Diesel Exhaust Inhalation, Systemic Nitric Oxide Inhibition and Cardiac Output

University of Edinburgh14 enrolled

Overview

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.

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

TRIPLE

Enrollment

Conditions

Vascular Function in Healthy Volunteers

Interventions

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.

Eligibility

Sex: ALLMin age: 18 YearsHealthy volunteers:

Medical Language ↔ Plain English

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)

Outcomes

Primary Outcomes

Blood pressure response to NO inhibition

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

Secondary Outcomes

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