European Heart Journal Advance Access originally published online on October 24, 2008
European Heart Journal 2008 29(24):3043-3051; doi:10.1093/eurheartj/ehn464
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Diesel exhaust inhalation increases thrombus formation in man
1 Centre for Cardiovascular Science, University of Edinburgh, Edinburgh, UK
2 Department of Respiratory Medicine and Allergy, Umeå University, Umeå, Sweden
3 National Institute for Public Health and Environment (RIVM), The Netherlands
4 Mount Sinai, New York, USA
Received 28 February 2008; revised 18 September 2008; accepted 29 September 2008; online publish-ahead-of-print 24 October 2008.
* Corresponding author. Department of Cardiovascular Sciences, University of Edinburgh, Room SU 305, Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SU, UK. Tel: +44 131 242 6429, Fax: +44 131 242 6379, Email: andrew.lucking{at}btinternet.com
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 µg/m3) 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 µm2, 95% confidence interval (CI) 1143–3315 µm2, P = 0.0002] and 19% (change in thrombus area 2451 µm2, 95% CI 1190–3712 µm2, 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.
Key Words: Air pollution Particulate matter Thrombosis Platelet activation
Studies performed at The Centre for Cardiovascular Science, University of Edinburgh, UK and at the Department of Respiratory Medicine and Allergy, Umeå University, Sweden