Combustion Derived Air Pollution and Vascular Function

Official Title: “The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)”

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.

Intervention(s) in this Clinical Trial

• Procedure: Forearm 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).
• Procedure: Badimon Chamber
  • Ex-vivo assessment of thrombus formation using Badimon Chamber

Arms, Groups and Cohorts in this Clinical Trial

• Experimental: Filtered Air Exposure
  • 1 hour exposure to filtered air during intermittent exercise
• Experimental: Diesel Exhaust Exposure
  • 1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
• Experimental: Filtered Diesel Exposure
  • 1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
• Experimental: PALAS Exposure
  • 1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise

Primary Measures

• Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
  • Time Frame: 6-8 hours after exposure
    Safety Issue?: No

Secondary Measures

• Ex-vivo thrombus formation assessed using the Badimon chamber
  • Time Frame: 6 hours after exposure
    Safety Issue?: No
• Arterial stiffness measured by radial artery tonometry
  • Time Frame: Before and after exposure
    Safety Issue?: No
• Heart rate and heart rate variability measured with 3 lead Holter electrographic monitors
  • Time Frame: During and for 24 hours after exposure
    Safety Issue?: No
• Blood pressure
  • Time Frame: During and after exposure and during forearm study
    Safety Issue?: No
• Plasma t-PA and PAI concentrations following infusion of bradykinin
  • Time Frame: During forearm study
    Safety Issue?: No
• Plasma inflammatory markers IL-6, TNF-alpha, IL-1 and hsCRP
  • Time Frame: Before and after exposure
    Safety Issue?: No
• Platelet monocyte binding as measured by flow cytometry
  • Time Frame: After the exposure
    Safety Issue?: No

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

Gender Eligibility for this Clinical Trial: Both

Minimum Age for this Clinical Trial: N/A

Maximum Age for this Clinical Trial: N/A

Are Healthy Volunteers Accepted for this Clinical Trial?: Accepts Healthy Volunteers

Lead Investigator: University of Edinburgh Other

Overall Clinical Trial Officials and Contacts

Nicholas L Mills, MB BCh MRCP Principal Investigator University of Edinburgh  

Information obtained from ClinicalTrials.gov on February 12, 2012

Link to the current ClinicalTrials.gov record. http://clinicaltrials.gov/show/NCT00775099

Study ID Number: 05/S1103/46

ClinicalTrials.gov Identifier: NCT00775099

Health Authority: United Kingdom: Research Ethics Committee