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Cardiovascular Toxicology

Hiroko Izumi-Nakaseko, Yuji Nakamura, Xin Cao, Takeshi Wada, Kentaro Ando, Atsushi Sugiyama
Since an antipsychotic drug haloperidol has been clinically reported to induce QT interval prolongation and torsade de pointes, in this study its risk stratification for the onset of torsade de pointes was performed by using the chronic atrioventricular block canine model with a Holter electrocardiogram. Haloperidol in a dose of 3 mg kg(-1) p.o. prolonged the QT interval, but it did not induce torsade de pointes during the observation period of 21 h (n = 4), indicating that the dose would be safe. Meanwhile, haloperidol in a dose of 30 mg kg(-1) p...
October 13, 2016: Cardiovascular Toxicology
Brian B Hasinoff, Daywin Patel, Xing Wu
Five clinically approved BCR-ABL1-targeted tyrosine kinase inhibitors (bosutinib, dasatinib, imatinib, nilotinib, and ponatinib) used for treating chronic myelogenous leukemia have been studied in a neonatal rat myocyte model for their relative ability to induce myocyte damage. This was done in order to determine if kinase inhibitor-induced myocyte damage was a consequence of inhibiting ABL1 (on-target effects), or due to a lack of kinase selectivity (off-target effects) since previous studies have come up with conflicting conclusions about whether imatinib-induced cardiotoxicity results directly from inhibition of ABL1...
September 30, 2016: Cardiovascular Toxicology
Mahsa Jafari Giv
With rapidly rising prevalence of exposure to Amphetamine Type Stimulants (ATS), novel insights into cardiotoxic effects of this substance are being presented in the literature and remarkably ATS Associated Cardiomyopathy (ATSAC) is emerging as a novel cardiovascular condition with its distinctive pathogenesis, risk factors, clinical features and prognosis. A comprehensive systematic review was performed to explore and analyze the current evidence on the association between ATS exposure and development of cardiomyopathy, biological mechanisms involved in pathogenesis of ATSAC, risk factors, clinical features and course of patients with ATSAC...
September 24, 2016: Cardiovascular Toxicology
Na-Na Ping, Yan-Ni Mi, Dong-Zheng Liu, Sai Zhang, Jing-Guo Chen, Yong-Xiao Cao
Cyclosporine A (CsA) induces hypertension after transplantation. Hydrogen sulfide (H2S) was found to have hypotensive/vasoprotective effects in the cardiovascular system. The present study aims to investigate the role of H2S on CsA-induced vascular function disorder in rats. Rats were subcutaneously injected with CsA 25 mg/kg for 21 days. Blood pressure was measured by the tail-cuff method. Vasomotion was determined using a sensitive myograph. Western blotting and immunohistochemistry were used to quantify the protein expression of endothelin type A (ETA) receptor and essential MAPK pathway molecules...
August 27, 2016: Cardiovascular Toxicology
M A Hieger, K F Maskell, M J Moss, S W Powell, K L Cumpston
Dofetilide is a class III antiarrhythmic used for treating atrial dysrhythmias. Though its adverse effects are well described in routine use, very little is known about dofetilide toxicity in overdose. This is a retrospective case series of consecutive patients reported to our poison center after dofetilide overdose. Twenty-seven cases were included. Seventeen patients were treated at a healthcare facility, and of these, eight were admitted. Twenty-one patients took one extra capsule, four took someone else's medication, one took three extra capsules, and one had a large intentional overdose...
August 26, 2016: Cardiovascular Toxicology
Hualin Yan, Yifei Li, Chuan Wang, Yi Zhang, Cong Liu, Kaiyu Zhou, Yimin Hua
microRNAs (miRNAs) belong to a class of non-coding RNAs that regulate post-transcriptional gene expression during development and disease. Growing evidence indicates abundant miRNA expression changes and their important role in cardiac hypertrophy and failure. However, the role of miRNAs in fetal cardiac remodeling is little known. Here, we investigated the altered expression of fifteen miRNAs in rat fetal cardiac remodeling compared with adult cardiac remodeling. Among fifteen tested miRNAs, eleven and five miRNAs (miR-199a-5p, miR-214-3p, miR-155-3p, miR-155-5p and miR-499-5p) are significantly differentially expressed in fetal and adult cardiac remodeling, respectively...
August 10, 2016: Cardiovascular Toxicology
Yingna Qiu, Ning Cong, Meng Liang, Yongqiang Wang, Jianshe Wang
In this paper, we investigated the multi-target effect of myricetin as a therapeutic for cardiovascular disease, using an acute ischemia/reperfusion-induced myocardial injury model to gain insight into its mechanism of action. The compound-target interaction profiles of myricetin were determined using a combination of text mining, chemometric and chemogenomic methods. The effect of myricetin on cardiac function was investigated by carrying out experiments in rats subjected to ischemia/reperfusion (I/R) using Langendorff retrograde perfusion technology...
August 2, 2016: Cardiovascular Toxicology
G S Ajithkumar, A Vinitha, S S Binil Raj, C C Kartha
Endocardial endothelial cells (EECs), when compared with endothelial cells of arteries and veins, possess higher resistance to apoptosis-inducing anticancer agents. The mechanism of this resistance property is unknown. We have investigated the molecular mechanism, which contributes to increased cell survival capacity in EECs. We explored whether the resistance to apoptosis is associated with the cellular expression of ATP-binding cassette transporters such as P-glycoprotein, MRP-1, and ABCG2. We used primary and immortalized porcine endocardial endothelial cells (PEECs and hTERT PEECs) and compared the results with that in porcine aortic endothelial cells (PAECs), left atrioventricular valve endothelial cells (PVECs), and human umbilical vein endothelial cell line (EA...
October 2016: Cardiovascular Toxicology
Sean Sliman, Jill Waalen, David Shaw
The purpose of this study was to determine the prevalence of methamphetamine-associated congestive heart failure (MAC) and to evaluate the relationship between methamphetamine abuse and EF and functional status over time. A retrospective review of records from 2009 to 2014 was carried out. Prevalence of methamphetamine abuse among all patients admitted with CHF was calculated for each of the 6 years of the study (n = 141) and was compared with prevalence of cocaine abuse and alcohol abuse. For patients with two or more admissions during the entire time period, the trajectories of NYHA functional class and EF over time were determined (n = 58)...
October 2016: Cardiovascular Toxicology
Burc Aydin, Nil Hocaoglu, Serap Cilaker Micili, Bekir Ugur Ergur, Sule Kalkan
The aim of this study was to investigate the efficacy of 2-hydroxypropyl-beta-cyclodextrin (HPBCD) as an antidotal treatment for the in vivo cardiovascular effects of amitriptyline poisoning. Experiments were carried out on 33 Wistar rats. To evaluate cardiovascular effects of HPBCD, rats were infused with dextrose or HPBCD. In the poisoning model, amitriptyline (0.94 mg/kg/min) was infused until the mean arterial blood pressure (MAP) dropped to 50 % of the baseline. Following amitriptyline infusion, dextrose, low-dose HPBCD (4...
October 2016: Cardiovascular Toxicology
Suwen Kumar, Tejaswini Joginpally, David Kim, Mrinal Yadava, Konchok Norgais, Heather S Laird-Fick
Consumer aerosol products can be inhaled for their psychoactive effects, but with attendant adverse health effects including "sudden sniffing death." Cardiomyopathy has rarely been described in association with 1,1-difluoroethane (DFE), a common aerosol propellant. We report a 33-year-old male who developed acute myocardial injury and global hypokinesis along with rhabdomyolysis, acute kidney injury, and fulminant hepatitis after 2 days' nearly continuous huffing. Workup for other causes, including underlying coronary artery disease, was negative...
October 2016: Cardiovascular Toxicology
Alex F Manini, Barry Stimmel, Robert S Hoffman, David Vlahov
Drug overdose is now the leading cause of injury-related mortality in the USA, but the prognostic utility of cardiac biomarkers is unknown. We investigated whether serum cardiac troponin I (cTnI) was associated with overdose mortality. This prospective observational cohort studied adults with suspected acute drug overdose at two university hospital emergency departments (ED) over 3 years. The endpoint was in-hospital mortality, which was used to determine test characteristics of initial/peak cTnI. There were 437 overdoses analyzed, of whom there were 20 (4...
October 2016: Cardiovascular Toxicology
Jin-Sun Park, Kyoung-Woo Seo, Byoung-Joo Choi, So-Yeon Choi, Myeong-Ho Yoon, Gyo-Seung Hwang, Seung-Jea Tahk, Sang-Cheon Choi, Young-Gi Min, Joon-Han Shin
Carbon monoxide (CO) intoxication could cause significant cardiac injury. Although cardiac dysfunction after CO intoxication can be presented, the echocardiographic findings after CO intoxication are poorly defined. The purpose of this study was to evaluate the clinical patterns of left ventricular (LV) systolic dysfunction using echocardiography. A total of 132 CO-intoxicated patients were enrolled. Clinical, demographic and laboratory data and echocardiographic findings were analyzed. The LV dysfunction group (29 patients) showed higher lactate level (5...
October 2016: Cardiovascular Toxicology
Mingming Zhang, Xietian Pan, Qian Zou, Yuesheng Xia, Jiangwei Chen, Qimeng Hao, Haichang Wang, Dongdong Sun
Notch3 and TGF-β1 signaling play a key role in the pathogenesis and progression of chronic cardiovascular disease. However, whether Notch3 protects against myocardial infarction (MI) and the underlying mechanisms remains unknown. C57BL/6 mice were randomized to be treated with Notch3 siRNA (siNotch3) or lentivirus carrying Notch3 cDNA (Notch3) before coronary artery ligation. Four weeks after constructing MI model, cardiac function and fibrosis were compared between groups. The cardiac fibroblast cells (CFs) were isolated from newborn C57BL/6 mice (1-3 days old) and transfected with lentivirus carrying Notch3 cDNA...
October 2016: Cardiovascular Toxicology
Mehmet Eyuboglu
Ventricular tachycardia (VT) is life-threatening subgroup of wide QRS complex tachycardia (WCT). VT is usually associated with structural heart diseases, but it can occur in the absence of any cardiovascular diseases. Adverse cardiac effect of sodium bicarbonate in healthy subjects is not well described. A 30-year-old healthy man with excessive intake of sodium bicarbonate-related VT is presented. He was using sodium bicarbonate during last 2 months to lose weight. He has no risk factors and any cardiovascular or systemic diseases...
October 2016: Cardiovascular Toxicology
Jie Qi, Xiao-Jing Yu, Xiao-Lian Shi, Hong-Li Gao, Qiu-Yue Yi, Hong Tan, Xiao-Yan Fan, Yan Zhang, Xin-Ai Song, Wei Cui, Jin-Jun Liu, Yu-Ming Kang
High-salt-induced inflammation and oxidative stress in the hypothalamic paraventricular nucleus (PVN) contribute to the pathogenesis of salt-sensitive hypertension. In this study, we hypothesized that chronic inhibition of nuclear factor-κB (NF-κB) activity in the PVN delays the progression of hypertension by upregulating anti-inflammatory cytokines, reducing NLRP3 (NOD-like receptor family pyrin domain containing 3) and IL-1β and attenuating p-IKKβ, NF-κB p65 activity and NAD(P)H oxidase in the PVN of salt-sensitive hypertensive rats...
October 2016: Cardiovascular Toxicology
Kais Mnafgui, Raouf Hajji, Fatma Derbali, Anis Gammoudi, Gaddour Khabbabi, Hedi Ellefi, Noureddine Allouche, Adel Kadri, Neji Gharsallah
This study aimed to evaluate the antithrombotic, anti-inflammatory and anti-cardiac remodeling properties of eugenol in isoproterenol-induced myocardial infarction in rats. Male Wistar rats were randomly divided into four groups, control, iso [100 mg/kg body weight was injected subcutaneously into rats at an interval of 24 h for 2 days (6th and 7th day) to induce MI] and pretreated animals with clopidogrel (0.2 mg/kg) and eugenol (50 mg/kg) orally for 7 days and intoxicated with isoproterenol (Iso + Clop) and (Iso + EG) groups...
October 2016: Cardiovascular Toxicology
Haijie Yu, Liye Shi, Shijie Zhao, Yujiao Sun, Yuan Gao, Yingxian Sun, Guoxian Qi
Triptolide is a bioactive component of Chinese herbal plant Tripterygium wilfordii Hook F that has recently been noted to attenuate hepatic and cerebral ischemia/reperfusion (I/R) injuries in rodents. To investigate whether triptolide could protect against myocardial I/R injuries, triptolide (25, 50 or 100 μg/kg) was administrated in Wistar rats that underwent left anterior descending coronary artery ligation in this study. Our data showed that triptolide pretreatment could attenuate myocardial infarction, increase the fractional shortening and left ventricular systolic pressure and decrease the left ventricular end-diastolic pressure in ischemic rats...
October 2016: Cardiovascular Toxicology
Asghar Rahmani, Koroush Soleimannejad, Mohammad Reza Hafezi Ahmadi, Khairollah Asadollahi, Zahra Khalighi
Previous studies have reported the harmful effects of exposure to phthalic acid (PA) on heart. No studies have reported the effects of prenatal PA exposure on the structure or function of heart. The current study aimed to investigate the effects of prenatal PA exposure on the markers of oxidative stress and cardiac structure in rats' offspring. Twenty-four pregnant rats were randomly categorized into three groups of control, exposed to 2.5 and 5 % PA. The morphometric properties of coronary arteries, markers of oxidative stress, and NOS activity were measured in offspring rats...
October 2016: Cardiovascular Toxicology
Michael A Valentino, Andrew Panakos, Loheetha Ragupathi, Janna Williams, Behzad B Pavri
In the setting of flecainide toxicity, supraventricular tachycardia can manifest as a bizarre right or left bundle branch block, sometimes with a northwest axis, and can easily be mistaken for ventricular tachycardia leading to inappropriate therapy. We conducted a comprehensive literature review for cases of flecainide toxicity. We found 21 articles of flecainide toxicity in adult patients in which 22 ECG tracings were published. In patients with flecainide toxicity and QRS duration ≤ 200 ms, the ECGs were more likely to show RBBB, visible P waves (p = 0...
July 19, 2016: Cardiovascular Toxicology
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