Myocardial Ischaemia After Exposure to Diesel Exhaust

Study Overview
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Brief Summary
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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: Myocardial blood flow will be reduced Coronary flow reserve will be impaired The magnitude of impairment will be higher in patients with coronary disease as compared to healthy controls

Official Title
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Myocardial Ischaemia After Exposure to Diesel Exhaust

Conditions
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Coronary Heart Disease

Intervention / Treatment
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* Other: CT/PET Myocardial Perfusion Imaging using O-15 water
* Other: Coronary blood flow measured by doppler echocardiography


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 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: Quadruple


Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Placebo Comparator: Filtered Air Exposure<br>Subjects will be exposed to filtered air for 1 hour during intermittent exercise in a purpose-built exposure facility | Other: CT/PET Myocardial Perfusion Imaging using O-15 water<br> <br> Other: Coronary blood flow measured by doppler echocardiography<br> <br> |
| Experimental: Dilute Diesel Exhaust Exposure<br>Subjects will be exposed to dilute diesel exhaust ( 300 mcg/m3) for 1 hour during intermittent exercise in a purpose-built exposure facility | Other: CT/PET Myocardial Perfusion Imaging using O-15 water<br> <br> Other: Coronary blood flow measured by doppler echocardiography<br> <br> |

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | Immediately following exposure | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| 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 | 1 hour following exposure | 
| Ultra-sensitive cardiac troponin-I | Blood samples will be obtained for measurement of cardiac troponin-I | 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 | During and for the 24 hours aftet exposure | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Air Pollution, Myocardial Ischaemia, Coronary Blood Flow, Diesel Exhaust, Troponin, Electrocardiography