The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

Coronary Disease Clinical Trial

Official title:

The Effects of Diesel Exhaust Inhalation on Vascular Function - the Role of Endothelin

Clinical Trial Details — Status: Completed

Administrative data

• NCT number: NCT00745693
• Other study ID #: Res08/A116
• Status: Completed
• Phase: N/A
• Start date: March 2008
• Est. completion date: May 2008

Study information

• Verified date: September 2008
• Source: University of Edinburgh
• Contact: n/a
• Is FDA regulated: No
• Study type: Interventional

Clinical Trial Summary

The purpose of this study is to identify the role of endothelin 1 (a natural vasoconstrictor) in the adverse vascular effects demonstrated after exposure to air pollution

Description:

Air pollution is a major problem, and can be linked to around 5% of all deaths worldwide each year. There are strong associations between air pollution exposure and heart disease but we do not yet understand how these harmful effects are mediated. Understanding this mechanism is likely to have a major impact on the way we treat patients with heart disease and have the potential to shape future environmental health policy. The upregulation of Endothelin-1 provides a plausible mechanism for these harmful effects, and we plan to investigate this in more depth in the human forearm following exposure to diesel exhaust.

Recruitment information / eligibility

• Status: Completed
• Enrollment: 15
• Est. completion date: May 2008
• Est. primary completion date: May 2008
• Accepts healthy volunteers: Accepts Healthy Volunteers
• Gender: Male
• Age group: 18 Years to 35 Years

Eligibility

Inclusion Criteria:

• Healthy male volunteers

Exclusion Criteria:

• Use of regular medication

• Cigarette smoking

• Significant occupational exposure to air pollution

• Intercurrent illness

Related Conditions & MeSH terms

• Coronary Disease

Intervention

Drug:
• Endothelin-1
Intra-arterial infusion of Endothelin-1 at 5pmol/min for 1 hour during venous occlusion plethysmography
• BQ-123 and BQ-788
1 hour intra-arterial infusion of BQ-123 at 10nmol/min followed by co-infusion of BQ-788 at 1nmol/min for a further hour during forearm venous occlusion plethysmography

Locations

Country	Name	City	State
Sweden	Umeå University	Umeå	Västerbottens

Sponsors (2)

Lead Sponsor	Collaborator
University of Edinburgh	Umeå University

Country where clinical trial is conducted

Sweden, 

References & Publications (5)

Calderon-Garciduenas L, Vincent R, Mora-Tiscareno A, Franco-Lira M, Henriquez-Roldan C, Barragan-Mejia G, Garrido-Garcia L, Camacho-Reyes L, Valencia-Salazar G, Paredes R, Romero L, Osnaya H, Villarreal-Calderon R, Torres-Jardon R, Hazucha MJ, Reed W. Elevated plasma endothelin-1 and pulmonary arterial pressure in children exposed to air pollution. Environ Health Perspect. 2007 Aug;115(8):1248-53. doi: 10.1289/ehp.9641. — View Citation

Mills NL, Tornqvist 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. doi: 10.1161/CIRCULATIONAHA.105.588962. — View Citation

Peretz A, Sullivan JH, Leotta DF, Trenga CA, Sands FN, Allen J, Carlsten C, Wilkinson CW, Gill EA, Kaufman JD. Diesel exhaust inhalation elicits acute vasoconstriction in vivo. Environ Health Perspect. 2008 Jul;116(7):937-42. doi: 10.1289/ehp.11027. — View Citation

Tornqvist H, Mills NL, Gonzalez M, Miller MR, Robinson SD, Megson IL, Macnee W, Donaldson K, Soderberg S, Newby DE, Sandstrom T, Blomberg A. Persistent endothelial dysfunction in humans after diesel exhaust inhalation. Am J Respir Crit Care Med. 2007 Aug 15;176(4):395-400. doi: 10.1164/rccm.200606-872OC. Epub 2007 Apr 19. — View Citation

Vincent R, Kumarathasan P, Goegan P, Bjarnason SG, Guenette J, Berube D, Adamson IY, Desjardins S, Burnett RT, Miller FJ, Battistini B. Inhalation toxicology of urban ambient particulate matter: acute cardiovascular effects in rats. Res Rep Health Eff Inst. 2001 Oct;(104):5-54; discussion 55-62. — View Citation

Outcome

Type	Measure	Description	Time frame	Safety issue
Primary	Change in forearm blood flow following infusion of endothelin-1 or the endothelin receptor antagonists BQ-123 & BQ-788		2 hours after exposure
Secondary	24 hour mean blood pressure (ambulatory monitoring)		24 hours following the exposure
Secondary	Systemic endothelin-1 and big endothelin-1 concentrations		At baseline, and immediately, 1, 2, 3, 4, 6 and 24 hours after exposure
Secondary	Changes in arterial stiffness (pulse-wave velocity)		During and for the 1 hour after the exposure