| 1. |
- Barath, Stefan, et al.
(författare)
-
Impaired vascular function after exposure to diesel exhaust generated at urban transient running conditions
- 2010
-
Ingår i: Particle and Fibre Toxicology. - : BioMed Central. - 1743-8977. ; 7:1, s. 19-
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Traffic emissions including diesel engine exhaust are associated with increased respiratory and cardiovascular morbidity and mortality. Controlled human exposure studies have demonstrated impaired vascular function after inhalation of exhaust generated by a diesel engine under idling conditions.OBJECTIVES: To assess the vascular and fibrinolytic effects of exposure to diesel exhaust generated during urban-cycle running conditions that mimic ambient 'real-world' exposures.METHODS: In a randomised double-blind crossover study, eighteen healthy male volunteers were exposed to diesel exhaust (approximately 250 mug/m3) or filtered air for one hour during intermittent exercise. Diesel exhaust was generated during the urban part of the standardized European Transient Cycle. Six hours post-exposure, vascular vasomotor and fibrinolytic function was assessed during venous occlusion plethysmography with intra-arterial agonist infusions.MEASUREMENTS AND MAIN RESULTS: Forearm blood flow increased in a dose-dependent manner with both endothelial-dependent (acetylcholine and bradykinin) and endothelial-independent (sodium nitroprusside and verapamil) vasodilators. Diesel exhaust exposure attenuated the vasodilatation to acetylcholine (P < 0.001), bradykinin (P < 0.05), sodium nitroprusside (P < 0.05) and verapamil (P < 0.001). In addition, the net release of tissue plasminogen activator during bradykinin infusion was impaired following diesel exhaust exposure (P < 0.05).CONCLUSION: Exposure to diesel exhaust generated under transient running conditions, as a relevant model of urban air pollution, impairs vasomotor function and endogenous fibrinolysis in a similar way as exposure to diesel exhaust generated at idling. This indicates that adverse vascular effects of diesel exhaust inhalation occur over different running conditions with varying exhaust composition and concentrations as well as physicochemical particle properties. Importantly, exposure to diesel exhaust under ETC conditions was also associated with a novel finding of impaired of calcium channel-dependent vasomotor function. This implies that certain cardiovascular endpoints seem to be related to general diesel exhaust properties, whereas the novel calcium flux-related effect may be associated with exhaust properties more specific for the ETC condition, for example a higher content of diesel soot particles along with their adsorbed organic compounds.
|
|
| 2. |
- Barath, Stefan, 1963-, et al.
(författare)
-
Short-Term Exposure to Ozone Does Not Impair Vascular Function or Affect Heart Rate Variability in Healthy Young Men
- 2013
-
Ingår i: Toxicological Sciences. - : Oxford University Press. - 1096-6080 .- 1096-0929. ; 135:2, s. 292-299
-
Tidskriftsartikel (refereegranskat)abstract
- Air pollution exposure is associated with cardiovascular morbidity and mortality, yet the role of individual pollutants remains unclear. In particular, there is uncertainty regarding the acute effect of ozone exposure on cardiovascular disease. In these studies, we aimed to determine the effect of ozone exposure on vascular function, fibrinolysis, and the autonomic regulation of the heart. Thirty-six healthy men were exposed to ozone (300 ppb) and filtered air for 75min on two occasions in randomized double-blind crossover studies. Bilateral forearm blood flow (FBF) was measured using forearm venous occlusion plethysmography before and during intra-arterial infusions of vasodilators 2–4 and 6–8h after each exposure. Heart rhythm and heart rate variability (HRV) were monitored during and 24h after exposure. Compared with filtered air, ozone exposure did not alter heart rate, blood pressure, or resting FBF at either 2 or 6h. There was a dose-dependent increase in FBF with all vasodilators that was similar after both exposures at 2–4h. Ozone exposure did not impair vasomotor or fibrinolytic function at 6–8h but rather increased vasodilatation to acetylcholine (p = .015) and sodium nitroprusside (p = .005). Ozone did not affect measures of HRV during or after the exposure. Our findings do not support a direct rapid effect of ozone on vascular function or cardiac autonomic control although we cannot exclude an effect of chronic exposure or an interaction between ozone and alternative air pollutants that may be responsible for the adverse cardiovascular health effects attributed to ozone.
|
|
| 3. |
- Hunter, Amanda, et al.
(författare)
-
Effect of wood smoke exposure on vascular function and thrombus formation in healthy fire fighters
- 2014
-
Ingår i: Particle and Fibre Toxicology. - : BioMed Central (BMC). - 1743-8977. ; 11
-
Tidskriftsartikel (refereegranskat)abstract
- Background: Myocardial infarction is the leading cause of death in fire fighters and has been linked with exposure to air pollution and fire suppression duties. We therefore investigated the effects of wood smoke exposure on vascular vasomotor and fibrinolytic function, and thrombus formation in healthy fire fighters. Methods: In a double-blind randomized cross-over study, 16 healthy male fire fighters were exposed to wood smoke (~1 mg/m3 particulate matter concentration) or filtered air for one hour during intermittent exercise. Arterial pressure and stiffness were measured before and immediately after exposure, and forearm blood flow was measured during intra-brachial infusion of endothelium-dependent and -independent vasodilators 4–6 hours after exposure. Thrombus formation was assessed using the ex vivo Badimon chamber at 2 hours, and platelet activation was measured using flow cytometry for up to 24 hours after the exposure. Results: Compared to filtered air, exposure to wood smoke increased blood carboxyhaemoglobin concentrations (1.3% versus 0.8%; P < 0.001), but had no effect on arterial pressure, augmentation index or pulse wave velocity (P > 0.05 for all). Whilst there was a dose-dependent increase in forearm blood flow with each vasodilator (P < 0.01 for all), there were no differences in blood flow responses to acetylcholine, sodium nitroprusside or verapamil between exposures (P > 0.05 for all). Following exposure to wood smoke, vasodilatation to bradykinin increased (P = 0.003), but there was no effect on bradykinin-induced tissue-plasminogen activator release, thrombus area or markers of platelet activation (P > 0.05 for all). Conclusions: Wood smoke exposure does not impair vascular vasomotor or fibrinolytic function, or increase thrombus formation in fire fighters. Acute cardiovascular events following fire suppression may be precipitated by exposure to other air pollutants or through other mechanisms, such as strenuous physical exertion and dehydration.
|
|
| 4. |
- Langrish, Jeremy P, et al.
(författare)
-
Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man
- 2013
-
Ingår i: Journal of the American Heart Association. - : American stroke association. - 2047-9980 .- 2047-9980. ; 2:1, s. e004309-
-
Tidskriftsartikel (refereegranskat)abstract
- Background Diesel exhaust inhalation causes cardiovascular dysfunction including impaired vascular reactivity, increased blood pressure, and arterial stiffness. We investigated the role of nitric oxide (NO) bioavailability in mediating these effects.Methods and Results In 2 randomized double-blind crossover studies, healthy nonsmokers were exposed to diesel exhaust or filtered air. Study 1: Bilateral forearm blood flow was measured during intrabrachial infusions of acetylcholine (ACh; 5 to 20 mu g/min) and sodium nitroprusside (SNP; 2 to 8 mu g/min) in the presence of the NO clamp (NO synthase inhibitor N-G-monomethyl-L-arginine (L-NMMA) 8 mu g/min coinfused with the NO donor SNP at 90 to 540 ng/min to restore basal blood flow). Study 2: Blood pressure, arterial stiffness, and cardiac output were measured during systemic NO synthase inhibition with intravenous L-NMMA (3 mg/kg). Following diesel exhaust inhalation, plasma nitrite concentrations were increased (68 +/- 48 versus 41 +/- 32 nmol/L; P=0.006) despite similar L-NMMA-induced reductions in basal blood flow (-20.6 +/- 14.7% versus -21.1 +/- 14.6%; P=0.559) compared to air. In the presence of the NO clamp, ACh and SNP caused dose-dependent vasodilatation that was not affected by diesel exhaust inhalation (P>0.05 for both). Following exposure to diesel exhaust, L-NMMA caused a greater increase in blood pressure (P=0.048) and central arterial stiffness (P=0.007), but reductions in cardiac output and increases in systemic vascular resistance (P>0.05 for both) were similar to those seen with filtered air.Conclusions Diesel exhaust inhalation disturbs normal vascular homeostasis with enhanced NO generation unable to compensate for excess consumption. We suggest the adverse cardiovascular effects of air pollution are, in part, mediated through reduced NO bioavailability.
|
|
| 5. |
|
|
| 6. |
- Langrish, Jeremy P., et al.
(författare)
-
Controlled exposures to air pollutants and risk of cardiac arrhythmia
- 2014
-
Ingår i: Journal of Environmental Health Perspectives. - : Environmental Health Perspectives. - 0091-6765 .- 1552-9924. ; 122:7, s. 747-753
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Epidemiological studies have reported associations between air pollution exposure and increases in cardiovascular morbidity and mortality. Exposure to air pollutants can influence cardiac autonomic tone and reduce heart rate variability, and may increase the risk of cardiac arrhythmias, particularly in susceptible patient groups. OBJECTIVES: We investigated the incidence of cardiac arrhythmias during and after controlled exposure to air pollutants in healthy volunteers and patients with coronary heart disease. METHODS: We analyzed data from 13 double-blind randomized crossover studies including 282 participants (140 healthy volunteers and 142 patients with stable coronary heart disease) from whom continuous electrocardiograms were available. The incidence of cardiac arrhythmias was recorded for each exposure and study population. RESULTS: There were no increases in any cardiac arrhythmia during or after exposure to dilute diesel exhaust, wood smoke, ozone, concentrated ambient particles, engineered carbon nanoparticles, or high ambient levels of air pollution in either healthy volunteers or patients with coronary heart disease. CONCLUSIONS: Acute controlled exposure to air pollutants did not increase the short-term risk of arrhythmia in participants. Research employing these techniques remains crucial in identifying the important pathophysiological pathways involved in the adverse effects of air pollution, and is vital to inform environmental and public health policy decisions.
|
|
| 7. |
- Lucking, Andrew J, et al.
(författare)
-
Particle traps prevent adverse vascular and prothrombotic effects of diesel engine exhaust inhalation in men
- 2011
-
Ingår i: Circulation. - 0009-7322 .- 1524-4539. ; 123:16, s. 1721-1728
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: In controlled human exposure studies, diesel engine exhaust inhalation impairs vascular function and enhances thrombus formation. The aim of the present study was to establish whether an exhaust particle trap could prevent these adverse cardiovascular effects in men. METHODS AND RESULTS: Nineteen healthy volunteers (mean age, 25±3 years) were exposed to filtered air and diesel exhaust in the presence or absence of a particle trap for 1 hour in a randomized, double-blind, 3-way crossover trial. Bilateral forearm blood flow and plasma fibrinolytic factors were assessed with venous occlusion plethysmography and blood sampling during intra-arterial infusion of acetylcholine, bradykinin, sodium nitroprusside, and verapamil. Ex vivo thrombus formation was determined with the use of the Badimon chamber. Compared with filtered air, diesel exhaust inhalation was associated with reduced vasodilatation and increased ex vivo thrombus formation under both low- and high-shear conditions. The particle trap markedly reduced diesel exhaust particulate number (from 150 000 to 300 000/cm(3) to 30 to 300/cm(3); P<0.001) and mass (320±10 to 7.2±2.0 μg/m(3); P<0.001), and was associated with increased vasodilatation, reduced thrombus formation, and an increase in tissue-type plasminogen activator release. CONCLUSIONS: Exhaust particle traps are a highly efficient method of reducing particle emissions from diesel engines. With a range of surrogate measures, the use of a particle trap prevents several adverse cardiovascular effects of exhaust inhalation in men. Given these beneficial effects on biomarkers of cardiovascular health, the widespread use of particle traps on diesel-powered vehicles may have substantial public health benefits and reduce the burden of cardiovascular disease.
|
|
| 8. |
- Mills, Nicholas L, et al.
(författare)
-
Diesel exhaust inhalation does not affect heart rhythm or heart rate variability
- 2011
-
Ingår i: Heart. - : BMJ. - 1355-6037 .- 1468-201X. ; 97:7, s. 544-550
-
Tidskriftsartikel (refereegranskat)abstract
- Objective Exposure to air pollution is associated with increases in cardiovascular morbidity and mortality. This study was undertaken to determine the effect of diesel exhaust inhalation on heart rhythm and heart rate variability in healthy volunteers and patients with coronary heart disease.Design and setting Double-blind randomised crossover studies in a university teaching hospital.Patients 32 healthy non-smoking volunteers and 20 patients with prior myocardial infarction.Interventions All 52 subjects were exposed for 1 h to dilute diesel exhaust (particle concentration 300 μg/m(3)) or filtered air.Main outcome measures Heart rhythm and heart rate variability were monitored during and for 24 h after the exposure using continuous ambulatory electrocardiography and assessed using standard time and frequency domain analysis.Results No significant arrhythmias occurred during or following exposures. Patients with coronary heart disease had reduced autonomic function in comparison to healthy volunteers, with reduced standard deviations of the NN interval (SDNN, p<0.001) and triangular index (p<0.001). Diesel exhaust did not affect heart rate variability compared with filtered air (p>0.05 for all) in healthy volunteers (SDNN 101±6 vs 91±6, triangular index 20±1 vs 21±1) or patients with coronary heart disease (SDNN 47±5 vs 38±4, triangular index 8±1 vs 7±1).Conclusions Brief exposure to dilute diesel exhaust does not alter heart rhythm or heart rate variability in healthy volunteers or well-treated patients with stable coronary heart disease. Autonomic dysfunction does not appear to be a dominant mechanism that can explain the observed excess in cardiovascular events following exposure to combustion-derived air pollution.
|
|
| 9. |
- Muala, Ala, et al.
(författare)
-
Assessment of the capacity of vehicle cabin air inlet filters to reduce diesel exhaust-induced symptoms in human volunteers
- 2014
-
Ingår i: Environmental Health. - : BioMed Central (BMC). - 1476-069X. ; 13:1
-
Tidskriftsartikel (refereegranskat)abstract
- BACKGROUND: Exposure to particulate matter (PM) air pollution especially derived from traffic is associated with increases in cardiorespiratory morbidity and mortality. In this study, we evaluated the ability of novel vehicle cabin air inlet filters to reduce diesel exhaust (DE)-induced symptoms and markers of inflammation in human subjects.METHODS: Thirty healthy subjects participated in a randomized double-blind controlled crossover study where they were exposed to filtered air, unfiltered DE and DE filtered through two selected particle filters, one with and one without active charcoal. Exposures lasted for one hour. Symptoms were assessed before and during exposures and lung function was measured before and after each exposure, with inflammation assessed in peripheral blood five hours after exposures. In parallel, PM were collected from unfiltered and filtered DE and assessed for their capacity to drive damaging oxidation reactions in a cell-free model, or promote inflammation in A549 cells.RESULTS: The standard particle filter employed in this study reduced PM10 mass concentrations within the exposure chamber by 46%, further reduced to 74% by the inclusion of an active charcoal component. In addition use of the active charcoal filter was associated by a 75% and 50% reduction in NO2 and hydrocarbon concentrations, respectively. As expected, subjects reported more subjective symptoms after exposure to unfiltered DE compared to filtered air, which was significantly reduced by the filter with an active charcoal component. There were no significant changes in lung function after exposures. Similarly diesel exhaust did not elicit significant increases in any of the inflammatory markers examined in the peripheral blood samples 5 hour post-exposure. Whilst the filters reduced chamber particle concentrations, the oxidative activity of the particles themselves, did not change following filtration with either filter. In contrast, diesel exhaust PM passed through the active charcoal combination filter appeared less inflammatory to A549 cells.CONCLUSIONS: A cabin air inlet particle filter including an active charcoal component was highly effective in reducing both DE particulate and gaseous components, with reduced exhaust-induced symptoms in healthy volunteers. These data demonstrate the effectiveness of cabin filters to protect subjects travelling in vehicles from diesel exhaust emissions.
|
|
| 10. |
- Unosson, Jon, 1980-
(författare)
-
Acute cardiovascular effects of biofuel exhaust exposure
- 2014
-
Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- BackgroundAnthropogenic air pollution is a global health problem estimated to contribute to millions of premature deaths. Exposure to biomass smoke is common due to varying sources, such as wildfires, indoor cooking over open fires, and residential heating from wood stoves. In urban environments transportation and industry rely heavily on the combustion of fossil fuels yet environmental policies increasingly support a shift to renewable fuels such as biodiesel. It has not been investigated how either wood smoke or biodiesel exhaust affect human health in general or the cardiovascular system in particular. We hypothesized that wood smoke exposure would induce acute cardiovascular impairment via similar underlying mechanisms as have been established for petrodiesel exhaust exposure. We also hypothesized that replacing petrodiesel with biodiesel, as a blend or pure biodiesel, would generate an exhaust profile with a less harmful effect on the cardiovascular system than petrodiesel exhaust.MethodsIn four separate studies healthy non-smoking subjects were exposed to different air pollutants in controlled exposure chambers followed by clinical investigations of the cardiovascular system. All studies were performed as randomized controlled trials in a crossover fashion with each individual acting as her own control. In study I healthy volunteers were exposed to wood smoke at a target concentration of particulate matter (PM) 300 µg/m3 for three hours followed by measures of blood pressure, heart rate variability and central arterial stiffness. In study II subjects were exposed to wood smoke at a target concentration of PM 1000 µg/m3 for one hour followed by measures of thrombus formation using the Badimon technique and vasomotor function using forearm venous occlusion plethysmography. In study III subjects were exposed to petrodiesel exhaust and a 30% rapeseed methyl ester (RME30) biodiesel blend for one hour at a target concentration of PM 300 µg/m3. Following exposure, thrombus formation and vasomotor function were assessed as in study II. In study IV subjects were exposed to petrodiesel exhaust at a target concentration of PM 300 μg/m3for one hour and pure rapeseed methyl ester (RME100) exhaust generated at identical running conditions of the engine. Following exposure, thrombus formation and vasomotor function were assessed as in study II and III.ResultsIn study I fourteen subjects (8 males) were exposed to wood smoke at P M 294±36 μg/m3. Compared to filtered air exposure, measures of central arterial stiffness were increased and heart rate variability was decreased following wood smoke exposure. No effect was seen on blood pressure. In study II sixteen males were exposed to wood smoke at PM 899±100 μg/m3. We found no evidence of increased thrombus formation or impaired vasomotor function following wood smoke exposure. In study III sixteen subjects (14 males) were exposed to petrodiesel exhaust (PM 314±27 µg/m3) and RME30 exhaust (PM 309±30 µg/m3). Thrombus formation and vasomotor function were equal following either exposure. In study IV nineteen males were exposed to petrodiesel exhaust (PM 310±34 µg/m3, 1.7±0.3 x105 particles/cm3) and RME100 exhaust (PM 165±16 µg/m3, 2.2±0.1 x105 particles/cm3). As in study III, thrombus formation and vasomotor function were identical following both exposures.ConclusionsWe have for the first time demonstrated that wood smoke exposure can increase central arterial stiffness and decrease heart rate variability in healthy subjects. We did not, however find evidence of increased thrombus formation and impaired vasomotor function following wood smoke exposure at a higher concentration for a shorter time period. We have, for the first time, demonstrated that exhaust from RME biodiesel induced acute adverse cardiovascular effects of increased thrombus formation and impaired vasomotor function in man. These effects are on par with those seen following exposure to petrodiesel exhaust, despite marked physicochemical differences of the exhaust characteristics.
|
|
