JournalTOCs

Cardiovascular Toxicology
Journal Prestige (SJR): 0.836

Citation Impact (citeScore): 2
Number of Followers: 8

Hybrid journal (It can contain Open Access articles)
ISSN (Print) 1559-0259 - ISSN (Online) 1530-7905
Published by Springer-Verlag

[2626 journals]

Interactive Effects of Omega-3 Polyunsaturated Fatty Acids and Secondhand
Smoke in Mice and Human Subjects
- Abstract: Abstract Active smoking and secondhand smoke (SHS) exposure increase the risk of cardiovascular morbidity and mortality. Active smoking is associated with reduced levels of omega-3 polyunsaturated fatty acids (n-3 PUFA) and studies show that n-3 PUFA supplementation can improve smoking-induced vascular dysfunction. However, the relationship between n-3 PUFA and SHS exposure has not been studied. Fat-1 transgenic mice, which convert n-6 to n-3 PUFA, were fed diets with n-3 PUFA or without (n-6 PUFA diet), exposed to air or SHS for 4 weeks, and vasoreactivity, antioxidant indices, and omega-3 index (percent eicosapentaenoic + docosahexaenoic acids in RBC) measured. Compared to air-exposed mice, SHS-enhanced aortic constriction in mice fed the n-6 PUFA diet (omega-3 index, 5.9 ± 0.2%; mean ± SE), but not in mice fed the n-3 PUFA diet (omega-3 index, 7.8 ± 0.6%). SHS also significantly induced mRNA expression of cytochrome P4501A1, NADPH:quinone oxidoreductase, heme oxygenase-1, and angiotensinogen in adipose tissue, and increased antioxidant capacity only in mice on the n-6 PUFA diet. Notably, SHS reduced the omega-3 index by 1.0 percentage point (p = 0.003), compared to air-exposed mice irrespective of diet. Additionally, we recruited human nonsmokers (NS) with and without SHS exposure (n = 40) 19–40 years old and measured the omega-3 index and antioxidant capacity. In human subjects SHS exposure was associated with a significantly lower omega-3 index (NS, 4.4 ± 1.1%; NS + SHS, 3.2 ± 1.0%; mean ± SD, p = 0.002) and higher antioxidant capacity (p < 0.001) than unexposed NS. Thus, SHS exposure is associated with lower levels of n-3 PUFA in mice and humans; however, an omega-3 index of ~ 8% in mice has vasoprotective and antioxidant properties.
  PubDate: 2021-02-01
Modulation of the Expression of Long Non-Coding RNAs H19, GAS5, and MIAT
by Endurance Exercise in the Hearts of Rats with Myocardial Infarction
- Abstract: Abstract Long non-coding RNAs (lncRNAs) have a critical role in the regulation of cardiovascular function. Dysregulation of lncRNAs is implicated in the progression of cardiovascular diseases including myocardial infarction (MI). Regarding the beneficial effects of exercise (Ex) on the improvement of MI, this study aimed to investigate the effects of post-MI Ex on the expression of MI-associated lncRNAs: H19, myocardial infarction association transcript (MIAT), and growth arrest specific 5 (GAS5). MI was induced by left anterior descending (LAD) coronary artery ligation in male Wistar rats. One week later, rats were exercised under a moderate-intensity protocol for 4 weeks. In the end, hemodynamic parameters and cardiac function indices were measured. Assessment of fibrotic areas and apoptosis was performed by Masson's trichrome staining and immunohistochemistry, respectively. Expression of genes was evaluated by real-time PCR. Ex significantly reduced the fibrotic areas (P < 0.05) and apoptosis and increased contractility indices (P < 0.01), and cardiac function (P < 0.05) in MI groups. The reduced expression of H19 (P < 0.01) in MI rats returned to normal levels by Ex. Ex significantly (P < 0.001) reduced the expression of MIAT and increased the expression of GAS5 (P < 0.01), which had changed in the hearts of rats with MI. The present study indicated the beneficial effect of Ex on the improvement of cardiac function and reduction of fibrosis in infarcted heart possibly through regulation of the expression of lncRNAs: H19, GAS5, and MIAT.
  PubDate: 2021-02-01
Bradykinin-Potentiating Activity of a Gamma-Irradiated Bioactive Fraction
Isolated from Scorpion ( Leiurus quinquestriatus ) Venom in Rats with
Doxorubicin-Induced Acute Cardiotoxicity: Favorable Modulation of
Oxidative Stress and Inflammatory, Fibrogenic and Apoptotic Pathways
- Abstract: Abstract Although doxorubicin (Dox) is a backbone of chemotherapy, the search for an effective and safe therapy to revoke Dox-induced acute cardiotoxicity remains a critical matter in cardiology and oncology. The current study was the first to explore the probable protective effects of native and gamma-irradiated fractions with bradykinin-potentiating activity (BPA) isolated from scorpion (Leiurus quinquestriatus) venom against Dox-induced acute cardiotoxicity in rats. Native or irradiated fractions (1 μg/g) were administered intraperitoneally (i.p.) twice per week for 3 weeks, and Dox (15 mg/kg, i.p.) was administered on day 21 at 1 h after the last native or irradiated fraction treatment. Electrocardiographic (ECG) aberrations were ameliorated in the Dox-treated rats pretreated with the native fraction, and the irradiated fraction provided greater amelioration of ECG changes than that of the native fraction. The group pretreated with native protein with BPA also exhibited significant improvements in the levels of oxidative stress-related, inflammatory, angiogenic, fibrogenic, and apoptotic markers compared with those of the Dox group. Notably, the irradiated fraction restored these biomarkers to their normal levels. Additionally, the irradiated fraction ameliorated Dox-induced histological changes and alleviated the severity of cardiac injury to a greater extent than that of the native fraction. In conclusion, the gamma-irradiated detoxified fraction of scorpion venom elicited a better cardioprotective effect than that of the native fraction against Dox-induced acute cardiotoxicity in rats.
  PubDate: 2021-02-01
Thioredoxin Decreases Anthracycline Cardiotoxicity, But Sensitizes Cancer
Cell Apoptosis
- Abstract: Abstract Cardiotoxicity is a major limitation for anthracycline chemotherapy although anthracyclines are potent antitumor agents. The precise mechanism underlying clinical heart failure due to anthracycline treatment is not fully understood, but is believed to be due, in part, to lipid peroxidation and the generation of free radicals by anthracycline-iron complexes. Thioredoxin (Trx) is a small redox-active antioxidant protein with potent disulfide reductase properties. Here, we present evidence that cancer cells overexpressing Trx undergo enhanced apoptosis in response to daunomycin. In contrast, cells overexpressing redox-inactive mutant Trx were not effectively killed. However, rat embryonic cardiomyocytes (H9c2 cells) overexpressing Trx were protected against daunomycin-mediated apoptosis, but H9c2 cells with decreased levels of active Trx showed enhanced apoptosis in response to daunomycin. We further demonstrate that increased level of Trx is specifically effective in anthracycline toxicity, but not with other topoisomerase II inhibitors such as etoposide. Collectively these data demonstrate that whereas high levels of Trx protect cardiomyocytes against anthracycline toxicity, it potentiates toxicity of anthracyclines in cancer cells.
  PubDate: 2021-02-01
Identification of Clinical and Laboratory Variables Associated with
Cardiotoxicity Events Due to Doxorubicin in Breast Cancer Patients: A
1-Year Follow-Up Study
- Abstract: Abstract Cardiovascular adverse events in patients with breast cancer undergoing chemotherapy (CT) are frequent due to the high cardiotoxic potential of treatments, especially doxorubicin (DOXO). This study aimed to evaluate the association of plasma levels of various biomarkers with cardiotoxicity in women with breast cancer on DOXO-based chemotherapy. In this single center prospective cohort, 80 breast cancer patients who used DOXO as a first-line treatment for cancer were evaluated. Patients were assessed at three time points: before CT (T0), 1 week after (T1) and 12 months after DOXO treatment (T2). The predominant histological classification was ductal carcinoma, n = 72 (90.0%); the most frequent molecular classification was Human epidermal growth factor receptor-type 2 positive (HER2+), n = 34 (43.0%). In patients submitted to complementary treatment with trastuzumab (n = 23), there was no association with cardio-specific biomarkers. Evaluating the clinical variables and the laboratory parameters in T1 and T2 in relation to T0, the reduction any time of N-terminal-pro hormone B-type natriuretic peptide (NT-proBNP), triglycerides and hematocrit levels showed an association with higher cardiotoxicity risk. In addition, increased levels of troponin I (cTnI) and glycated hemoglobin (HbA1c) showed an independent association with the occurrence of cardiotoxicity. These results suggest that the evaluation of these laboratory tests should be included routinely to identify breast cancer patients under DOXO treatment at cardiotoxicity risk.
  PubDate: 2021-02-01
Smoking Accelerates Atrioventricular Conduction in Humans Concordant with
Increased Dopamine Release
- Abstract: Abstract Smoking is associated with cardiac arrhythmia, stroke, heart failure, and sudden cardiac arrest, all of which may derive from increased sympathetic influence on cardiac conduction system and altered ventricular repolarization. However, knowledge of the effects of smoking on supraventricular conduction, and the role of the sympathetic nervous system in them, remains incomplete. Participants with intermediate-high cardiovascular disease risk were measured for urinary catecholamines and cotinine, and 12-lead electrocardiograms (ECGs) were measured for atrial and atrioventricular conduction times, including P duration, PR interval, and PR segment (lead II), which were analyzed for associations with cotinine by generalized linear models. Statistical mediation analyses were then used to test whether any significant associations between cotinine and atrioventricular conduction were mediated by catecholamines. ECG endpoints and urinary metabolites were included from a total of 136 participants in sinus rhythm. Atrial and atrioventricular conduction did not significantly differ between smokers (n = 53) and non-smokers (n = 83). Unadjusted and model-adjusted linear regressions revealed cotinine significantly and inversely associated with PR interval and PR segment, but not P duration. Dopamine, norepinephrine, and epinephrine all inversely associated with PR interval, whereas only dopamine was also inversely associated with PR segment (p < 0.05). Dopamine and norepinephrine (but not epinephrine) also associated positively with cotinine. Dopamine mediated the relationship between cotinine and PR interval, as well as the relationship between cotinine and PR segment. Smoking is associated with accelerated atrioventricular conduction and elevated urinary dopamine and norepinephrine. Smoking may accelerate atrioventricular nodal conduction via increased dopamine production.
  PubDate: 2021-02-01
Caspofungin Effects on Electrocardiogram of Mice: An Evaluation of Cardiac
Safety
- Abstract: Abstract Caspofungin is an echinocandin, exhibiting efficacy against most Candida species invasive infection. Its cardiotoxicity was reported in isolated rat heart and ventricular myocytes, but in vivo and clinical studies are insufficient. Our objective was to evaluate caspofungin in vivo cardiac effects using an efficacious dose against Candida albicans. Female Swiss mice were infected with C. albicans, and treated with caspofungin, 5 or 10 mg/kg, intraperitoneal along 5 days. Survival rate and colony-forming units (CFU) into vital organs were determined. For cardiac effects study, mice were treated with caspofungin 10 mg/kg, and electrocardiogram (ECG) signal was obtained on C. albicans-infected mice, single dose-treated, and uninfected mice treated along 5 days, both groups to measure ECG intervals. Besides, ECG was also obtained by telemetry on uninfected mice to evaluate heart rate variability (HRV) parameters. The MIC for caspofungin on the wild-type C. albicans SC5314 strain was 0.3 μg/ml, indicating the susceptible. Survival rate increased significantly in infected mice treated with caspofungin compared to mice treated with vehicle. None of the survived infected mice presented positive CFU after treatment with 10 mg/kg. C. albicans infection induced prolongation of QRS, QT, and QTc intervals; caspofungin did not alter this effect. Caspofungin induced increase of PR and an additional increase of QRS after 24 h of a single dose in infected mice. No significant alterations occurred in ECG intervals and HRV parameters of uninfected mice, after caspofungin treatment. Caspofungin showed in vivo cardiac relative safety maintaining its antifungal efficacy against C. albicans.
  PubDate: 2021-02-01
Doxorubicin Cytotoxicity in Differentiated H9c2 Cardiomyocytes: Evidence
for Acute Mitochondrial Superoxide Generation
- Abstract: Abstract Although a mitochondrial redox-cycling superoxide-generating mechanism for the cardiotoxicity of doxorubicin was suggested from experiments with isolated mitochondria, its occurrence and contribution to cytotoxicity in intact cardiomyocytes is not fully established. Therefore, we determined the immediate and delayed effects of doxorubicin on the generation of reactive oxygen species (ROS) and cytotoxicity in differentiated H9c2 cardiomyocytes. Although relatively short incubations (3 or 6 h) with 1 or 5 µM doxorubicin did not acutely decrease cell survival, exposure to 5 µM doxorubicin for 3 h was sufficient to cause a significant delayed decrease in cell survival after an additional 24 h without doxorubicin. Mitochondrial superoxide generation was observed to increase within 30 min of incubation with 5 µM doxorubicin. Increased intracellular ROS generation, decreased mitochondrial metabolic activity, and decreased mitochondrial membrane potential (MMP) were observed after more extended periods (6–12 h). Overall, these observations support that the toxicity of doxorubicin to differentiated cardiomyocytes involves acute mitochondrial superoxide generation with subsequent intracellular ROS generation, mitochondrial dysfunction, and cell death.
  PubDate: 2021-02-01
Recurrent Takotsubo Cardiomyopathy Associated with Opioid Withdrawal
During Buprenorphine Induction
- Abstract: Abstract This case report describes a 65-year-old female with iatrogenic opioid use disorder for chronic lower back pain, who developed Takotsubo cardiomyopathy on multiple occasions following buprenorphine induction. This patient had three opioid transfers to buprenorphine, over 4 years, two of which were complicated by Takotsubo cardiomyopathy. In the transfer where she did not develop Takotsubo cardiomyopathy, she was treated with high doses of the centrally acting agonist, clonidine (three times a day, total of 600 mcg/day), up to and including the day of her transfer. This case highlights the potential consequences of a precipitated withdrawal with buprenorphine in an opioid transfer and its possible prevention with clonidine. To our knowledge, this is the first description of the recurrent Takotsubo cardiomyopathy in an opioid transfer setting. Given that buprenorphine is a partial agonist, in the presence of a full opioid agonist, it can precipitate withdrawal within minutes to hours of its administration. Opioid withdrawal can result in a sympathetic overdrive. Although complications of opioid withdrawal are extensively documented, cardiotoxicity is uncommon. As the use of buprenorphine and its new injectable formulations rise, it is important for prescribers to be aware of this life threatening complication. The prophylactic administration of clonidine can be considered to reduce the risk of cardiotoxicity, as well as manage opioid withdrawal symptoms.
  PubDate: 2021-01-22
Acute Exposure of Atmospheric Ultrafine Particles Induced Inflammation
Response and Dysregulated TGFβ/Smads Signaling Pathway in ApoE −/−
Mice
- Abstract: Abstract Ultrafine particles (UFPs) referred to particular matters with aerosol diameter less than 100 nm. Because of the lightweight and small size, UFPs have become an occupational inhalation risk. The UFPs will be accumulated in the deep lung through inhalation, and then reach into all the organs via circulation system; some UFPs even stay in the brain. As previous study reported, UFPs exposure is usually associated with cardiovascular disease, such as atherosclerosis (AS). In our study, we tried to understand how acute UFP exposure caused the biological dysregulation in atherosclerosis. Acute exposure of UFPs were applied to mice for 6 consecutive days, mice were sacrificed after 3, 5, 7, and 10 days post-exposure. Aorta and serum were collected for histological and biomarkers analysis. Mice aortic adventitial fibroblasts (MAFs) were isolated from mice and used to further study to understand the mechanism of UFPs induced atherosclerosis. Compared to the untreated control, the inflammation responses and nitrate stress were observed after acute exposure of UFPs, with increased IL-6, MCP-1, p47phox, and 3-NT levels in the mice serum. Besides, upregulation of microRNAs: miR-301b-3p and Let-7c-1-3p, and their downstream target: Smad2, Smad3, and TGFβ1 were also observed in mouse aorta after acute exposure of UFPs. Similar results were identified in vitro as well. Acute exposure of UFPs induced the systematic nitrate stress and inflammation responses, along with the changes of vascular permeability. Dysregulated miRNAs and TGFβ/Smads signaling pathway indicated the higher risk of atherosclerosis/vasculature remodeling when exposed to UFPs.
  PubDate: 2021-01-21
miR-362-3p Targets Orosomucoid 1 to Promote Cell Proliferation, Restrain
Cell Apoptosis and Thereby Mitigate Hypoxia/Reoxygenation-Induced
Cardiomyocytes Injury
- Abstract: Abstract This study aimed to investigate the mechanism of how miR-362-3p/orosomucoid 1 (ORM1) involved in hypoxia/reoxygenation (H/R)-induced cardiomyocytes injury. Based on data obtained from Gene Expression Omnibus (GEO) database, we revealed that ORM1 was highly expressed and positively correlated with the expression of inflammatory factors (MAPK1, MAPK3, IL1B and CASP9). miR-362-3p was identified as an upstream regulatory miRNA of ORM1 and negatively modulated the mRNA and protein expression levels of ORM1 in H/R-injured cardiomyocytes. Moreover, we found that miR-362-3p was downregulated in cardiomyocytes injured by H/R. The promoting influence of miR-362-3p mimic on the proliferation and the inhibitory effect of miR-362-3p mimic on the apoptosis of H/R-stimulated cardiomyocytes were eliminated by overexpression of ORM1. Furthermore, miR-362-3p affected the expression of MAPK1, MAPK3, IL1B and CASP9 in H/R-injured cardiomyocytes through targeting ORM1. Our outcomes illustrated that miR-362-3p exhibited a protective influence on H/R-induced cardiomyocytes through targeting ORM1.
  PubDate: 2021-01-18
Mitochondrial Sirtuins and Doxorubicin-induced Cardiotoxicity
- Abstract: Abstract Doxorubicin (DOX) is the most effective and extensively used treatment for many tumors. However, its clinical use is hampered by its cardiotoxicity. DOX-induced mitochondrial dysfunction, which causes reactive oxygen species (ROS) generation, cardiomyocyte death, bioenergetic failure, and decreased cardiac function, is a very important mechanism of cardiotoxicity. These cellular processes are all linked by mitochondrial sirtuins (SIRT3–SIRT4). Mitochondrial sirtuins preserve mitochondrial function by increasing mitochondrial metabolism, inhibiting ROS generation by activating the antioxidant enzyme manganese-dependent superoxide dismutase (MnSOD), decreasing apoptosis by activating the forkhead homeobox type O (FOXO) and P53 pathways, and increasing autophagy through AMP-activated protein kinase (AMPK)/mTOR signaling. Thus, sirtuins function at the control point of many mechanisms involved in DOX-induced cardiotoxicity. In this review, we focus on the role of mitochondrial sirtuins in mitochondrial biology and DOX-induced cardiotoxicity. A further aim is to highlight other mitochondrial processes, such as autophagy (mitophagy) and mitochondrial quality control (MQC), for which the effect of mitochondrial sirtuins on cardiotoxicity is unknown.
  PubDate: 2021-01-12
Potential Role of Serum S-100β Protein as a Predictor of Cardiotoxicity
and Clinical Poor Outcome in Acute Amphetamine Intoxication
- Abstract: Abstract Cardio- and neurotoxicity of amphetamines play an important role in worsening morbidity, making the initial evaluation of the patient’s status a potentially lifesaving action. The current study hypothesized that the S-100β serum level could predict the severity of acute amphetamine toxicity and the in-hospital outcome. The current study is a prospective cohort study conducted on 77 patients diagnosed with acute amphetamine exposure and referred to Aseer Poison Control Center, Saudi Arabia. The patients admitted to ICU showed significantly higher serum levels of S-100β in comparison to those not admitted (p < 0.05). Moreover, the S-100β level was significantly elevated among patients with prolonged QTc intervals. Receiver-operating characteristic curve of S-100β serum level as an in-hospital outcome predictor showed that at a cutoff value > 0.430 ug/L, the sensitivity of S-100β serum level as severity predictor was 100%, and the specificity was 74.1%. In conclusion, the current study revealed that the S-100β serum level could be used as an outcome predictor in hospital admission cases due to toxic amphetamine exposure and offers an idea about the cardiac and neuronal involvement. This can help select patients who will benefit most from ICU admission and early management and assess the severity of cases in settings where GC–MS is not available.
  PubDate: 2021-01-09
Validation of Corrected and Dispersed QT as Predictors of Adverse Outcomes
in Acute Cardiotoxicities
- Abstract: Abstract Acute cardiovascular poisoning is a major cause of adverse outcomes in poisoning emergencies. The prognostic validity of corrected QT (QTc) and dispersed QT (QTd) in these outcomes is still limited. The present study aimed to determine the risk factors of mortality, adverse cardiovascular events (ACVE), and intensive care unit (ICU) admission in patients with acute cardiovascular toxicities and assess the validity of QTc and QTd intervals in predicting these outcomes. This study was conducted on adult patients admitted to Tanta University Poison Control Center with a history of acute cardiotoxic drugs or toxins exposure. The demographic and toxicological data of patients were recorded. Clinical examination, routine laboratory investigations, ECG grading, and measurement of QTc and QTd were performed. The patients were grouped according to their adverse outcomes. Among the included patients, 51 (31.48%) patients died, 61 (37.65%) patients had ACVE, and 68 (41.98%) patients required ICU admission. The most common cause of poisoning is aluminum phosphide, followed by cholinesterase inhibitors. QTd and QTdc showed no significant difference among outcome groups. The best cut-off values of QTc to predict mortality, ACVE, and ICU admission were > 491.1 ms, > 497.9 ms, and ≥ 491.9 ms, respectively. The derived cut-off QTc values were independent predictors for all adverse outcomes after adjusting for poison type, serum HCO3, and pulse. The highest odds ratios for all adverse outcomes were observed in aluminum phosphide poisoning and low HCO3 < 18 mmol/L. Thus, serum HCO3 and QTc interval should be monitored for acute cardiotoxicities, especially in aluminum phosphide and cholinesterase inhibitors poisoning.
  PubDate: 2021-01-05
Effects of Melatonin and Adrenomedullin in Reducing the Cardiotoxic
Effects of Doxorubicin in Rats
- Abstract: Abstract The main disadvantage of doxorubicin (DOX) is that it has cardiotoxic side effects. Our aim is to evaluate the cardioprotective effects of adrenomedullin (ADM) and to compare these effects with melatonin (MEL), it’s cardioprotective effects are well known. Rats were divided into four groups: Control group (0.9% NaCl solution, intravenously), Doxorubicin group (45 mg/kg DOX, intravenously), Doxorubicin + Melatonin group (DOX + MEL, 10 mg/kg melatonin, intraperitoneally), Doxorubicin + Adrenomedullin group (DOX + ADM, 12 µg/kg adrenomedullin, intraperitoneally). A single dose of DOX was injected to the experimental groups on day 5, and a single dose of 0.9% NaCl solution was injected to the control group through the tail vein. The animals were anesthetized and ECG recordings were obtained on day 8. For the purpose of biochemical and histological analysis, cardiac tissue biopsy was obtained after ECG recordings. Compared to the control group, the DOX group had significantly increased duration of QRS complex, PR interval, QT interval and QTc interval. QRS complex, QT interval and QTc interval were prolonged with the administration of DOX and shortened with the administration of ADM. MEL weakened the toxic effects of DOX on the cardiac tissue and it is shown histologically. DOX increased interleukins (IL-1α, IL-6, IL-18), tumor necrosis factor-α (TNF-α), hypoxia-inducible factor 1-alpha (HIF-1α), malondialdehyde (MDA), nitric oxide (NO), creatine kinase myocardial band (CK-MB), and total oxidant status (TOS) levels in cardiac tissue, while reducing total antioxidant status (TAS), superoxide dismutase (SOD) and catalase (CAT) levels. MEL administration decreased the levels of CK-MB, MDA, IL-1α, IL-6, IL-18, NO, and TNF-α, whereas ADM only decreased IL-1α, IL-18, MDA and TNF-α levels. In summary, these results show that DOX has toxic effects on rat cardiac tissue which is documented histologically, electrocardiographically and biochemically. MEL alleviated histological damage and showed improvement on the several biochemical parameters of cardiac tissue. ADM brought several electrocardiographic and biochemical parameters closer to normal values.
  PubDate: 2021-01-03
Exposure to Intermittent Noise Exacerbates the Cardiovascular Response of
Wistar–Kyoto Rats to Ozone Inhalation and Arrhythmogenic Challenge
- Abstract: Abstract Noise has become a prevalent public health problem across the world. Although there is a significant amount of data demonstrating the harmful effects of noise on the body, very little is known about how it impacts subsequent responses to other environmental stressors like air pollution, which tend to colocalize in urban centers. Therefore, this study was conducted to determine the effect of intermittent noise on cardiovascular function and subsequent responses to ozone (O3). Male Wistar–Kyoto rats implanted with radiotelemeters to non-invasively measure heart rate (HR) and blood pressure (BP), and assess heart rate variability (HRV) and baroreflex sensitivity (BRS) were kept in the quiet or exposed to intermittent white noise (85–90 dB) for one week and then exposed to either O3 (0.8 ppm) or filtered air. Left ventricular function and arrhythmia sensitivity were measured 24 h after exposure. Intermittent noise caused an initial increase in HR and BP, which decreased significantly later in the regimen and coincided with an increase in HRV and BRS. Noise caused HR and BP to be significantly elevated early during O3 and lower at the end when compared to animals kept in the quiet while the increased HRV and BRS persisted during the 24 h after. Lastly, noise increased arrhythmogenesis and may predispose the heart to mechanical function changes after O3. This is the first study to demonstrate that intermittent noise worsens the cardiovascular response to inhaled O3. These effects may occur due to autonomic changes and dysregulation of homeostatic controls, which persist one day after exposure to noise. Hence, co-exposure to noise should be taken into account when assessing the health effects of urban air pollution.
  PubDate: 2021-01-03
Interrelated In Vitro Mechanisms of Sibutramine-Induced Cardiotoxicity
- Abstract: Abstract Consumption of illicit pharmaceutical products containing sibutramine has been reported to cause cardiovascular toxicity problems. This study aimed to demonstrate the toxicity profile of sibutramine, and thereby provide important implications for the development of more effective strategies in both clinical approaches and drug design studies. Action potentials (APs) were determined from freshly isolated ventricular cardiomyocytes with whole-cell configuration of current clamp as online. The maximum amplitude of APs (MAPs), the resting membrane potential (RMP), and AP duration from the repolarization phases were calculated from original records. The voltage-dependent K+-channel currents (IK) were recorded in the presence of external Cd2+ and both inward and outward parts of the current were calculated, while their expression levels were determined with qPCR. The levels of intracellular free Ca2+ and H+ (pHi) as well as reactive oxygen species (ROS) were measured using either a ratiometric micro-spectrofluorometer or confocal microscope. The mechanical activity of isolated hearts was observed with Langendorff-perfusion system. Acute sibutramine applications (10–8–10−5 M) induced significant alterations in both MAPs and RMP as well as the repolarization phases of APs and IK in a concentration-dependent manner. Sibutramine (10 μM) induced Ca2+-release from the sarcoplasmic reticulum under either electrical or caffeine stimulation, whereas it depressed left ventricular developed pressure with a marked decrease in the end-diastolic pressure. pHi inhibition by sibutramine supports the observed negative alterations in contractility. Changes in mRNA levels of different IK subunits are consistent with the acute inhibition of the repolarizing IK, affecting AP parameters, and provoke the cardiotoxicity.
  PubDate: 2021-01-03
Editorial: From the Editor-in-Chief
- PubDate: 2021-01-02
QTc Prolongation in COVID-19 Patients Using Chloroquine
- Abstract: Abstract Chloroquine is used in the treatment of patients with COVID-19 infection, although there is no substantial evidence for a beneficial effect. Chloroquine is known to prolong the QRS and QTc interval on the ECG. To assess the effect of chloroquine on QRS and QTc intervals in COVID-19 patients, we included all inpatients treated with chloroquine for COVID-19 in the Spaarne Gasthuis (Haarlem/Hoofddorp, the Netherlands) and had an ECG performed both in the 72 h before and during or at least 48 h after treatment. We analyzed the (change in) QRS and QTc interval using the one-sample t-test. Of the 106 patients treated with chloroquine, 70 met the inclusion criteria. The average change in QRS interval was 6.0 ms (95% CI 3.3–8.7) and the average change in QTc interval was 32.6 ms (95% CI 24.9–40.2) corrected with the Bazett’s formula and 38.1 ms (95% CI 30.4–45.9) corrected with the Fridericia’s formula. In 19 of the 70 patients (27%), the QTc interval was above 500 ms after start of chloroquine treatment or the change in QTc interval was more than 60 ms. A heart rate above 90 bpm, renal dysfunction, and a QTc interval below 450 ms were risk factors for QTc interval prolongation. Chloroquine prolongs the QTc interval in a substantial number of patients, potentially causing rhythm disturbances. Since there is no substantial evidence for a beneficial effect of chloroquine, these results discourage its use in COVID-19 patients.
  PubDate: 2021-01-02
Resistance training improves cardiac function and cardiovascular autonomic
control in doxorubicin-induced cardiotoxicity
- Abstract: Abstract Doxorubicin (DOX) is an anticancer chemotherapy drug that is widely used in clinical practice. It is well documented that DOX impairs baroreflex responsiveness and left ventricular function and enhances sympathetic activity, cardiac sympathetic afferent reflexes and oxidative stress, which contribute to hemodynamic deterioration. Because resistance training (RT)-induced cardioprotection has been observed in other animal models, the objective of this study was to assess the effects of RT during DOX treatment on hemodynamics, arterial baroreflex, cardiac autonomic tone, left ventricular function and oxidative stress in rats with DOX-induced cardiotoxicity. Male Wistar rats were submitted to a RT protocol (3 sets of 10 repetitions, 40% of one-repetition maximum (1RM) of intensity, 3 times per week, for 8 weeks). The rats were separated into 3 groups: sedentary control, DOX sedentary (2.5 mg/kg of DOX intraperitoneal injection, once a week, for 6 weeks) and DOX + RT. After training or time control, the animals were anesthetized and 2 catheters were implanted for hemodynamic, arterial baroreflex and cardiac autonomic tone. Another group of animals was used to evaluate left ventricular function. We found that RT in DOX-treated rats decreased diastolic arterial pressure, heart rate, sympathetic tone and oxidative stress. In addition, RT increased arterial baroreflex sensitivity, vagal tone and left ventricular developed pressure in rats with DOX-induced cardiotoxicity. In summary, RT is a useful non-pharmacological strategy to attenuate DOX-induced cardiotoxicity.
  PubDate: 2021-01-02