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An autonomic link between inhaled diesel exhaust and impaired cardiac performance: insight from treadmill and dobutamine challenges in heart failure-prone rats.

ABSTRACT: Cardiac disease exacerbation is associated with short-term exposure to vehicular emissions. Diesel exhaust (DE) might impair cardiac performance in part through perturbing efferent sympathetic and parasympathetic autonomic nervous system (ANS) input to the heart. We hypothesized that acute changes in ANS balance mediate decreased cardiac performance upon DE inhalation. Young adult heart failure-prone rats were implanted with radiotelemeters to measure heart rate (HR), HR variability (HRV), blood pressure (BP), core body temperature, and pre-ejection period (PEP, a contractility index). Animals pretreated with sympathetic antagonist (atenolol), parasympathetic antagonist (atropine), or saline were exposed to DE (500 µg/m(3) fine particulate matter, 4h) or filtered air and then treadmill exercise challenged. At 1 day postexposure, separate rats were catheterized for left ventricular pressure (LVP), contractility, and lusitropy and assessed for autonomic influence using the sympathoagonist dobutamine and surgical vagotomy. During DE exposure, atenolol inhibited increases in HR, BP, and contractility, but not body temperature, suggesting a role for sympathetic dominance. During treadmill recovery at 4h post-DE exposure, HR and HRV indicated parasympathetic dominance in saline- and atenolol-pretreated groups that atropine inhibited. Conversely, at treadmill recovery 21h post-DE exposure, HRV and PEP indicated sympathetic dominance and subsequently diminished contractility that only atenolol inhibited. LVP at 1 day postexposure indicated that DE impaired contractility and lusitropy while abolishing parasympathetic-regulated cardiac responses to dobutamine. This is the first evidence that air pollutant inhalation both causes time-dependent oscillations between sympathetic and parasympathetic dominance and decreases cardiac performance via aberrant sympathetic dominance.

SUBMITTER: Carll AP

PROVIDER: S-EPMC3937599 | biostudies-literature | 2013 Oct

REPOSITORIES: biostudies-literature

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An autonomic link between inhaled diesel exhaust and impaired cardiac performance: insight from treadmill and dobutamine challenges in heart failure-prone rats.

Carll Alex P AP Hazari Mehdi S MS Perez Christina M CM Krantz Q Todd QT King Charly J CJ Haykal-Coates Najwa N Cascio Wayne E WE Costa Daniel L DL Farraj Aimen K AK

Toxicological sciences : an official journal of the Society of Toxicology 20130719 2

Cardiac disease exacerbation is associated with short-term exposure to vehicular emissions. Diesel exhaust (DE) might impair cardiac performance in part through perturbing efferent sympathetic and parasympathetic autonomic nervous system (ANS) input to the heart. We hypothesized that acute changes in ANS balance mediate decreased cardiac performance upon DE inhalation. Young adult heart failure-prone rats were implanted with radiotelemeters to measure heart rate (HR), HR variability (HRV), blood ...[more]

PMID: 23872579

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Project description:BACKGROUND:Exposure to air pollution impairs aspects of pulmonary and autonomic function and causes pulmonary inflammation. However, how exercising in air pollution affects these indices is poorly understood. Therefore, the purpose of this study was to determine the effects of low-intensity and high-intensity cycling with diesel exhaust (DE) exposure on pulmonary function, heart rate variability (HRV), fraction of exhaled nitric oxide (FeNO), norepinephrine and symptoms. METHODS:Eighteen males performed 30-min trials of low-intensity or high-intensity cycling (30 and 60% of power at VO2peak) or a resting control condition. For each subject, each trial was performed once breathing filtered air (FA) and once breathing DE (300?g/m3 of PM2.5, six trials in total). Pulmonary function, FeNO, HRV, norepinephrine and symptoms were measured prior to, immediately post, 1?h and 2?h post-exposure. Data were analyzed using repeated-measures ANOVA. RESULTS:Throat and chest symptoms were significantly greater immediately following DE exposure than following FA (p?<?0.05). FeNO significantly increased 1?h following high-intensity exercise in DE (21.9 (2.4) vs. 19.3 (2.2) ppb) and FA (22.7 (1.7) vs. 19.9 (1.4)); however, there were no differences between the exposure conditions. All HRV indices significantly decreased following high-intensity exercise (p?<?0.05) in DE and FA. The exception to this pattern was LF (nu) and LF/HF ratio, which significantly increased following high-intensity exercise (p?<?0.05). Plasma norepinephrine (NE) significantly increased following high-intensity exercise in DE and FA, and this increase was greater than following rest and low-intensity exercise (p?<?0.05). DE exposure did not modify any effects of exercise intensity on HRV or norepinephrine. CONCLUSIONS:Healthy individuals may not experience greater acute pulmonary and autonomic effects from exercising in DE compared to FA; therefore, it is unclear if such individuals will benefit from reducing vigorous activity on days with high concentrations on particulate matter.

Project description:BackgroundMost studies of the association between diesel exhaust exposure and lung cancer suggest a modest, but consistent, increased risk. However, to our knowledge, no study to date has had quantitative data on historical diesel exposure coupled with adequate sample size to evaluate the exposure-response relationship between diesel exhaust and lung cancer. Our purpose was to evaluate the relationship between quantitative estimates of exposure to diesel exhaust and lung cancer mortality after adjustment for smoking and other potential confounders.MethodsWe conducted a nested case-control study in a cohort of 12 315 workers in eight non-metal mining facilities, which included 198 lung cancer deaths and 562 incidence density-sampled control subjects. For each case subject, we selected up to four control subjects, individually matched on mining facility, sex, race/ethnicity, and birth year (within 5 years), from all workers who were alive before the day the case subject died. We estimated diesel exhaust exposure, represented by respirable elemental carbon (REC), by job and year, for each subject, based on an extensive retrospective exposure assessment at each mining facility. We conducted both categorical and continuous regression analyses adjusted for cigarette smoking and other potential confounding variables (eg, history of employment in high-risk occupations for lung cancer and a history of respiratory disease) to estimate odds ratios (ORs) and 95% confidence intervals (CIs). Analyses were both unlagged and lagged to exclude recent exposure such as that occurring in the 15 years directly before the date of death (case subjects)/reference date (control subjects). All statistical tests were two-sided.ResultsWe observed statistically significant increasing trends in lung cancer risk with increasing cumulative REC and average REC intensity. Cumulative REC, lagged 15 years, yielded a statistically significant positive gradient in lung cancer risk overall (P (trend) = .001); among heavily exposed workers (ie, above the median of the top quartile [REC ≥ 1005 μg/m(3)-y]), risk was approximately three times greater (OR = 3.20, 95% CI = 1.33 to 7.69) than that among workers in the lowest quartile of exposure. Among never smokers, odd ratios were 1.0, 1.47 (95% CI = 0.29 to 7.50), and 7.30 (95% CI = 1.46 to 36.57) for workers with 15-year lagged cumulative REC tertiles of less than 8, 8 to less than 304, and 304 μg/m(3)-y or more, respectively. We also observed an interaction between smoking and 15-year lagged cumulative REC (P (interaction) = .086) such that the effect of each of these exposures was attenuated in the presence of high levels of the other.ConclusionOur findings provide further evidence that diesel exhaust exposure may cause lung cancer in humans and may represent a potential public health burden.

Project description:BackgroundWith the exception of lung cancer, the health effects associated with diesel exhaust for other cancers and nonmalignant health outcomes are not well understood.ObjectivesWe extended the mortality follow-up of the Diesel Exhaust in Miners Study, a cohort study of 12,315 workers, by 18 y (ending 31 December 2015), more than doubling the number of observed deaths to n=4,887, to evaluate associations between mortality and diesel exhaust exposure.MethodsQuantitative estimates of historical exposure to respirable elemental carbon (REC), a surrogate for diesel exhaust, were created for all jobs, by year and facility, using measurements collected from each mine, as well as historical measurements. Standardized mortality ratios (SMRs) and hazard ratios (HRs) were estimated for the entire cohort and by worker location (surface, underground).ResultsWe observed an excess of death for cancers of the lung, trachea, and bronchus (n=409; SMR=1.24; 95% CI: 1.13, 1.37). Among workers who ever worked underground, where the majority of diesel exposure occurred, excess deaths were evident for lung, trachea, and bronchus cancers (n=266; SMR=1.26; 95% CI: 1.11, 1.42). Several nonmalignant diseases were associated with excess mortality among workers ever-employed underground, including ischemic heart disease (SMR=1.08; 95% CI: 1.00, 1.16), cerebrovascular disease (SMR=1.22; 95% CI: 1.04, 1.43), and nonmalignant diseases of the respiratory system (SMR=1.13; 95% CI: 1.01, 1.26). Continuous 15-y lagged cumulative REC exposure <1,280 μg/m3-y was associated with increased lung cancer risk (HR=1.93; 95% CI: 1.24, 3.03), but the risk declined at the highest exposures (HR=1.29; 95% CI: 0.74, 2.26). We also observed a significant trend in non-Hodgkin lymphoma (NHL) risk with increasing 20-y lagged cumulative REC (HRTertile3 vs. Tertile1=3.12; 95% CI: 1.00, 9.79; p-trend=0.031).DiscussionIncreased risks of lung cancer mortality observed in the original study were sustained. Observed associations between diesel exposure and risk of death from NHL and the excesses in deaths for diseases of the respiratory and cardiovascular system, including ischemic heart disease and cerebrovascular disease, warrant further study and provide evidence of the potential widespread public health impact of diesel exposure. https://doi.org/10.1289/EHP12840.

Project description:Allergen exposure and air pollution are two risk factors for asthma development and airway inflammation that have been examined extensively in isolation. The impact of combined allergen and diesel exhaust exposure has received considerably less attention. Diesel exhaust (DE) is a major contributor to ambient particulate matter (PM) air pollution, which can act as an adjuvant to immune responses and augment allergic inflammation. We aimed to clarify whether DE increases allergen-induced inflammation and cellular immune response in the airways of atopic human subjects.Twelve atopic subjects were exposed to DE 300 ?g.m(-3) or filtered air for 2 h in a blinded crossover study design with a four-week washout period between arms. One hour following either filtered air or DE exposure, subjects were exposed to allergen or saline (vehicle control) via segmental challenge. Forty-eight hours post-allergen or control exposure, bronchial biopsies were collected. The study design generated 4 different conditions: filtered air?+?saline (FAS), DE?+?saline (DES), filtered air?+?allergen (FAA) and DE?+?allergen (DEA). Biopsies sections were immunostained for tryptase, eosinophil cationic protein (ECP), neutrophil elastase (NE), CD138, CD4 and interleukin (IL)-4. The percent positivity of positive cells were quantified in the bronchial submucosa.The percent positivity for tryptase expression and ECP expression remained unchanged in the bronchial submucosa in all conditions. CD4 % positive staining in DEA (0.311?±?0.060) was elevated relative to FAS (0.087?±?0.018; p?=?0.035). IL-4% positive staining in DEA (0.548?±?0.143) was elevated relative to FAS (0.127?±?0.062; p?=?0.034). CD138 % positive staining in DEA (0.120?±?0.031) was elevated relative to FAS (0.017?±?0.006; p?=?0.015), DES (0.044?±?0.024; p?=?0.040), and FAA (0.044?±?0.008; p?=?0.037). CD138% positive staining in FAA (0.044?±?0.008) was elevated relative to FAS (0.017?±?0.006; p?=?0.049). NE percent positive staining in DEA (0.224?±?0.047) was elevated relative to FAS (0.045?±?0.014; p?=?0.031).In vivo allergen and DE co-exposure results in elevated CD4, IL-4, CD138 and NE in the respiratory submucosa of atopic subjects, while eosinophils and mast cells are not changed.URL: http://www.clinicaltrials.gov. Unique identifier: NCT01792232.

Dataset Information

An autonomic link between inhaled diesel exhaust and impaired cardiac performance: insight from treadmill and dobutamine challenges in heart failure-prone rats.

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An autonomic link between inhaled diesel exhaust and impaired cardiac performance: insight from treadmill and dobutamine challenges in heart failure-prone rats.

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