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.
Study Type
INTERVENTIONAL
Allocation
RANDOMIZED
Purpose
BASIC_SCIENCE
Masking
TRIPLE
Enrollment
16
Forearm venous occlusion plethysmography to measure forearm blood flow during intra-arterial infusion of the vasodilators Verapamil (10-100 µg/min), bradykinin (100-1000 pmol/min), sodium nitroprusside (2-8 µg/min) and Acetylcholine (5-20 mg/min).
Ex-vivo assessment of thrombus formation using Badimon Chamber
University of Edinburgh
Edinburgh, United Kingdom
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
Time frame: 6-8 hours after exposure
Ex-vivo thrombus formation assessed using the Badimon chamber
Time frame: 6 hours after exposure
Arterial stiffness measured by radial artery tonometry
Time frame: Before and after exposure
Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
Time frame: During and for 24 hours after exposure
Blood pressure
Time frame: During and after exposure and during forearm study
Plasma t-PA and PAI concentrations following infusion of bradykinin
Time frame: During forearm study
Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
Time frame: Before and after exposure
Platelet monocyte binding as measured by flow cytometry
Time frame: After the exposure
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