umu.sePublications
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Cardiovascular effects of diesel exhaust: mechanistic and interventional studies
Umeå University, Faculty of Medicine, Department of Public Health and Clinical Medicine, Pulmonary Medicine. (Lungmedicin)
2009 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Background: Air pollution is associated with negative health effects. Exposure to combustion-derived particulate matter (PM) air pollution has been related to increased incidence of cardiovascular and respiratory morbidity and mortality, specifically in susceptible populations. Ambient particles, with a diameter of less than 2.5 mm, have been suggested to be the strongest contributor to these health effects. Diesel exhaust (DE) is a major source of small combustion-derived PM air pollution world wide. 

In healthy volunteers, exposure to DE, has been associated with airway inflammation and impaired vasomotor function and endogenous fibrinolysis.

The aims of this thesis were to further elucidate the underlying mechanisms to the reported cardiovascular effects following exposure to DE, with specific focus on endothelin-1 (ET-1). Additionally, the vascular effects of the major gaseous component of DE, nitrogen dioxide (NO2), were assessed together with the impact of an exhaust particle trap to reduce the observed negative vascular effects after DE exposure.

Methods: In all studies healthy, non-smoking male volunteers were included and exposed for one hour during intermittent exercise in a randomised double-blind crossover fashion. In studies I-III, subjects were exposed to DE at a particulate matter concentration of approximately 300 μg/m3 and filtered air, on two different occasions. In study V an additional exposure was employed, during which DE was filtered through an exhaust particle trap. In study IV subjects were exposed to nitrogen dioxide (NO2) at 4 ppm or filtered air.

In study I, thrombus formation and platelet activation were assessed using the Badimon ex vivo perfusion chamber and flow cytometry. Study II comprised the determination of arterial stiffness including pulse wave analysis and velocity.

In studies III-V, vascular assessment was performed using venous occlusion plethysmography. In studies IV and V, the vascular responses to intra-arterially infused endothelial-dependent and endothelial-independent vasodilatators were registered. In study III, vascular responses to intra-arterial infusion of Endothelin-1 (ET-1) and ET-1-receptor antagonists were assessed. Venous occlusion phlethysmography was in all cases performed 4-6 hours following exposures. Blood samples for markers of inflammation, coagulation and platelet activation were collected before and throughout the study periods in studies III and V.

Results: Exposure to DE increased ex vivo thrombus formation and arterial stiffness, in terms of augmentation index. DE inhalation impaired vasomotor function and endogenous fibrinolysis. The exhaust particle trap reduced the particle concentration by 98% and abolished the effects on vasomotor function, endogenous fibrinolysis and ex vivo thrombus formation. Plasma concentrations of ET-1 and its precursor big-ET-1 were unchanged following exposure. Dual endothelial receptor antagonism caused similar vasodilatation after both exposures, although vasodilatation to the endothelin-A receptor alone was blunted after DE exposure. ET-1 infusion induced vasoconstriction only following DE exposure. Exposure to nitrogen dioxide did not affect vascular function.

Conclusion: Inhalation of diesel exhaust in young healthy men impaired important and complementary aspects of vascular function in humans; regulation of vascular tone and endogenous fibrinolysis as well as increased ex vivo thrombus formation. The use of an exhaust particle trap significantly reduced particle emissions and abolished the DE-induced vascular and prothrombotic effects. The adverse vascular effects following DE exposure do not appear to be directly mediated through the endothelin system. Neither is NO2 suggested to be a major arbiter of the DE-induced cardiovascular responses. Arterial stiffness is a non-invasive and easily accessible method and could thus be employed to address vascular function in larger field studies. Taken together, this thesis has given further knowledge about the mechanisms underlying the DE-induced vascular effects.

Place, publisher, year, edition, pages
Umeå: Umeå university , 2009. , 73 p.
Series
Umeå University medical dissertations, ISSN 0346-6612 ; 1317
Keyword [en]
air pollution, diesel exhaust, nitrogen dioxide, endothelin-1, cardiovascular effects, exhaust particle trap
National Category
Respiratory Medicine and Allergy
Research subject
Lung Medicine
Identifiers
URN: urn:nbn:se:umu:diva-27783ISBN: 978-91-7264-868-5 (print)OAI: oai:DiVA.org:umu-27783DiVA: diva2:277668
Public defence
2009-12-11, Sal E04, byggnad 6E, Norrlands Universitetssjukhus, Umeå, 09:00 (English)
Opponent
Supervisors
Available from: 2009-11-23 Created: 2009-11-19 Last updated: 2012-02-22Bibliographically approved
List of papers
1. Diesel exhaust inhalation increases thrombus formation in man
Open this publication in new window or tab >>Diesel exhaust inhalation increases thrombus formation in man
Show others...
2008 (English)In: European Heart Journal, ISSN 0195-668X, E-ISSN 1522-9645, Vol. 29, no 24, 3043-3051 p.Article in journal (Refereed) Published
Abstract [en]

AIMS: Although the mechanism is unclear, exposure to traffic-derived air pollution is a trigger for acute myocardial infarction (MI). The aim of this study is to investigate the effect of diesel exhaust inhalation on platelet activation and thrombus formation in men.

METHODS AND RESULTS: In a double-blind randomized crossover study, 20 healthy volunteers were exposed to dilute diesel exhaust (350 microg/m(3)) and filtered air. Thrombus formation, coagulation, platelet activation, and inflammatory markers were measured at 2 and 6 h following exposure. Thrombus formation was measured using the Badimon ex vivo perfusion chamber. Platelet activation was assessed by flow cytometry. Compared with filtered air, diesel exhaust inhalation increased thrombus formation under low- and high-shear conditions by 24% [change in thrombus area 2229 microm(2), 95% confidence interval (CI) 1143-3315 microm(2), P = 0.0002] and 19% (change in thrombus area 2451 microm(2), 95% CI 1190-3712 microm(2), P = 0.0005), respectively. This increased thrombogenicity was seen at 2 and 6 h, using two different diesel engines and fuels. Diesel exhaust also increased platelet-neutrophil and platelet-monocyte aggregates by 52% (absolute change 6%, 95% CI 2-10%, P = 0.01) and 30% (absolute change 3%, 95% CI 0.2-7%, P = 0.03), respectively, at 2 h following exposure compared with filtered air.

CONCLUSION: Inhalation of diesel exhaust increases ex vivo thrombus formation and causes in vivo platelet activation in man. These findings provide a potential mechanism linking exposure to combustion-derived air pollution with the triggering of acute MI.

Keyword
Air pollution, Particulate matter, Thrombosis, Platelet activation
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-21071 (URN)10.1093/eurheartj/ehn464 (DOI)18952612 (PubMedID)
Available from: 2009-04-02 Created: 2009-04-02 Last updated: 2012-02-22Bibliographically approved
2. Exposure to diesel exhaust increases arterial stiffness in man
Open this publication in new window or tab >>Exposure to diesel exhaust increases arterial stiffness in man
Show others...
2009 (English)In: Particle and Fibre Toxicology, ISSN 1743-8977, E-ISSN 1743-8977, Vol. 6, no 7Article in journal (Refereed) Published
Abstract [en]

Introduction Exposure to air pollution is associated with increased cardiovascular morbidity, although the underlying mechanisms are unclear. Vascular dysfunction reduces arterial compliance and increases central arterial pressure and left ventricular after-load. We determined the effect of diesel exhaust exposure on arterial compliance using a validated non-invasive measure of arterial stiffness.

Methods In a double-blind randomized fashion, 12 healthy volunteers were exposed to diesel exhaust (approximately 350 μg/m3) or filtered air for one hour during moderate exercise. Arterial stiffness was measured using applanation tonometry at the radial artery for pulse wave analysis (PWA), as well as at the femoral and carotid arteries for pulse wave velocity (PWV). PWA was performed 10, 20 and 30 min, and carotid-femoral PWV 40 min, post-exposure. Augmentation pressure (AP), augmentation index (AIx) and time to wave reflection (Tr) were calculated.

Results Blood pressure, AP and AIx were generally low reflecting compliant arteries. In comparison to filtered air, diesel exhaust exposure induced an increase in AP of 2.5 mmHg (p = 0.02) and in AIx of 7.8% (p = 0.01), along with a 16 ms reduction in Tr (p = 0.03), 10 minutes post-exposure.

Conclusion Acute exposure to diesel exhaust is associated with an immediate and transient increase in arterial stiffness. This may, in part, explain the increased risk for cardiovascular disease associated with air pollution exposure. If our findings are confirmed in larger cohorts of susceptible populations, this simple non-invasive method of assessing arterial stiffness may become a useful technique in measuring the impact of real world exposures to combustion derived-air pollution.

National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-27794 (URN)10.1186/1743-8977-6-7 (DOI)
Available from: 2009-11-23 Created: 2009-11-20 Last updated: 2017-12-12Bibliographically approved
3. Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans
Open this publication in new window or tab >>Contribution of endothelin-1 to the vascular effects of diesel exhaust inhalation in humans
Show others...
2009 (English)In: Hypertension, ISSN 0194-911X, E-ISSN 1524-4563, Vol. 54, no 4, 910-915 p.Article in journal (Refereed) Published
Abstract [en]

Diesel exhaust inhalation impairs vascular function, and, althoughthe underlying mechanism remains unclear, endothelin (ET) 1and NO are potential mediators. The aim of this study was toidentify whether diesel exhaust inhalation affects the vascularactions of ET-1 in humans. In a randomized, double-blind crossoverstudy, 13 healthy male volunteers were exposed to either filteredair or dilute diesel exhaust (331±13 µg/m3). Plasmaconcentrations of ET-1 and big-ET-1 were determined at baselineand throughout the 24-hour study period. Bilateral forearm bloodflow was measured 2 hours after the exposure during infusionof either ET-1 (5 pmol/min) or the ETA receptor antagonist,BQ-123 (10 nmol/min) alone and in combination with the ETB receptorantagonist, BQ-788 (1 nmol/min). Diesel exhaust exposure hadno effect on plasma ET-1 and big-ET-1 concentrations (P>0.05for both) or 24-hour mean blood pressure or heart rate (P>0.05for all). ET-1 infusion increased plasma ET-1 concentrationsby 58% (P<0.01) but caused vasoconstriction only after dieselexhaust exposure (–17% versus 2% after air; P<0.001).In contrast, diesel exhaust exposure reduced vasodilatationto isolated BQ-123 infusion (20% versus 59% after air; P<0.001)but had no effect on vasodilatation to combined BQ-123 and BQ-788administration (P>0.05). Diesel exhaust inhalation increasesvascular sensitivity to ET-1 and reduces vasodilatation to ETAreceptor antagonism despite unchanged plasma ET-1 concentrations.Given the tonic interaction between the ET and NO systems, weconclude that diesel exhaust inhalation alters vascular reactivityto ET-1 probably through its effects on NO bioavailability.

Place, publisher, year, edition, pages
Dallas, Tex.: The Association, 2009
Keyword
air pollution, particulate matter, endothelial function, endothelin receptor antagonists, ET-1, endothelin-1, blood pressure
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-27792 (URN)10.1161/HYPERTENSIONAHA.109.135947 (DOI)
Available from: 2009-11-23 Created: 2009-11-20 Last updated: 2017-12-12Bibliographically approved
4. Exposure to nitrogen dioxide is not associated with vascular dysfunction in man
Open this publication in new window or tab >>Exposure to nitrogen dioxide is not associated with vascular dysfunction in man
Show others...
2010 (English)In: Inhalation Toxicology, ISSN 0895-8378, E-ISSN 1091-7691, Vol. 22, no 3, 192-198 p.Article in journal (Refereed) Published
Abstract [en]

Background: Exposure to air pollution is associated with increased cardiorespiratory morbidity and mortality. It is unclear whether these effects are mediated through combustion-derived particulate matter or gaseous components, such as nitrogen dioxide.

Objectives: To investigate the effect of nitrogen dioxide exposure on vascular vasomotor and six fibrinolytic functions.

Methods: Ten healthy male volunteers were exposed to nitrogen dioxide at 4 ppm or filtered air for 1 h during intermittent exercise in a randomized double-blind crossover study. Bilateral forearm blood flow and fibrinolytic markers were measured before and during unilateral intrabrachial infusion of bradykinin (100–1000 pmol/min), acetylcholine (5–20 μg/min), sodium nitroprusside (2–8 μg/min), and verapamil (10–100 μg/min) 4 h after the exposure. Lung function was determined before and after the exposure, and exhaled nitric oxide at baseline and 1 and 4 h after the exposure.

Results: There were no differences in resting forearm blood flow after either exposure. There was a dose-dependent increase in forearm blood flow with all vasodilators but this was similar after either exposure for all vasodilators (p > .05 for all). Bradykinin caused a dose-dependent increase in plasma tissue-plasminogen activator, but again there was no difference between the exposures. There were no changes in lung function or exhaled nitric oxide following either exposure.

Conclusion: Inhalation of nitrogen dioxide does not impair vascular vasomotor or fibrinolytic function. Nitrogen dioxide does not appear to be a major arbiter of the adverse cardiovascular effects of air pollution.

Place, publisher, year, edition, pages
Informa Healthcare, 2010
Keyword
Air pollution, endothelial function, fibrinolysis, nitrogen dioxide, NO2
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-27796 (URN)10.3109/08958370903144105 (DOI)000275067200002 ()
Available from: 2009-11-23 Created: 2009-11-20 Last updated: 2017-12-12Bibliographically approved
5. Exhaust particle traps reduce the adverse vascular and prothrombotic effects associated with diesel exhaust exposure in man
Open this publication in new window or tab >>Exhaust particle traps reduce the adverse vascular and prothrombotic effects associated with diesel exhaust exposure in man
Show others...
(English)Manuscript (preprint) (Other academic)
National Category
Respiratory Medicine and Allergy
Identifiers
urn:nbn:se:umu:diva-27797 (URN)
Available from: 2009-11-23 Created: 2009-11-20 Last updated: 2012-02-22Bibliographically approved

Open Access in DiVA

fulltext(2434 kB)1028 downloads
File information
File name FULLTEXT01.pdfFile size 2434 kBChecksum SHA-512
4003550640c98f1172dd1497d799ff79006a3fc702931d3d58ee5b87d45dc4d0390ef16030b2b5ea833f43a929644336a437d1f1939bf79e58b2fa628dcbd4dc
Type fulltextMimetype application/pdf

Authority records BETA

Lundbäck, Magnus

Search in DiVA

By author/editor
Lundbäck, Magnus
By organisation
Pulmonary Medicine
Respiratory Medicine and Allergy

Search outside of DiVA

GoogleGoogle Scholar
Total: 1028 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 914 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf