Particulate air pollution is an important public health problem with respect to cardiovascular morbidity and mortality. Important strides have been made in understanding the neural and cardiac mechanisms involved. Heart rate variability analysis revealed important disturbances in autonomic tone during exposure to concentrated air particles (CAPs). We have obtained evidence in our canine models that CAPs may increase the severity of ischemia during acute coronary artery occlusion. These findings provide the direction for our studies, which are intended to expand our understanding of the mechanisms of air particulate exposure on the cardiovascular system.
The specific aims are: 1) To determine the effect of ambient air particles on coronary hemodynamic function and arterial blood pressure in conscious dogs using CAPs exposures. 2) To determine whether the influence of ambient air particles on coronary artery blood flow and resistance is exacerbated by coronary artery stenosis in conscious dogs using CAPs exposures. Our studies will continue to employ the Harvard Ambient Particulate Concentrator (HAPC), a device that can increase ambient particle concentrations up to 30x without changing the physical or chemical characteristics of the particles; 2) a typical urban aerosol; 3) animal models of disease including myocardial ischemia in dogs to simulate the condition of compromised humans with ischemic heart disease, the primary substrate for adult cardiac mortality. The animals will be chronically instrumented with flow probes and telemetry devices to monitor arterial blood pressure and EKG. Coronary blood flow and pressure will be monitored in normal dogs and in dogs with partial coronary artery stenosis and compared during sympathetic or parasympathetic nerve blockade. The vasoactive balance controlled by endothelins and nitric oxide will be assessed during regulation of the coronary vascular response. The effects of components of pollutants will be systematically studied. Thus, the present application will entail unique application of comprehensive techniques to improve understanding of the mechanisms whereby CAPs can exert its deleterious influences on the heart and circulation ? ?

Agency
National Institute of Health (NIH)
Institute
National Institute of Environmental Health Sciences (NIEHS)
Type
Research Project (R01)
Project #
1R01ES012972-01
Application #
6775064
Study Section
Alcohol and Toxicology Subcommittee 4 (ALTX)
Program Officer
Mastin, Patrick
Project Start
2004-09-30
Project End
2009-07-31
Budget Start
2004-09-30
Budget End
2005-07-31
Support Year
1
Fiscal Year
2004
Total Cost
$542,791
Indirect Cost
Name
Harvard University
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
149617367
City
Boston
State
MA
Country
United States
Zip Code
02115
Coull, Brent A (2011) A random intercepts-functional slopes model for flexible assessment of susceptibility in longitudinal designs. Biometrics 67:486-94
Bartoli, Carlo R; Nadar, Menaka M; Godleski, John J (2010) Capsule thickness correlates with vascular density and blood flow within foreign-body capsules surrounding surgically implanted subcutaneous devices. Artif Organs 34:857-61
Bartoli, Carlo R; Godleski, John J (2010) Blood flow in the foreign-body capsules surrounding surgically implanted subcutaneous devices. J Surg Res 158:147-54
Bartoli, Carlo R; Wellenius, Gregory A; Diaz, Edgar A et al. (2009) Mechanisms of inhaled fine particulate air pollution-induced arterial blood pressure changes. Environ Health Perspect 117:361-6
Bartoli, Carlo R; Wellenius, Gregory A; Coull, Brent A et al. (2009) Concentrated ambient particles alter myocardial blood flow during acute ischemia in conscious canines. Environ Health Perspect 117:333-7
Bartoli, Carlo R; Okabe, Kazunori; Akiyama, Ichiro et al. (2008) Repeat microsphere delivery for serial measurement of regional blood perfusion in the chronically instrumented, conscious canine. J Surg Res 145:135-41
Bartoli, Carlo R; Akiyama, Ichiro; Okabe, Kazunori et al. (2008) Permanent tracheostomy for long-term respiratory studies. J Surg Res 145:124-9
Nikolov, Margaret C; Coull, Brent A; Catalano, Paul J et al. (2007) An informative Bayesian structural equation model to assess source-specific health effects of air pollution. Biostatistics 8:609-24
Bartoli, Carlo R; Akiyama, Ichiro; Godleski, John J et al. (2007) Long-term pericardial catheterization is associated with minimum foreign-body response. Catheter Cardiovasc Interv 70:221-7
Bartoli, Carlo R G; Okabe, Kazunori; Akiyama, Ichiro et al. (2006) Technique for implantation of chronic indwelling aortic access catheters. J Invest Surg 19:397-405

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