The cardiac mechanisms responsible for increased mortality due to exposure to particulate air pollution have not been adequately defined. This proposal is designed to increase our understanding of this important public health problem by employing state-of-the-art spectral eCG analysis in well-established models of ischemic heart disease. Sleep states as well as wakefulness will be investigated because pollution-induced release of cytokines can result in excess slow wave sleep. This is especially important since somnolence is associated iwth greater propensity to cardiorespiratory disturbances including apneas. The attendant deleterious impact on oxygen delivery to the myocardium could constitute an intermediary mechanism leading to environmentally induced arrhythmias and infarction due to direct myocardial effects or through cytokine-induced changes in central nervous system activity and autonomic tone.
Specific aims are: 1) To assess mortality and morbidity from exposure to concentrated air particles (CAPs) in normal adult dogs during wakefulness and sleep; 2) To evaluate the potential role of autonomic nervous system activation in vulnerability to cardiac arrhythmias during exposure to air pollutants; and 3) To define the influence of exposure to ambient air particles on cardiac vulneraability during acute myocardial ischemia and infarction. Our studies will utilize The Harvard Ambient Particulate Concentrator (HAPC), a newly developed 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 with transported sulfur-containing acidic particles during the summer and local combustion product particulate in winter; 3) Animal models of disease including myocardial ischemia and infarction in dogs to model compromised human populations and to elucidate mechanistic effects; 4) Established cell and molecular biology methods to test mechanistic hypotheses on the role of pro-inflammatory chemokines in thedevelopment of morbidity and mortality; and 5) Established cardiac measures including arrhythmias and ST-segment changes. In addition, dynamic tracking of cardiac vulnearability by complex demodulation will be used to asses T-wave alternans, a beat-to-beat fluctuation in amplitude of the T-wave, which has recently been shown to provide a noninvasive index of vulnerability to life-threatening arrhythmias. The unique application of these comprehensive techniques will offer new insights into the mechanisms whereby ambient air particles exert their cardiotoxic effects.
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