The Effects of Combustion-Derived Air Pollution on Vascular Vasomotor and Fibrinolytic Function in Healthy Volunteers (Diesel Exposure)
试验速览
- 阶段
- 不适用
- 状态
- 已完成
- 入组人数
- 16
- 试验地点
- 1
- 主要终点
- Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
研究概览
简要总结
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:
- Combustion derived nanoparticulate causes an acute impairment of endothelial vasomotor and fibrinolytic function in healthy volunteers.
- Exposure to combustion derived air pollution is associated with increased thrombus formation.
研究设计
- 研究类型
- Interventional
- 分配方式
- Randomized
- 干预模型
- Crossover
- 主要目的
- Basic Science
- 盲法
- Triple (Participant, Investigator, Outcomes Assessor)
入排标准
- 性别
- All
- 接受健康志愿者
- 是
入选标准
- •Healthy volunteers
排除标准
- •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
研究组 & 干预措施
Filtered Air Exposure
1 hour exposure to filtered air during intermittent exercise
干预措施: Forearm Vascular Study (Procedure)
Filtered Air Exposure
1 hour exposure to filtered air during intermittent exercise
干预措施: Badimon Chamber (Procedure)
Diesel Exhaust Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
干预措施: Forearm Vascular Study (Procedure)
Diesel Exhaust Exposure
1 hour exposure to dilute diesel exhaust at a concentration of 300 µg/m3 during intermittent exercise
干预措施: Badimon Chamber (Procedure)
Filtered Diesel Exposure
1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
干预措施: Forearm Vascular Study (Procedure)
Filtered Diesel Exposure
1 hour exposure to diesel exhaust with all particulates filtered out using teflon filter with intermittent exercise
干预措施: Badimon Chamber (Procedure)
PALAS Exposure
1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise
干预措施: Forearm Vascular Study (Procedure)
PALAS Exposure
1 hour exposure to pure carbon particles produced by PALAS generator during intermittent exercise
干预措施: Badimon Chamber (Procedure)
结局指标
主要结局
Forearm blood flow measured by forearm venous occlusion plethysmography in response to infused vasodilators
时间窗: 6-8 hours after exposure
次要结局
- 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)
- Blood pressure(During and after exposure and during forearm study)
- 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)