Cardiovascular Effects of Mountaintop Mining Particulate Matter: Similarities to Shale Gas Development
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1 Cardiovascular Effects of Mountaintop Mining Particulate Matter: Similarities to Shale Gas Development Travis L. Knuckles, Ph.D. Research Assistant Professor Occupational and Environmental Health Sciences School of Public Health West Virginia University
2 Presentation Outline Background: Cardiovascular physiology Cardiovascular effects of inhaled particles Particulate Matter (PM) Methods Study Design Exposure Design Results Conclusions and Future Directions
3 Cardiovascular Disease In 2008, over 616,000 people died of heart disease in the US. Heart disease caused almost 25% of all deaths Heart disease is the leading cause of death for both men and women.
4 Microvasculature
5 Microvasculature The mechanistic consequences of essentially every pathological and developmental state first manifest themselves at the microvascular level. 1) Hypertension 2) Diabetes 3) Obesity 4) Ischemia 5) Growth
6 Particulate matter Air pollution particulate matter (PM) is a physicochemically diverse mixture of minute solid particles or liquid droplets suspended in ambient air. PM is formed through various natural and anthropogenic (man-made) processes such as: wind blown dust, burning of fossil fuels, construction, metal smelting, and mining.
7 Ambient Particulate Matter Size Distribution Source: Brook et al 2004;Circulation.109:
8 Pulmonary Particle Exposure Alters Microvascular Reactivity. Source: Stapleton et al 2011 Microcirculation.
9 Cardiovascular Effects of Inhaled Particles. Vasodilation Vasoconstriction Platelet Activation Plasma Viscosity Clotting Factors Plasma Cytokines Heart Rate Arrhythmias Heart Rate Variability Ischemic Events: Myocardial infarction Stroke Sudden Cardiac Death
10 Mountaintop Mining 4 km
11 Mountaintop Mining
12 Shale Gas
13 Mountaintop Mine 25 miles 1 mile
14 Mountaintop Mine Sampling Sites 20 Miles
15 Central Hypothesis Pulmonary particle exposure alters arteriolar function which results in excess cardiovascular morbidity and mortality.
16 Mountaintop Mining Study Methods Aerosol Characterization Collection of total suspended particulates over several weeks. Extraction of the sample in ultrapure water with agitation. Intratracheal Instillation (IT) of vehicle or vehicle with MTM particles (300 μg/rat in 5% FBS sterile saline).
17 Mountaintop Mining PM (PM MTM ) Mass Number dn/dlogdp (10 4 /cm 3 ) dm/dlogdp ( g/m 3 ) Particle Diameter (nm) 0
18 Mountaintop Mining PM (PM MTM ) 40 μm
19 Particle Counts
20 Mountaintop Mining PM (PM MTM )
21 Mountaintop Mining Study Methods 24 hours post IT exposure (SD rats 7-10 weeks) -Arteriolar Reactivity Intravital microscopy Intraluminal Infusion Perivascular Nerve Stimulation Active Hyperemia Isolated Vessels Endothelium-dependent dilation. Endothelium-independent dilation Arteriolar constriction
22 Sham PM MTM
23 PM MTM Inhibits Endothelium-Dependent Arteriolar Dilation
24 PM MTM Alters In Vivo Arteriolar Responses to Endogenously Produced Dilators/Constrictors
25 PM MTM Inhibits Endothelium-Dependent Arteriolar Dilation
26 Conclusions Pathology indicates an hypertrophic/hyperproliferative BALT, with excessive lymphocytes invading and disrupting the smooth muscle..visible alveolar condensation and collapse due to the lymphocytic proliferation most likely due to a chronic inflammatory response. The results indicate that PM MTM induces a microvascular dysfunction that could contribute to cardiovascular morbidity and mortality through reduced responsiveness to vasodilatory signals.
27 Future Directions Lung pathology Study with USGS Carcinogenesis study (Yon Rojanasakul s Lab) Cardiac functional and Mitochondrial analysis (John Hollander s Lab) Mechanisms of altered microvascular function.
28 Acknowledgements Michael McCawley Ph.D. Tim Nurkiewicz's Lab: Carroll McBride Valarie Minarchick Phoebe Stapleton, Ph.D. Laura Kurth, Ph.D. USGS Lynn Crosby, Ph.D. Bill Orem, Ph.D. Michael Hendryx, Ph.D. John Hollander s Lab: Cody Nichols Danielle Shepard Yon Rojanasakul s Lab: Suidjit Luanpitpong, Ph.D.
29 Cherng et al AJP Reg. Int Comp Phys
30 Knuckles et al. Toxicology and Applied Pharmacology 230 (2008)
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