doi: 10.1161/CIRCULATIONAHA.105.588962
(Circulation. 2005;112:3930-3936.)
© 2005 American Heart Association, Inc.
Vascular Medicine |
Diesel Exhaust Inhalation Causes Vascular Dysfunction and Impaired Endogenous Fibrinolysis
From the Centre for Cardiovascular Science (N.L.M., S.D.R., N.A.B., D.E.N.), Edinburgh University, Edinburgh, Scotland; the Department of Respiratory Medicine and Allergy (H.T., M.G., A.B., T.S.), Umeå University, Umeå, Sweden; and the Wellcome Trust Clinical Research Facility (K. Darnley) and ELEGI Colt Laboratory (W.M., K. Donaldson), Centre for Inflammation Research, Edinburgh University, Edinburgh, Scotland.
Reprint requests to Dr Nicholas L. Mills, Centre for Cardiovascular Science, University of Edinburgh, Chancellor’s Bldg, Edinburgh, EH16 4SU, UK. E-mail nick.mills{at}ed.ac.uk
Received December 14, 2004; de novo received August 12, 2005; revision received September 14, 2005; accepted October 7, 2005.
Background— Although the mechanisms are unknown, it has been suggested that transient exposure to traffic-derived air pollution may be a trigger for acute myocardial infarction. The study aim was to investigate the effects of diesel exhaust inhalation on vascular and endothelial function in humans.
Methods and Results— In a double-blind, randomized, cross-over study, 30 healthy men were exposed to diluted diesel exhaust (300 µg/m3 particulate concentration) or air for 1 hour during intermittent exercise. Bilateral forearm blood flow and inflammatory factors were measured before and during unilateral intrabrachial bradykinin (100 to 1000 pmol/min), acetylcholine (5 to 20 µg/min), sodium nitroprusside (2 to 8 µg/min), and verapamil (10 to 100 µg/min) infusions 2 and 6 hours after exposure. There were no differences in resting forearm blood flow or inflammatory markers after exposure to diesel exhaust or air. Although there was a dose-dependent increase in blood flow with each vasodilator (P<0.0001 for all), this response was attenuated with bradykinin (P<0.05), acetylcholine (P<0.05), and sodium nitroprusside (P<0.001) infusions 2 hours after exposure to diesel exhaust, which persisted at 6 hours. Bradykinin caused a dose-dependent increase in plasma tissue plasminogen activator (P<0.0001) that was suppressed 6 hours after exposure to diesel (P<0.001; area under the curve decreased by 34%).
Conclusions— At levels encountered in an urban environment, inhalation of dilute diesel exhaust impairs 2 important and complementary aspects of vascular function in humans: the regulation of vascular tone and endogenous fibrinolysis. These important findings provide a potential mechanism that links air pollution to the pathogenesis of atherothrombosis and acute myocardial infarction.
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