Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Not Applicable

Completed

• Conditions: Vascular Function in Healthy Volunteers
• Interventions: Drug: Intravenous infusion of L-NMMA and Nor-epinephrine

• Registration Number: NCT01060930
• Lead Sponsor: University of Edinburgh

Brief Summary

Exposure to combustion-derived fine particulate air pollution is associated with cardiovascular mortality and morbidity. In previous studies, exposure to diesel exhaust (a major constituent of urban particulate air pollution) has been shown to impair two important functions of the vascular endothelium: vascular vasomotor function and endogenous fibrinolysis. Our subsequent studies suggest this impairment of vascular function is mediated by a reduction in nitric oxide bioavailability. In this study we aim to investigate the cardiovascular responses to systemic nitric oxide synthase inhibition following exposure to dilute diesel exhaust.

Detailed Description

Not available

Study Timeline

• Study First Submitted: 2010-01-28
• Study First Submitted QC: 2010-02-01
• Study First Posted: 2010-02-02
• Study Start: 2010-03
• Primary Completion: 2010-06
• Study Completion: 2010-06
• Status Verified: 2011-04
• Last Update Submitted: 2011-12-15
• Last Update Posted: 2011-12-16

Recruitment & Eligibility

• Status: COMPLETED
• Sex: All
• Target Recruitment: 14

Inclusion Criteria

• Healthy volunteers
• Non smokers
• No regular medication (except oral contraceptive)
• No recent respiratory tract infection (within 6 weeks)

Exclusion Criteria

• History of asthma or respiratory disease
• Smoking history
• Pregnancy (positive urinary pregnancy test)

Study & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
Diesel exhaust exposure	Intravenous infusion of L-NMMA and Nor-epinephrine	1 hour exposure to dilute diesel exhaust \~ 300 mcg/m3 - during intermittent exercise
Air exposure	Intravenous infusion of L-NMMA and Nor-epinephrine	1 hour exposure to filtered air during intermittent exercise

Primary Outcome Measures

Name	Time	Method
Blood pressure response to NO inhibition	Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring

Secondary Outcome Measures

Name	Time	Method
Heart rate response to systemic nitric oxide inhibition	Heart rate will be measured continuously throughout the study period using continous electrocardiography
Central arterial stiffness following NO inhibition	Measured at baseline, and every 5 minutes during the 2-hour vascular study
Cardiac output during NO inhibition	Measured at baseline, and every 5 minutes during the 2-hour vascular study
Plasma nitrite (NO) concentrations	Measured at baseline, and every 15 minutes during the 2-hour vascular study
Platelet activation and platelet-monocyte binding	Measured at baseline, and every 30 minutes during the 2-hour vascular study
Heart rate variability	Heart rate will be measured continuously throughout the study period using continous electrocardiography, and HRV subsequently determined for the whole study period and the 2-hour vascular study separately

Trial Locations

Locations (1)

University Hospital Umeå; 🇸🇪 Umeå, Sweden