Clinical trial NCT01060930: Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output
Official title: Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Vascular Function in Healthy Volunteers
Keywords: Nitric oxide
Diesel exhaust
Air pollution
Cardiac output
Healthy volunteers
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: NHS Lothian
name: Umeå University
First posted: 2010-02-02
Enrollment: 14
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

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.


Eligibility criteria: 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)

Primary outcomes:
measure: Blood pressure response to NO inhibition
timeFrame: Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring
Secondary outcomes:
measure: Heart rate response to systemic nitric oxide inhibition
timeFrame: Heart rate will be measured continuously throughout the study period using continous electrocardiography
measure: Central arterial stiffness following NO inhibition
timeFrame: Measured at baseline, and every 5 minutes during the 2-hour vascular study
measure: Cardiac output during NO inhibition
timeFrame: Measured at baseline, and every 5 minutes during the 2-hour vascular study
measure: Plasma nitrite (NO) concentrations
timeFrame: Measured at baseline, and every 15 minutes during the 2-hour vascular study
measure: Platelet activation and platelet-monocyte binding
timeFrame: Measured at baseline, and every 30 minutes during the 2-hour vascular study
measure: Heart rate variability
timeFrame: 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
Other outcomes:
Locations:
city: Umeå
country: Sweden
facility: University Hospital Umeå
Study officials:
affiliation: University of Edinburgh
name: Jeremy P Langrish, MB BCh MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: Langrish JP, Unosson J, Bosson J, Barath S, Muala A, Blackwell S, Soderberg S, Pourazar J, Megson IL, Treweeke A, Sandstrom T, Newby DE, Blomberg A, Mills NL. Altered nitric oxide bioavailability contributes to diesel exhaust inhalation-induced cardiovascular dysfunction in man. J Am Heart Assoc. 2013 Feb 19;2(1):e004309. doi: 10.1161/JAHA.112.004309.