Firefighters and acute myocardial infarction : understanding mechanisms and reducing risk

3 LAY SUMMARY . 7 TABLE OF CONTENTS . 11 TABLE OF FIGURES . 17 TABLE OF TABLES . 19 DECLARATION . 20 ACKNOWLEDGEMENTS . 22 ABBREVIATIONS . 26 CHAPTER 1: INTRODUCTION . 30 1.1 OVERVIEW . 30 1.2 PRE-EXISTING RISK FACTORS FOR CARDIOVASCULAR DISEASE . 33 1.2.1 Firefighter Fitness . 34 1.2.2 Obesity . 40 1.2.3 Age . 41 1.2.4 Traditional cardiovascular risk factors . 42 1.2.5 Pre-existing Coronary Artery Disease . 44 1.3 TRIGGERS FOR MYOCARDIAL INFARCTION IN FIREFIGHTERS . 47 1.3.1 Extreme Physical Exertion . 47 1.3.2 Heat Stress: Increased core body temperature . 50 1.3.3 Psychological Stress . 53 1.3.4 Air Pollution . 55 1.4 EVOLUTION OF CARDIOVASCULAR EVENTS IN FIREFIGHTERS . 65 1.4.1 Pathogenesis of Atherothrombosis . 65 1.4.2 Acute cardiovascular strain of firefighting . 69 1.4.3 The impact of air pollution relating to firefighters . 76 1.4.4 The Final common pathway leading to cardiovascular events . 82 Firefighters and Acute Myocardial Infarction: Understanding Mechanisms and Reducing Cardiovascular Risk 12 1.5 AIMS AND HYPOTHESIS . 83 CHAPTER 2: METHODS . 85 2.1 SUBJECT RECRUITMENT . 85 2.1.1 Ethical Considerations . 85 2.1.2 Healthy Volunteer Firefighters and Police Officers . 85 2.2 EXPOSURES . 87 2.2.1 Woodsmoke exposure . 87 2.2.2 Fire simulation exposures . 90 2.3 VASCULAR STUDIES . 93 2.3.1 Venous occlusion plethysmography . 94 2.3.2 Brachial artery cannulation . 96 2.3.3 Venous blood sampling . 96 2.3.4 Intra-arterial vasoactive mediators . 98 2.3.5 Plethysmography data analysis . 99 2.4 ASSESSMENT OF THROMBOSIS . 101 2.4.1 Badimon Chamber . 101 2.4.2 Flow cytometry . 109 2.4.3 In vivo fibrinolysis . 110 2.5 VENOUS ASSAYS . 112 2.5. 1 Sample preparation and processing . 112 2.5. 2 High sensitivity cardiac troponin I . 113 2.6 MONITORING . 114 2.6. 1 Blood pressure monitoring and analysis . 114 2.6. 2 Electrocardiographic monitoring and analysis . 114 2.6. 3 Core body temperature monitoring . 115 2.7 CARDIOPULMONARY EXERCISE TESTING . 116 2.8 DATA ANALYSIS AND STATISTICS . 116 CHAPTER 3: COMPARISON OF VASCULAR FUNCTION AND CARDIOVASCULAR RISK IN EMERGENCY SERVICE PROFESSIONALS . 119 3.1 SUMMARY . 119 3.2 INTRODUCTION . 121 Firefighters and Acute Myocardial Infarction: Understanding Mechanisms and Reducing Cardiovascular Risk 13 3.3 METHODS . 123 3.3.1 Study participants . 123 3.3.2 Study design . 123 3.3.3 Ex-vivo thrombus studies . 127 3.3.4 Vasomotor and fibrinolytic studies . 127 3.3.5 Data analysis and statistics . 127 3.4 RESULTS . 128 3.4.1 Cardiovascular risk profiles . 128 3.4.2 Thrombus formation . 131 3.4.3 Vascular vasomotor and fibrinolytic function . 131 3.5 DISCUSSION . 134 3.6 CONCLUSION . 145 CHAPTER 4: EFFECT OF WOOD SMOKE EXPOSURE ON VASCULAR FUNCTION AND THROMBUS FORMATION IN HEALTHY FIREFIGHTERS . 147 4.1 SUMMARY . 147 4.2 INTRODUCTION . 149 4.3 METHODS . 151 4.3.1 Study population . 151 4.3.2 Study design . 151 4.3.3 Wood smoke exposure . 153 4.3.4 Polycyclic aromatic hydrocarbon analysis . 154 4.3.5 Electron paramagnetic resonance . 155 4.3.6 Arterial stiffness . 156 4.3. 7 Vascular studies . 157 4.3. 8 Flow cytometry . 157 4.3. 9 Ex-vivo thrombosis studies . 157 4.3.10 Data analysis and statistics . 157 4.4 RESULTS . 159 4.4.1 Haematology . 164 4.4.2 Arterial stiffness and vascular function . 164 4.4.3 Platelet activation and thrombosis . 169 4.5 DISCUSSION .