Myocardial Ischaemia After Exposure to Diesel Exhaust (MIDAS)

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

Air Pollution, Myocardial Ischaemia, Coronary Blood Flow, Diesel Exhaust, Troponin, Electrocardiography

Subjects will be exposed to filtered air for 1 hour during intermittent exercise in a purpose-built exposure facility

Subjects will be exposed to dilute diesel exhaust (~300 mcg/m3) for 1 hour during intermittent exercise in a purpose-built exposure facility

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

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

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

Mills NL, Tornqvist H, Gonzalez MC, Vink E, Robinson SD, Soderberg S, Boon NA, Donaldson K, Sandstrom T, Blomberg A, Newby DE. Ischemic and thrombotic effects of dilute diesel-exhaust inhalation in men with coronary heart disease. N Engl J Med. 2007 Sep 13;357(11):1075-82. doi: 10.1056/NEJMoa066314.

Langrish JP, Watts SJ, Hunter AJ, Shah AS, Bosson JA, Unosson J, Barath S, Lundback M, Cassee FR, Donaldson K, Sandstrom T, Blomberg A, Newby DE, Mills NL. Controlled exposures to air pollutants and risk of cardiac arrhythmia. Environ Health Perspect. 2014 Jul;122(7):747-53. doi: 10.1289/ehp.1307337. Epub 2014 Mar 25.