents. Patients found with cardiotoxicity (n = 29) were compared with 70 case-matched reference subjects...
October 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28986777/predicting-cardiotoxic-effects-of-carbon-monoxide-poisoning-using-speckle-tracking-echocardiography
#7
Erhan Saraçoğlu, Ertan Vuruşkan, Salih Kılıç, Yusuf Çekici, Bahaeddin Onur, Yavuz Arslan, Ertuğrul Kılıç, Ömer Aykut
Carbon monoxide (CO) poisoning could cause significant cardiac injury. This study aimed to evaluate patients with CO poisoning by using speckle tracking echocardiography (STE), a potentially more sensitive technique, to identify left systolic ventricular dysfunction for the first time in the literature. Seventy-two patients who were exposed to CO poisoning were studied. Blood collection and echocardiography were performed at admission and after patients' discharge on days 10-15 (mean 12 days). Global longitudinal strain (GLS) and global circumferential strain (GCS) were calculated using STE...
October 6, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28980197/xanthine-oxidase-activation-modulates-the-endothelial-vascular-dysfunction-related-to-hgcl2-exposure-plus-myocardial-infarction-in-rats
#8
Thaís de O Faria, Maylla Ronacher Simões, Dalton Valentim Vassallo, Ludimila Forechi, Camila Cruz Pereira Almenara, Bruna Antoniassi Marchezini, Ivanita Stefanon, Paula Frizera Vassallo
Heavy metal exposure is associated with cardiovascular diseases such as myocardial infarction (MI). Vascular dysfunction is related to both the causes and the consequences of MI. We investigated whether chronic exposure to low doses of mercury chloride (HgCl2) worsens MI-induced endothelial dysfunction 7 days after MI. Male Wistar rats were divided into four groups: Control (vehicle), HgCl2 (4 weeks of exposure), surgically induced MI and combined HgCl2-MI. Morphological and hemodynamic measurements were used to characterize the MI model 7 days after the insult...
October 4, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28895052/the-effects-of-periostin-in-a-rat-model-of-isoproterenol-mediated-cardiotoxicity
#9
Mahmut Sözmen, Alparslan K Devrim, Yonca B Kabak, Tuba Devrim, Mert Sudagidan
Periostin is an extracellular matrix protein from fasciclin family, and it plays an important role in the cell adhesion, migration, and growth of the organism. Periostin prevents apoptosis while stimulating cardiomyocytes. The present study was designed to investigate cardioprotective effects of the recombinant murine periostin peptide administration in a rat model of isoproterenol (ISO)-induced myocardial injury. The experiment was performed on 84 adult male Sprague Dawley rats in 4 groups (n = 21): control group (1), periostin-treated group (2), ISO-treated group (3), and ISO + periostin-treated group (4)...
September 11, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28856520/asiatic-acid-ameliorates-doxorubicin-induced-cardiac-and-hepato-renal-toxicities-with-nrf2-transcriptional-factor-activation-in-rats
#10
Sarika M Kamble, Chandragouda R Patil
Asiatic acid (AA), a pentacyclic triterpenoid, is a key phytoconstituent of Centella asiatica. AA is a patented as a cytotoxic substance, and it exerts cytotoxicity against Hep3B, Hela and MCF-7 cell lines. However, pentacyclic triterpenoids also modulate the expression and transcriptional activities of Nrf2 and exert cytoprotective effects. In this study, we investigated the effects of AA on the doxorubicin (DXR)-induced organ toxicities and expression of the Nrf2. DXR toxicity was induced by a single intravenous injection of 65...
August 30, 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28861837/cardiovascular-effects-of-the-mek-inhibitor-trametinib-a-case-report-literature-review-and-consideration-of-mechanism
#11
REVIEW
Mary Banks, Karen Crowell, Amber Proctor, Brian C Jensen
The MEK inhibitor trametinib was approved in 2013 for the treatment of unresectable or metastatic melanoma with a BRAF V600E mutation, the most common pathogenic mutation in melanoma. Trametinib blocks activation of ERK1/2, inhibiting cell proliferation in melanoma. ERK1/2 also protects against multiple types of cardiac insult in mouse models. Trametinib improves survival in melanoma patients, but evidence of unanticipated cardiotoxicity is emerging. Here we describe the case of a patient with metastatic melanoma who developed acute systolic heart failure after trametinib treatment and present the results of the literature review prompted by this case...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28853025/is-there-a-place-for-ozone-therapy-in-patients-with-heart-failure
#12
Bernardino Clavo, Khaled Eltobgy, Eduardo Caballero, Cipriano Abad, Francisco Rodríguez-Esparragón, Norberto Santana-Rodríguez
No abstract text is available yet for this article.
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28766181/treatment-of-amlodipine-intoxication-with-intravenous-lipid-emulsion-therapy-a-case-report-and-review-of-the-literature
#13
REVIEW
Funda Karbek Akarca, Ece Akceylan, Selahattin Kıyan
We report the case of a 25-year-old female presenting to the emergency department after committing suicide by ingesting 100 mg amlodipine. The patient was initially treated with intravenous fluids, calcium gluconate, catecholamines and glucagone without effect. The clinical condition of the patient improved quickly and dramatically on the 20th minute of intravenous lipid emulsion (ILE) therapy. Different treatment methods have been developed for calcium channel blocker intoxication over the last years. Among these, lipid emulsion therapy has risen over the last decade as a salvation in cases which do not respond to other treatments...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28534245/flecainide-induced-left-ventricular-dysfunction-fact-or-fiction
#14
Umair Khalid, Francia Rojas, Nasser Lakkis
No abstract text is available yet for this article.
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28283905/association-of-fasting-serum-bilirubin-levels-with-clinical-outcomes-after-percutaneous-coronary-intervention-a-prospective-study
#15
Ming-Ming Zhang, Ying Gao, Ying-Ying Zheng, You Chen, Fen Liu, Yi-Tong Ma, Xiang Xie
The aim is to investigate the association of fasting serum bilirubin (FSB) levels with the prognosis of coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI). A total of 450 hospitalized patients with CAD undergoing PCI were enrolled. The clinical data including FSB levels, basic biochemical indices, and traditional cardiovascular risk factors were recorded after admission, and all patients were followed up for 2.17 ± 0.67 years. The primary endpoint was the occurrence of major adverse cardiovascular events (MACE)...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28220374/lipopolysaccharide-activates-toll-like-receptor-4-and-prevents-cardiac-fibroblast-to-myofibroblast-differentiation
#16
Samir Bolívar, Roxana Santana, Pedro Ayala, Rodolfo Landaeta, Pía Boza, Claudio Humeres, Raúl Vivar, Claudia Muñoz, Viviana Pardo, Samuel Fernandez, Renatto Anfossi, Guillermo Diaz-Araya
Bacterial lipopolysaccharide (LPS) is a known ligand of Toll-like receptor 4 (TLR4) which is expressed in cardiac fibroblasts (CF). Differentiation of CF to cardiac myofibroblasts (CMF) is induced by transforming growth factor-β1 (TGF-β1), increasing alpha-smooth muscle actin (α-SMA) expression. In endothelial cells, an antagonist effect between LPS-induced signaling and canonical TGF-β1 signaling was described; however, it has not been studied whether in CF and CMF the expression of α-SMA induced by TGF-β1 is antagonized by LPS and the mechanism involved...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28213753/electrophysiologic-studies-on-the-risks-and-potential-mechanism-underlying-the-proarrhythmic-nature-of-azithromycin
#17
Mengdan Zhang, Ming Xie, Sha Li, Ying Gao, Shuyin Xue, Huili Huang, Kesu Chen, Fuming Liu, Long Chen
The mechanisms underlying arrhythmia induced by the clinical use of azithromycin are poorly understood. We aimed to investigate the proarrhythmic effects of azithromycin using electrocardiogram (ECG) and ion channel models. In vivo and in vitro guinea pig ECG and current and voltage clamp recordings were carried out. Azithromycin at 114.6 mg/kg (three times the clinically relevant dose) reduced heart rate (HR) and prolonged the PR, QRS and rate-corrected QT (QTc) intervals of guinea pig ECG in vivo. In vitro technique revealed that azithromycin at 207...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28194639/ultrafine-particulate-matter-increases-cardiac-ischemia-reperfusion-injury-via-mitochondrial-permeability-transition-pore
#18
Nathan A Holland, Chad R Fraiser, Ruben C Sloan, Robert B Devlin, David A Brown, Christopher J Wingard
Ultrafine particulate matter (UFP) has been associated with increased cardiovascular morbidity and mortality. However, the mechanisms that drive PM-associated cardiovascular disease and dysfunction remain unclear. We examined the impact of oropharyngeal aspiration of 100 μg UFP from the Chapel Hill, NC, air shed in Sprague-Dawley rats on cardiac function, arrhythmogenesis, and cardiac ischemia/reperfusion (I/R) injury using a Langendorff working heart model. We found that exposure to UFP was capable of significantly exacerbating cardiac I/R injury without changing overall cardiac function or major changes in arrhythmogenesis...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28185059/severe-proarrhythmic-potential-of-the-antiemetic-agents-ondansetron-and-domperidone
#19
Gerrit Frommeyer, Christina Fischer, Christian Ellermann, Philipp S Lange, Dirk G Dechering, Simon Kochhäuser, Michael Fehr, Lars Eckardt
The potential of ondansetron and domperidone, both clinically established antiemetic agents, to increase the QT-interval has been described in several case reports. Therefore, the aim of the present study was to investigate whether these drugs may provoke polymorphic ventricular tachycardia in a sensitive experimental model of drug-induced proarrhythmia. In 10 female rabbits, ondansetron (1, 5 and 10 µM, n = 10) or domperidone (0.5, 1 and 2 µM, n = 8) was infused after obtaining baseline data. Eight endo- and epicardial monophasic action potentials and a simultaneously recorded 12-lead ECG reproduced the clinically observed QT-prolongation (ondansetron: 1 µM:+17 ms, 5 µM:+41 ms, 10 µM:+78 ms, p < 0...
October 2017: Cardiovascular Toxicology
https://www.readbyqxmd.com/read/28097518/beneficial-effects-of-ozone-therapy-on-oxidative-stress-cardiac-functions-and-clinical-findings-in-patients-with-heart-failure-reduced-ejection-fraction
#20
Mutlu Buyuklu, Fatih Mehmet Kandemir, Turan Set, Eftal Murat Bakırcı, Husnu Degirmenci, Hikmet Hamur, Ergun Topal, Sefa Kucukler, Kultigin Turkmen
The aim of study was to determine the effects of ozone therapy on the oxidative stress, cardiac functions and clinical findings in patients with heart failure reduced ejection fraction (HFrEF). A total of 40 patients with New York Heart Association 2 and 3 HF with left ventricular ejection fraction (LVEF) <35%, and 40 subjects without HF as control group were included in the study. Patients with HFrEF were given additional ozone therapy of major and minor administrations along with conventional HF treatment for 5 weeks...
October 2017: Cardiovascular Toxicology
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