The Cardiovascular Effects of Air Pollution: the Role of Nitric Oxide

Endothelial Dysfunction Clinical Trial

Official title:

The Cardiovascular Effects of Air Pollution: the Role of Nitric Oxide

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00845767
• Other study ID #: DNR 08-185M/1
• Status: Completed
• Phase: N/A
• First received: February 17, 2009
• Last updated: October 8, 2009
• Start date: April 2009
• Est. completion date: July 2009

Study information

• Verified date: October 2009
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Health authority: Sweden: Regional Ethical Review Board
• Study type: Interventional

Clinical Trial Summary

Exposure to air pollution has been linked to increased cardiorespiratory morbidity and mortality. The exact component of air pollution that mediates this effect is unknown, but the link is strongest for fine combustion derived particulate matter derived from traffic sources. Recently, it has been demonstrated that inhalation of diesel exhaust impairs vascular vasomotor tone and endogenous fibrinolysis. The mechanism underlying these detrimental vascular is unclear, but is thought to be via oxidative stress and altered bioavailability of endogenous nitric oxide. In these studies we plan to elucidate the role of endogenous nitric oxide (NO) in the adverse vascular responses observed following exposure to diesel exhaust.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 16
• Est. completion date: July 2009
• Est. primary completion date: July 2009
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Both
• Age group: 18 Years to 40 Years

Eligibility

Inclusion Criteria:

• Healthy volunteers

Exclusion Criteria:

• Use of regular medication (except oral contraceptive pill)

• Current smokers

• Significant occupational exposure to air pollution

• Intercurrent illness

Study Design

Allocation: Randomized, Intervention Model: Crossover Assignment, Masking: Double Blind (Subject, Investigator, Outcomes Assessor), Primary Purpose: Basic Science

Related Conditions & MeSH terms

• Endothelial Dysfunction

Intervention

Procedure:
• Forearm Vascular Study
Forearm venous occlusion plethysmography during intraarterial infusion of L-NMMA (2-8 µmol/min) followed by co-infusion of sodium nitroprusside (90-900 ng/min) as a "nitric oxide clamp". Forearm blood flow then measured during the clamp in response to infused vasodilators acetylcholine (5-20 mg/min), bradykinin (100-1000 pmol/min), verapamil (10-100 µg/min) and sodium nitroprusside (2-8 µg/min).

Locations

Country	Name	City	State
Sweden	Umeå University	Umeå

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	Umeå University

Country where clinical trial is conducted

Sweden, 

References & Publications (1)

Mills NL, Törnqvist H, Robinson SD, Gonzalez M, Darnley K, MacNee W, Boon NA, Donaldson K, Blomberg A, Sandstrom T, Newby DE. Diesel exhaust inhalation causes vascular dysfunction and impaired endogenous fibrinolysis. Circulation. 2005 Dec 20;112(25):3930-6. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Forearm blood flow as measured by venous occlusion plethysmography during infusion of NOS inhibitors and vasodilators		2-4 hours after exposure	No
Secondary	Plasma nitrite concentrations		During forearm study	No
Secondary	Plasma concentrations of t-PA and PAI		After infusion of bradykinin during forearm study	No