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Exposure to nanoparticles derived from diesel particulate filter equipped engine increases vulnerability to arrhythmia in rat hearts
2021
Rossi, Stefano | Buccarello, Andrea | Caffarra Malvezzi, Cristina | Pinelli, Silvana | Alinovi, Rossella | Guerrero Gerboles, Amparo | Rozzi, Giacomo | Leonardi, Fabio | Bollati, Valentina | De Palma, Giuseppe | Lagonegro, Paola | Rossi, F. (Francesca) | Lottici, Pier Paolo | Poli, Diana | Statello, Rosario | Macchi, Emilio | Miragoli, Michele
Air pollution is well recognized as a central player in cardiovascular disease. Exhaust particulate from diesel engines (DEP) is rich in nanoparticles and may contribute to the health effects of particulate matter in the environment. Moreover, diesel soot emitted by modern engines denotes defective surfaces alongside chemically-reactive sites increasing soot cytotoxicity. We recently demonstrated that engineered nanoparticles can cross the air/blood barrier and are capable to reach the heart. We hypothesize that DEP nanoparticles are pro-arrhythmogenic by direct interaction with cardiac cells. We evaluated the internalization kinetics and the effects of DEP, collected from Euro III (DEPe3, in the absence of Diesel Particulate Filter, DPF) and Euro IV (DEPe4, in the presence of DPF) engines, on alveolar and cardiac cell lines and on in situ rat hearts following DEP tracheal instillation. We observed significant differences in DEP size, metal and organic compositions derived from both engines. DEPe4 comprised ultrafine particles (<100 nm) and denoted a more pronounced toxicological outcome compared to DEPe3. In cardiomyocytes, particle internalization is fastened for DEPe4 compared to DEPe3. The in-vivo epicardial recording shows significant alteration of EGs parameters in both groups. However, the DEPe4-instilled group showed, compared to DEPe3, a significant increment of the effective refractory period, cardiac conduction velocity, and likelihood of arrhythmic events, with a significant increment of membrane lipid peroxidation but no increment in inflammation biomarkers. Our data suggest that DEPe4, possibly due to ultrafine nanoparticles, is rapidly internalized by cardiomyocytes resulting in an acute susceptibility to cardiac electrical disorder and arrhythmias that could accrue from cellular toxicity. Since the postulated transfer of nanoparticles from the lung to myocardial cells has not been investigated it remains open whether the effects on the cardiovascular function are the result of lung inflammatory reactions or due to particles that have reached the heart.
Show more [+] Less [-]New insights into cardiotoxicity induced by chiral fluoxetine at environmental-level: Enantioselective arrhythmia in developmental zebrafish (Danio rerio)
2021
Chai, Tingting | Cui, Feng | Di, Shanshan | Wu, Shenggan | Zhang, Yiming | Wang, Xinquan
Fluoxetine is frequently detected in aquatic environment, and chronic FLX exposure exhibits adverse effects on aquatic communities. Its chirality makes the adverse effects more complicated. This study aimed at the enantioselective cardiotoxicity in developmental zebrafish induced by racemic (rac-)/S-/R-fluoxetine. The accumulation profiles demonstrated that biotransformation of fluoxetine to norfluoxetine occurred during rac-fluoxetine exposure, with a higher enrichment of S-norfluoxetine than R-norfluoxetine. Heart malformations including pericardial edema, circulation abnormalities, and thrombosis were observed, and enantioselective changes also occurred. According to H&E staining and Masson’s trichrome staining, the loose severity of cardiac structure and cardiac fibrosis in rac-norfluoxetine treated group was worse than that in fluoxetine treated groups. Results of toxicity-associated parameters in our homochiral enantiomers’ exposure also indicated that the toxicity induced by S-fluoxetine was more severe than R-fluoxetine. Enantioselective arrhythmia in developmental zebrafish after chiral fluoxetine exposure could be caused by myocardial fibrosis, abnormal developmental processes, and the biotransformation of fluoxetine to norfluoxetine could make that worse. Our findings can be used to assess the environmental risk of the two enantiomers of fluoxetine that induce cardiotoxicity in aquatic organisms.
Show more [+] Less [-]Ozone and cardiac arrest: The role of previous hospitalizations
2019
Raza, Auriba | Dahlquist, Marcus | Jonsson, Martin | Hollenberg, Jacob | Svensson, S. Leif | Lind, Tomas | Ljungman, Petter L.S.
Several studies have reported associations between exposure to particulate matter and incidence of out-of-hospital cardiac arrest (OHCA) and some have observed associations with ozone (O3). There are no studies investigating susceptibility based on previous disease history to short-term O3 exposure and the risk of OHCA.To investigate the role of previous cardiovascular-related hospitalizations in modifying the associations between the risk of OHCA and short-term increase in O3 concentrations.A time-stratified case-crossover analysis of 11,923 OHCA registered in the Swedish Register for Cardiopulmonary Resuscitation from 2006 to 2014 was performed. Using personal identification numbers, OHCA were linked to all previous hospitalizations in Sweden since 1987 to create susceptible groups based on the principal diagnosis code at discharge. Susceptibility was based on hospitalization for i) acute myocardial infarction; ii) heart failure; iii) arrhythmias; iv) diabetes; v) hypertension; and vi) stroke. Moving 2 and 24-h averages for O3, PM2.5, PM10, and NO2 were constructed from hourly averages.A 10 μg/m3 higher 2-h average O3 concentration was associated with a 2% higher risk of OHCA (95% CI, 0% 3%). Associations were similar for 24-h average O3 and in individuals with or without hospitalizations for AMI, heart failure, diabetes, hypertension or stroke. Individuals with previous hospitalizations for arrhythmias had a lower risk of OHCA with higher O3. No associations were observed for other pollutants.Short-term exposure to O3 was associated with an elevated risk of OHCA, however, previous hospitalizations for cardiovascular diseases were not associated with additionally augmented risks.
Show more [+] Less [-]Assessment of raw and ozonated oil sands process-affected water exposure in developing zebrafish: Associating morphological changes with gene expression
2018
Lyons, Danielle D. | Philibert, Danielle A. | Zablocki, Taylor | Qin, Rui | Huang, Rongfu | Gamal El-Din, Mohamed | Tierney, Keith B.
With the ever-increasing amounts of oil sands process-affected water (OSPW) accumulating from Canada's oil sands operations, its eventual release must be considered. As OSPW has been found to be both acutely and chronically toxic to aquatic organisms, remediation processes must be developed to lower its toxicity. Ozone treatment is currently being studied as a tool to facilitate the removal of organic constituents associated with toxicity. Biomarkers (e.g. gene expression) are commonly used when studying the effects of environmental contaminants, however, they are not always indicative of adverse effects at the whole organism level. In this study, we assessed the effects of OSPW exposure on developing zebrafish by linking gene expression to relevant cellular and whole organism level endpoints. We also investigated whether or not ozone treatment decreased biomarkers and any associated toxicity observed from OSPW exposure. The concentrations of classical naphthenic acids in the raw and ozonated OSPW used in this study were 16.9 mg/L and 0.6 mg/L, respectively. Ozone treatment reduced the total amount of naphthenic acids (NAs) in the OSPW sample by 92%. We found that exposure to both raw and ozonated OSPW had no effect on the survival of zebrafish embryos. The expression levels of biotransformation genes CYP1A and CYP1B were induced by raw OSPW exposure, with CYP1B being more highly expressed than CYP1A. In contrast, ozonated OSPW exposure did not increase the expression of CYP1A and only slightly induced CYP1B. A decrease in cardiac development and function genes (NKX2.5 and APT2a2a) was not associates with large changes in heart rate, arrhythmia or heart size. We did not find any indications of craniofacial abnormalities or of increased occurrence of apoptotic cells. Overall, our study found that OSPW was not overtly toxic to zebrafish embryos.
Show more [+] Less [-]Temperature variability and hospitalization for cardiac arrhythmia in Brazil: A nationwide case-crossover study during 2000–2015
2019
Zhao, Qi | Coelho, Micheline S.Z.S. | Li, Shanshan | Saldiva, Paulo H.N. | Hu, Kejia | Abramson, Michael J. | Huxley, Rachel R. | Guo, Yuming
There is growing recognition of a potential role for environmental and climatic factors in influencing cardiovascular risk. It has been speculated that temperature variability (TV) is a risk factor for cardiac arrhythmia but evidence is limited.To quantify the geographic and demographic variations in the association between TV and hospitalization for cardiac arrhythmia in Brazil during 2000–2015.Data on hospitalization for arrhythmia and weather conditions were collected from 1,814 cities. TV was calculated as the standard deviation of daily maximum and minimum temperatures during exposure days. A time-stratified case-crossover approach was applied to examine the city-specific association between TV and hospitalization for arrhythmia. City-specific estimates were pooled at the national and regional levels using a random-effect meta-analysis. Stratified analyses were conducted by sex, three age-groups (0–64, 65–74 and ≥75 years), and three arrhythmia subtypes (paroxysmal tachycardia, atrial fibrillation and flutter, and other arrhythmias).There were 447,667 arrhythmia-related hospitalizations during 2000–2015. The odds ratio of hospitalization per 1 °C increase in TV peaked on 0–1 days’ exposure [1.012 (95% confidence interval: 1.010–1.015)]. There were no substantial differences in effect estimates of TV₀₋₁ by region, age or sex, except for the non-significant association observed in the north. However, women were more affected by prolonged TV exposure than men. For the three arrhythmias subtypes, only paroxysmal tachycardia and other arrhythmias were sensitive to TV. Assuming a causal relationship, 35,813 (95%CI: 18,302−51,665) cases were attributable to TV₀₋₁ in Brazil during 2000–2015, accounting for 8.0% (95%CI: 4.1–11.5%) of hospitalizations for cardiac arrhythmia.At a population-level exposure to TV was associated with increased risk of arrhythmia-related hospitalization in Brazil, with the relationship equally distributed across most residents but varied by arrhythmia subtypes. Our findings add to the accumulating evidence-base that climatic factors can influence cardiovascular outcomes in populations.
Show more [+] Less [-]Triggering of cardiovascular hospital admissions by fine particle concentrations in New York state: Before, during, and after implementation of multiple environmental policies and a recession
2018
Zhang, Wangjian | Lin, Shao | Hopke, Philip K. | Thurston, Sally W. | van Wijngaarden, Edwin | Croft, Daniel | Squizzato, Stefania | Masiol, Mauro | Rich, David Q.
Previous studies reported triggering of acute cardiovascular events by short-term increasedPM₂.₅ concentrations. From 2007 to 2013, national and New York state air quality policies and economic influences resulted in reduced concentrations of PM₂.₅ and other pollutants across the state. We estimated the rate of cardiovascular hospital admissions associated with increased PM₂.₅ concentrations in the previous 1–7 days, and evaluated whether they differed before (2005–2007), during (2008–2013), and after these concentration changes (2014–2016).Using the Statewide Planning and Research Cooperative System (SPARCS) database, we retained all hospital admissions with a primary diagnosis of nine cardiovascular disease (CVD) subtypes, for residents living within 15 miles of PM₂.₅ monitoring sites in Buffalo, Rochester, Albany, Queens, Bronx, and Manhattan from 2005 to 2016 (N = 1,922,918). We used a case-crossover design and conditional logistic regression to estimate the admission rate for total CVD, and nine specific subtypes, associated with increased PM₂.₅ concentrations.Interquartile range (IQR) increases in PM₂.₅ on the same and previous 6 days were associated with 0.6%–1.2% increases in CVD admission rate (2005–2016). There were similar patterns for cardiac arrhythmia, ischemic stroke, congestive heart failure, ischemic heart disease (IHD), and myocardial infarction (MI). Ambient PM₂.₅ concentrations and annual total CVD admission rates decreased across the period. However, the excess rate of IHD admissions associated with each IQR increase in PM₂.₅ in previous 2 days was larger in the after period (2.8%; 95%CI = 1.5%–4.0%) than in the during (0.6%; 95%CI = 0.0%–1.2%) or before periods (0.8%; 95%CI = 0.2%–1.3%), with similar patterns for total CVD and MI, but not other subtypes.While pollutant concentrations and CVD admission rates decreased after emission changes, the same PM₂.₅ mass was associated with a higher rate of ischemic heart disease events. Future work should confirm these findings in another population, and investigate whether specific PM components and/or sources trigger IHD events.
Show more [+] Less [-]Impact of ambient fine particulate matter on emergency department admissions for circulatory system disease in a city in Northeast China
2021
Zhao, Chenkai | Li, Qidian | Cui, Zhongming | Wang, JunLong | Sun, Li | Yin, Yan
The cardiovascular impact of fine particles has caused great concern worldwide. However, evidences on the impact of fine particulate matter (PM₂.₅) on emergency department (ED) admissions for circulatory system disease in Northeast China is limited. We assessed the acute, lag, cumulative, and harvesting effects of PM₂.₅ on ED admissions for circulatory system diseases and their exposure-response relationship. A total of 26,168 ED admissions, including those for hypertension, ischemic heart disease (IHD), arrhythmia, heart failure (HF), and cerebrovascular events (CVE), were collected from the Shenyang Emergency Center from 1 January 2017 to 31 December 2018. The relationship between PM₂.₅ and ED admissions for circulatory system disease was estimated using a distributed lag non-linear model and a generalized additive quasi-Poisson model. We stratified the analyses by temperature. Air pollution was positively correlated with daily ED admissions for circulatory system disease or other cause-specific diseases under different lag structures. For every 10-μg/m³ increase in the PM₂.₅ concentration, the relative risk of daily ED admissions for circulatory system disease was 1.007 [95% confidence interval (CI), 1.001–1.013] in lag0, 1.007 (95%CI, 1.000–1.013) in lag1, and 1.011 (95%CI, 1.002–1.021) in lag03. A lag effect was found in IHD, a cumulative effect was found in CVE, and both lag and cumulative effects were found in hypertension and arrhythmia. A harvesting effect was observed in daily ED admissions for circulatory system disease and HF. We found no interaction between pollutants and temperature. We observed a monotonic and almost linear exposure-response relationship between PM₂.₅ and circulatory system disease with no threshold effect.PM₂.₅ contributes to obvious acute, lag, cumulative, and harvesting effects on circulatory system disease. PM₂.₅ was associated with the risk of daily ED admissions for circulatory system disease, hypertension, IHD, arrhythmia, HF, and CVE. Therefore, air quality management must be strengthened.
Show more [+] Less [-]Individual PM2.5 exposure is associated with the impairment of cardiac autonomic modulation in general residents
2016
Xie, Yuquan | Bo, Liang | Jiang, Shuo | Tian, Zhenyong | Kan, Haidong | Yigang, | Song, Weimin | Zhao, Jinzhuo
Fine particulate matter (PM₂.₅) is one of the major pollutants in metropolitan areas. The current study was conducted to observe the effects of PM₂.₅ on cardiac autonomic modulation. The participants included 619 men and women aged from 35–75 in a residential area in Shanghai, China. All the participants were divided into four categories according to the distance between their apartments and major road. In addition, individual PM₂.₅ was measured using SIDEPAKTM AM510 (TSI, USA) from 8:00 am to 6:00 pm. At the end of the individual PM₂.₅ measurement, the systolic pressure, diastolic pressure, heart rate (HR), low-frequency (LF), high-frequency (HF), and LF/HF were determined. The association between individual PM₂.₅ level and the above health effects was analyzed using generalized linear regression. The results showed that the average concentration of individual PM₂.₅ was 95.5 and 87.0 μg/m³ for men and women. Residential distance to major road was negatively correlated with the individual PM₂.₅. The results indicated that per 1.0 μg/m³ increase of individual PM₂.₅ was associated with a 2.3 % increase for systolic pressure, 0.3 % increase for diastolic pressure, 0.4 % decrease for LF, and 0.4 % decrease for HF. Nevertheless, there was no statistical association between individual PM₂.₅ and heart rate and LF/HF in the total model. In addition, the similar results were found in men and women excluding a significant association between PM₂.₅ and the heart rate in men. The alterations of cardiac autonomic modulation hinted that PM₂.₅ exposure might be associated with the potential occurrence of cardiovascular disease, such as arrhythmia and ischemic heart diseases.
Show more [+] Less [-]Gallic acid protects particulate matter (PM10) triggers cardiac oxidative stress and inflammation causing heart adverse events in rats
2019
Radan, Maryam | Dianat, Mahin | Badavi, Mohammad | Mard, Seyyed Ali | Bayati, Vahid | Goudarzi, Gholamreza
Previous studies have shown that exposure to particulate matter (PM) increased variety of health problems, particularly cardiovascular diseases leading to premature mortality. The cardiac effects of particulate matter containing PM₁₀ include increased infarct size, decreased heart function, and increased arrhythmias in experimental ischemia-reperfusion models in rats. The aim of this study was to evaluate the effects of particles with an aerodynamic diameter smaller than 10 μm (PM₁₀) on isolated-rat heart and also to determine the efficacy of gallic acid (GA) as a preventive agent in oxidative damage. The healthy rats were divided into 8 equal groups which served as, control, GA, PM₁₀ (0.5, 2.5, and 5 mg/kg), and PM₁₀+GA groups. PM₁₀ administered into the lungs via the trachea in two stages with 48-h interval. After all experiments, the electrocardiogram was recorded. Then, the hemodynamic parameters and ventricular arrhythmias in rat isolated-hearts were assessed using Langendorff apparatus and according to the Lambeth conventions. In addition, the inflammation and oxidative stress factors in cardiac tissues were evaluated in all groups. The obtained results showed that the exposure to PM caused to decrease in cardiac hemodynamic and electrocardiogram parameters. Also, in PM₁₀ rat groups, the IL-6, TNF-α, and oxidative stress parameters were increased. Gallic acid preserved the value of cardiac parameters and inflammation in rat hearts. In summary, we added a novel therapeutic effect of gallic acid for cardiac dysfunction induced by particulate matter. These findings could be related to antioxidant and antiinflammation properties and the obtained results suggest that natural antioxidant like gallic acid could be a therapeutic agent in prevention and management of health issues in the polluted areas of the world.
Show more [+] Less [-]The effects of PM10 on electrocardiogram parameters, blood pressure and oxidative stress in healthy rats: the protective effects of vanillic acid
2016
Dianat, Mahin | Radmanesh, Esmat | Badavi, Mohammad | Goudarzi, Gholamreza | Mard, Seyyed Ali
Particulate matter (PM) inhalation is an established trigger of cardiovascular events such as cardiac arrhythmias that occur within hours to days after exposure. Higher daily PM levels are related to acute increases in systemic arterial blood pressure (BP). The aim of the present study was to evaluate the effects of PM₁₀ on electrocardiogram (ECG) parameters, blood pressure, lipid peroxidation (MDA), xanthine oxidase, and antioxidant enzyme in healthy rats and also to examine the protective effects of vanillic acid (VA) in this respect. Eighty male Wistar rats were divided into eight groups (n = 10), namely control (normal saline, gavage), VAc (10 mg/kg), sham (normal saline, intratracheal instillation), VA (10 mg/kg VA, 10 days gavage +0.1 ml normal saline, intratracheal instillation), PM1 (0.5 mg/kg), PM2 (2.5 mg/kg), PM3 (5 mg/kg), PM3 + VA (5 mg/kg, intratracheal instillation + 10 mg/kg VA, 10 days, gavage) groups. The rats were anesthetized and 0.1 ml of saline as well as a certain concentration of PM₁₀ was instilled into the trachea and it was repeated after 48 h, then 30 min after that, PR interval, QTc, and systolic blood pressure were measured. The activities of antioxidant enzymes, xanthine oxidase (XOX), and malondialdehyde (MDA) were measured in plasma by special Kits. A significant increase in blood pressure (BP), PR interval, QTc, MDA, and XOX and a significant decrease in antioxidant enzyme (CAT, SOD, and GPx) occurred in PM₁₀ groups. Vanillic acid ameliorated blood pressure, QTc, PR interval, XOX, MDA, and increased antioxidant enzymes (SOD, CAT, and GPx) significantly. In the present study, it was shown that PM₁₀ had devastating effects on the heart and blood pressure, probably due to the increased oxidative stress in healthy rats. Vanillic acid could improve the symptoms of PM₁₀ exposure and can be used as an antioxidant agent against the harmful effects of PM₁₀.
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