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| Name | Class |
|---|---|
| NHS Lothian | OTHER_GOV |
| Umeå University | OTHER |
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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.
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| Label | Type | Description | Intervention Names |
|---|---|---|---|
| Diesel exhaust exposure | Experimental | 1 hour exposure to dilute diesel exhaust ~ 300 mcg/m3 - during intermittent exercise |
|
| Air exposure | Experimental | 1 hour exposure to filtered air during intermittent exercise |
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| Name | Type | Description | Arm Group Labels | Other Names |
|---|---|---|---|---|
| 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. |
| Measure | Description | Time Frame |
|---|---|---|
| Blood pressure response to NO inhibition | Blood pressure will be measured continuously through the vascular study using intra-arterial monitoring |
| Measure | Description | Time Frame |
|---|---|---|
| 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 |
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Inclusion Criteria:
Exclusion Criteria:
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| Name | Affiliation | Role |
|---|---|---|
| Jeremy P Langrish, MB BCh MRCP | University of Edinburgh | Principal Investigator |
| Facility | Status | City | State | ZIP | Country | Contacts |
|---|---|---|---|---|---|---|
| University Hospital Umeå | Umeå | Sweden |
| PubMed Identifier | Type | Citation | Retractions |
|---|---|---|---|
| 23525434 | Derived | 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. |
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| 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 |
| Heart rate variability | 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 |