Clinical trial NCT01661582: Myocardial Ischaemia After Exposure to Diesel Exhaust
Official title: Myocardial Ischaemia After Exposure to Diesel Exhaust
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Coronary Heart Disease
Keywords: Air Pollution
Myocardial Ischaemia
Coronary Blood Flow
Diesel Exhaust
Troponin
Electrocardiography
Lead sponsor: University of Edinburgh
Sponsor class: OTHER
Collaborators: name: National Institute for Public Health and the Environment (RIVM)
name: British Heart Foundation
First posted: 2012-08-09
Enrollment: 28
Sex: MALE
Minimum age (years): 18
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: RANDOMIZED
Intervention model: CROSSOVER
Primary purpose: BASIC_SCIENCE

Brief summary: 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


Eligibility criteria: 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

Primary outcomes:
measure: Myocardial blood flow and coronary flow reserve measured by CT/PET O-15 imaging
timeFrame: Immediately following exposure
Secondary outcomes:
measure: Coronary flow reserve determined using doppler echocardiography
timeFrame: 1 hour following exposure
measure: Ultra-sensitive cardiac troponin-I
timeFrame: Before, 2 and 24 hours following exposure
measure: ST segment deviation on continuous 12-lead electrocardiography
timeFrame: During and for the 24 hours aftet exposure
Other outcomes:
Locations:
city: Edinburgh
country: United Kingdom
facility: University of Edinburgh / NHS Lothian
Study officials:
affiliation: University of Edinburgh
name: David E Newby, PhD FRCP
role: STUDY_CHAIR
affiliation: University of Edinburgh
name: Jeremy P Langrish, MB BCh MRCP
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.
citation: 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.