Air pollution is a major cause of cardiovascular morbidity and mortality. The components of air pollution responsible and the mechanisms through which they might mediate these harmful effects remain only partially understood. The link between cardiovascular disease and air pollution is strongest for fine particulate matter. Fine particulate matter (PM) is produced from the combustion of fossil fuels with the most significant threat thought to be posed by small particles less than 10µm (PM 10) which can be inhaled into the lungs. We propose to identify the precise component of diesel exhaust that mediates the adverse cardiovascular effects using a carbon particle generator, and a particle concentrator. The aim of this study proposal is to assess the vascular effects of different types and components of air pollution in healthy subjects. We intend to test the hypotheses that:

1. Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
2. Exposure to combustion derived air pollution is associated with increased thrombus formation.

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Current smokers
• Significant occupational exposure to air pollution
• History of lung disease
• Women of child-bearing potential
• Malignant arrhythmias
• Renal or hepatic failure
• Significant co-morbidity
• Systolic blood pressure >190 or <100 mmHg
• Previous history of blood dyscrasia
• Unable to tolerate the supine position
• Lack of informed consent
• Blood donation within last 3 months