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

This study has been completed.
Sponsor:
Collaborators:
NHS Lothian
Umeå University
Information provided by (Responsible Party):
University of Edinburgh
ClinicalTrials.gov Identifier:
NCT01060930
First received: January 28, 2010
Last updated: December 15, 2011
Last verified: April 2011
  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: Double Blind (Subject, 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 ] [ Designated as safety issue: No ]

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 ] [ Designated as safety issue: No ]
  • Central arterial stiffness following NO inhibition [ Time Frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study ] [ Designated as safety issue: No ]
  • Cardiac output during NO inhibition [ Time Frame: Measured at baseline, and every 5 minutes during the 2-hour vascular study ] [ Designated as safety issue: No ]
  • Plasma nitrite (NO) concentrations [ Time Frame: Measured at baseline, and every 15 minutes during the 2-hour vascular study ] [ Designated as safety issue: No ]
  • Platelet activation and platelet-monocyte binding [ Time Frame: Measured at baseline, and every 30 minutes during the 2-hour vascular study ] [ Designated as safety issue: No ]
  • 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 ] [ Designated as safety issue: No ]

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

Ages Eligible for Study:   18 Years and older
Genders Eligible for Study:   Both
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
Choosing to participate in a study is an important personal decision. Talk with your doctor and family members or friends about deciding to join a study. To learn more about this study, you or your doctor may contact the study research staff using the Contacts provided below. For general information, see Learn About Clinical Studies.

Please refer to this study by its ClinicalTrials.gov identifier: 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

No publications provided by University of Edinburgh

Additional 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
Study First Received: January 28, 2010
Last Updated: December 15, 2011
Health Authority: Sweden: Regional Ethical Review Board

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

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

ClinicalTrials.gov processed this record on July 23, 2014