Endothelial Dysfunction
Conditions
Keywords
Air Pollution, Particles, Particulate Matter, Vascular function, Endothelial function, Thrombosis
Brief summary
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.
Interventions
PROCEDUREForearm Vascular Study
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).
PROCEDUREBadimon Chamber
Ex-vivo assessment of thrombus formation using Badimon Chamber
Sponsors
National Institute for Public Health and the Environment (RIVM)
University of Edinburgh
Study design
Allocation
RANDOMIZED
Intervention model
CROSSOVER
Primary purpose
BASIC_SCIENCE
Masking
TRIPLE (Subject, Investigator, Outcomes Assessor)
Eligibility
Sex/Gender
ALL
Healthy volunteers
Yes
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
Design outcomes
Primary
| Measure | Time frame |
|---|---|
| Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators | 6-8 hours after exposure |
Secondary
| Measure | Time frame |
|---|---|
| Ex-vivo thrombus formation assessed using the Badimon chamber | 6 hours after exposure |
| Arterial stiffness measured by radial artery tonometry | Before and after exposure |
| Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors | During and for 24 hours after exposure |
| Plasma t-PA and PAI concentrations following infusion of bradykinin | During forearm study |
| Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP | Before and after exposure |
| Platelet monocyte binding as measured by flow cytometry | After the exposure |
| Blood pressure | During and after exposure and during forearm study |
Countries
United Kingdom
Outcome results
None listed