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Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output (DISCO)

This study has been completed.
Sponsor:
ClinicalTrials.gov Identifier:
NCT01060930
First Posted: February 2, 2010
Last Update Posted: December 16, 2011
The safety and scientific validity of this study is the responsibility of the study sponsor and investigators. Listing a study does not mean it has been evaluated by the U.S. Federal Government. Read our disclaimer for details.
Collaborators:
NHS Lothian
Umeå University
Information provided by (Responsible Party):
University of Edinburgh
  Purpose
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.

Condition Intervention
Vascular Function in Healthy Volunteers Drug: Intravenous infusion of L-NMMA and Nor-epinephrine

Study Type: Interventional
Study Design: Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: Triple (Participant, Investigator, Outcomes Assessor)
Primary Purpose: Basic Science
Official Title: Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

Resource links provided by NLM:


Further study details as provided by University of Edinburgh:

Primary Outcome Measures:
  • Blood pressure response to NO inhibition [ Time Frame: Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring ]

Secondary Outcome Measures:
  • Heart rate response to systemic nitric oxide inhibition [ Time Frame: Heart rate will be measured continuously throughout the study period using continous electrocardiography ]
  • Central arterial stiffness following NO inhibition [ Time Frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study ]
  • Cardiac output during NO inhibition [ Time Frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study ]
  • Plasma nitrite (NO) concentrations [ Time Frame: Measured at baseline, and every 15 minutes during the 2-hour vascular study ]
  • Platelet activation and platelet-monocyte binding [ Time Frame: Measured at baseline, and every 30 minutes during the 2-hour vascular study ]
  • Heart rate variability [ Time Frame: 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 ]

Enrollment: 14
Study Start Date: March 2010
Study Completion Date: June 2010
Primary Completion Date: June 2010 (Final data collection date for primary outcome measure)
Arms Assigned Interventions
Experimental: Diesel exhaust exposure
1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise
Drug: Intravenous infusion of L-NMMA and Nor-epinephrine
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.
Other Name: L-NMMA: Clinalfa Basic, Bachem, Germany
Experimental: Air exposure
1 hour exposure to filtered air during intermittent exercise
Drug: Intravenous infusion of L-NMMA and Nor-epinephrine
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.
Other Name: L-NMMA: Clinalfa Basic, Bachem, Germany

  Eligibility

Information from the National Library of Medicine

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Ages Eligible for Study:   18 Years and older   (Adult, Senior)
Sexes Eligible for Study:   All
Accepts Healthy Volunteers:   Yes
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)
  Contacts and Locations
Information from the National Library of Medicine

To learn more about this study, you or your doctor may contact the study research staff using the contact information provided by the sponsor.

Please refer to this study by its ClinicalTrials.gov identifier (NCT number): NCT01060930


Locations
Sweden
University Hospital Umeå
Umeå, Sweden
Sponsors and Collaborators
University of Edinburgh
NHS Lothian
Umeå University
Investigators
Principal Investigator: Jeremy P Langrish, MB BCh MRCP University of Edinburgh
  More Information

Publications automatically indexed to this study by ClinicalTrials.gov Identifier (NCT Number):
Responsible Party: University of Edinburgh
ClinicalTrials.gov Identifier: NCT01060930     History of Changes
Other Study ID Numbers: DISCO
First Submitted: January 28, 2010
First Posted: February 2, 2010
Last Update Posted: December 16, 2011
Last Verified: April 2011

Keywords provided by University of Edinburgh:
Nitric oxide
Diesel exhaust
Air pollution
Cardiac output
Healthy volunteers

Additional relevant MeSH terms:
Epinephrine
Racepinephrine
Norepinephrine
Nitric Oxide
Epinephryl borate
omega-N-Methylarginine
Adrenergic alpha-Agonists
Adrenergic Agonists
Adrenergic Agents
Neurotransmitter Agents
Molecular Mechanisms of Pharmacological Action
Physiological Effects of Drugs
Adrenergic beta-Agonists
Bronchodilator Agents
Autonomic Agents
Peripheral Nervous System Agents
Anti-Asthmatic Agents
Respiratory System Agents
Mydriatics
Sympathomimetics
Vasoconstrictor Agents
Free Radical Scavengers
Antioxidants
Endothelium-Dependent Relaxing Factors
Vasodilator Agents
Gasotransmitters
Protective Agents
Enzyme Inhibitors