Myocardial Ischaemia After Exposure to Diesel Exhaust

University of Edinburgh28 enrolled

Overview

Exposure to particulate air pollution is associated with increases in cardiovascular mortality and morbidity. The pathophysiological mechanisms underlying this observation are emerging, and exposure to particulate air pollution has been shown to result in increases in blood pressure and arterial tone, impaired vascular function and an increased tendency for blood to clot as well as an increase in atherosclerotic plaque burden. Recent evidence from panel studies and controlled exposure studies have suggested an increase in myocardial ischaemia (a reduction in blood flow to the heart) following exposure. In this study we aim to investigate directly myocardial (heart) blood flow following exposure to diesel exhaust (as a model of urban air pollution) using CT/PET myocardial perfusion imaging in male patients with stable coronary disease and healthy male controls. We hypothesize that following exposure to dilute diesel exhaust: 1. Myocardial blood flow will be reduced 2. Coronary flow reserve will be impaired 3. The magnitude of impairment will be higher in patients with coronary disease as compared to healthy controls

Study Type

INTERVENTIONAL

Allocation

RANDOMIZED

Purpose

BASIC_SCIENCE

Masking

QUADRUPLE

Enrollment

Conditions

Coronary Heart Disease

Interventions

Eligibility

Sex: MALEMin age: 18 YearsMax age: 60 YearsHealthy volunteers:

Medical Language ↔ Plain English

Inclusion Criteria: * Healthy volunteers will be taking no regular medication, have a normal electrocardiogram and exercise stress test * Patients with a previous history of myocardial infarction or successful coronary revascularization (PTCA or coronary artery bypass grafting) but without symptoms of angina pectoris will be recruited Exclusion Criteria: * Healthy volunteers: * Regular medication * Abnormal 12-lead electrocardiogram * Abnormal exercise stress test * Patients with coronary disease * Acute coronary syndrome within past 3 months * Impaired left ventricular function * Significant valvular heart disease * Left ventricular hypertrophy * Resting conduction defect * Digoxin use * Renal impairment (eGFR \<60 mL/min) * Hepatic impairment * Asthma

Outcomes

Primary Outcomes

Myocardial blood flow and coronary flow reserve measured by CT/PET O-15 imaging

Myocardial blood flow will be measured at rest and at peak adenosine stress using CT/PET O-15 myocardial perfusion imaging immediately following exposure to diesel exhaust and filtered air

Time frame: Immediately following exposure

Secondary Outcomes

Coronary flow reserve determined using doppler echocardiography

Coronary blood flow will be determined in the left anterior descending coronary artery using doppler echocardiography at rest and at peak adenosine stress 1 hour following exposure to diesel exhaust and filtered air

Time frame: 1 hour following exposure

Ultra-sensitive cardiac troponin-I

Blood samples will be obtained for measurement of cardiac troponin-I

Time frame: Before, 2 and 24 hours following exposure

ST segment deviation on continuous 12-lead electrocardiography

A 12-lead electrocardiogram will be continuously recorded using Holter ECG monitor

Time frame: During and for the 24 hours aftet exposure