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

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

1. UVA irradiation enhances coronary flow reserve in healthy volunteers.
2. UVA irradiation suppresses platelet activation in healthy volunteers.
3. UVA irradiation enhances the release of endogenous fibrinolytic factors in healthy volunteers.

Study Overview

• Status: Completed
• Conditions: Hypertension
• Intervention / Treatment: Radiation: UVA Radiation

• Study Type: Interventional
• Enrollment (Actual): 12
• Phase: Not Applicable

Contacts and Locations

Study Locations

• United Kingdom
  • Lothian
    • Edinburgh, Lothian, United Kingdom, Eh16 4SA
      • University of Edinburgh

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 45 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: Male

Description

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.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: NONE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
SHAM_COMPARATOR: Sham UVA; sham exposure will be provided by covering the UVA lamps with space blanket.	Radiation: UVA Radiation; UVA radiation exposure for 20 minutes
EXPERIMENTAL: UVA Radiation; Patients will be exposed to UVA radiation for 20 minutes	Radiation: UVA Radiation; UVA radiation exposure for 20 minutes

What is the study measuring?

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

Collaborators and Investigators

• Sponsor: University of Edinburgh
• Investigators: Principal Investigator: Ninian Lang, MbChB, University of Edinburgh

Study record dates

Study Major Dates

• Study Start: March 1, 2012
• Primary Completion (ACTUAL): August 1, 2012
• Study Completion (ACTUAL): August 1, 2012

Study Registration Dates

• First Submitted: June 20, 2012
• First Submitted That Met QC Criteria: February 4, 2013
• First Posted (ESTIMATE): February 7, 2013

Study Record Updates

• Last Update Posted (ESTIMATE): February 20, 2013
• Last Update Submitted That Met QC Criteria: February 19, 2013
• Last Verified: February 1, 2013

More Information

Terms related to this study

• Keywords: hypertension; coronary flow reserve; nitric oxide; UV radiation
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Vascular Diseases; Hypertension
• Other Study ID Numbers: UVA Study