Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

NCT01060930 | Completed

• 1 other identifier: DISCO
• Study Type: interventional
• Target: 14
• Locations: 1 country
• Sites: 1

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.

Conditions

Vascular Function in Healthy Volunteers

Keywords

Nitric oxide; Diesel exhaust; Air pollution; Cardiac output; Healthy volunteers

Outcome Measures

Primary Outcomes (1)

• Blood pressure response to NO inhibition

  Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring

Secondary Outcomes (6)

• 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

Study Arms (2)

Diesel exhaust exposure

EXPERIMENTAL

1 hour exposure to dilute diesel exhaust \~ 300 mcg/m3 - during intermittent exercise

Drug: Intravenous infusion of L-NMMA and Nor-epinephrine

Air exposure

EXPERIMENTAL

1 hour exposure to filtered air during intermittent exercise

Drug: Intravenous infusion of L-NMMA and Nor-epinephrine

Interventions

Intravenous infusion of L-NMMA and Nor-epinephrine DRUG

Intravenous infusion of 3mg/kg L-NMMA (L-NG-monomethyl arginine; NO synthase inhibitor) and nor-epinephrine at 50 ng/kg/min. Each infusion to run over 15 mins and separated by 45 min to allow return to baseline. Drugs infused in a randomised order. During the study, blood pressure will be measured invasively using an intra-arterial radial artery cannula, central arterial stiffness measured using peripheral arterial tonometry and cardiac output using thoracic bioimpedance.

Also known as: L-NMMA: Clinalfa Basic, Bachem, Germany

Air exposure; Diesel exhaust exposure

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

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

Sponsors & Collaborators

• University of Edinburgh: lead
• NHS Lothian: collaborator
• Umeå University: collaborator

Study Sites (1)

University Hospital Umeå

Umeå, Sweden

Location

Related Publications (1)

• 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.

  PMID: 23525434 DERIVED

Study Officials

• Jeremy P Langrish, MB BCh MRCP

  University of Edinburgh

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: TRIPLE
• Who Masked: PARTICIPANT, INVESTIGATOR, OUTCOMES ASSESSOR
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: January 28, 2010
• First Posted: February 2, 2010
• Study Start: March 1, 2010
• Primary Completion: June 1, 2010
• Study Completion: June 1, 2010
• Last Updated: December 16, 2011

Record last verified: 2011-04

Locations

SE (1)