Does Ultraviolet Irradiation Reduce Platelet Reactivity and Improve Coronary Microvascular Function in Man?

Study Overview
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Brief Summary
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Endothelium derived nitric oxide (NO) regulates vascular tone and blood pressure in man. NO also inhibits platelet aggregation and mediates a variety of beneficial anti-inflammatory and repair mechanisms. NO may also be a mediator in the release of the endogenous fibrinolytic factor, tissue-plasminogen activating factor (t-PA) from the endothelium.1 Via these actions it plays a very important role in protection of the vasculature from atherothrombosis and clinical sequelae such as myocardial infarction and stroke. Visible and ultraviolet (UV) light relax vascular smooth muscles by producing NO in a phenomenon known as photorelaxation.2 The investigators have demonstrated significant stores of pre-formed, bound NO and other nitrosospecies in human skin, which are rapidly released upon exposure to UVA.3 The investigators have demonstrated recently that serum nitrite and nitroso-species are increased after standing in a UVA phototherapy cabinet and that local UVA exposure is associated with increased forearm arterial blood flow that is independent of skin temperature. The investigators have also demonstrated a fall in mean arterial blood pressure in subjects exposed UVA. Cardiovascular morbidity and the prevalence of hypertension vary with latitude. The investigators hypothesise that some of this geographical variation may be explained by a diminished sunlight/UVA exposure with attendant negative effects upon NO bio-availability.4 To further examine the potential beneficial effects of UVA exposure we will examine the effects of whole-body UVA upon platelet activation and upon myocardial/coronary arterial flow reserve. The investigators will correlate these measures with systemic nitrate, nitrite and nitroso-species content in healthy volunteers. HYPOTHESES UVA irradiation enhances coronary flow reserve in healthy volunteers. UVA irradiation suppresses platelet activation in healthy volunteers. UVA irradiation enhances the release of endogenous fibrinolytic factors in healthy volunteers.

Official Title
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Does Ultraviolet Irradiation Reduce Platelet Reactivity and Improve Coronary Microvascular Function in Man?

Conditions
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Hypertension

Intervention / Treatment
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* Radiation: UVA Radiation


Participation Criteria
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Eligibility Criteria
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Inclusion Criteria: Healthy male volunteers aged between 18-45 years (inclusive). Exclusion Criteria: Inability to provide informed consent Co-existent systemic disease (including any history of asthma, reactive airways disease or hypertension) Contraindication to UVA treatment Any history of cardiac conduction abnormality (including bundle branch block or atrial fibrillation) Smoker Current intake of aspirin, other non-steroid anti-inflammatory medications or any regular medication. Recent infective/inflammatory condition Echocardiographic evidence of left ventricular hypertrophy (left ventricular septal diameter >1.2 cm in diastole), systolic dysfunction or significant valvular stenosis or regurgitation.

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 45 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Design Details

Primary Purpose: Basic Science
Allocation: Randomized
Intervention Model: Crossover Assignment
Masking: None (Open Label)


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Sham Comparator: Sham UVA<br>sham exposure will be provided by covering the UVA lamps with space blanket. | Radiation: UVA Radiation<br>* UVA radiation exposure for 20 minutes<br>|
| Experimental: UVA Radiation<br>Patients will be exposed to UVA radiation for 20 minutes | Radiation: UVA Radiation<br>* UVA radiation exposure for 20 minutes<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Coronary Flow Reserve | Change in coronary flow assessed pre and post UVA radiation versus control | 0, 20, 40 and 60 mins | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Platelet Activation | Platelet activation assessed using platelet monocyte activity | 0, 20, 40 and 60 mins | 
| Endogenous Fibrinolysis | Assessed using flow cytometry | 0, 20, 40 and 60 minutes | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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hypertension, UV radiation, coronary flow reserve, nitric oxide