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Elevation of serum endothelins and cardiotoxicity induced by particulate matter (PM2.5) in rats with acute myocardial infarction
Authors:Kang Y James  Li Yan  Zhou Zhanxiang  Roberts Andrew M  Cai Lu  Myers Steven R  Wang Lipeng  Schuchke Dale A
Affiliation:(1) Department of Physiology, University of Louisville School of Medicine, 40292 Louisville, KY;(2) Department of Pharmacology, and Toxicology, University of Louisville School of Medicine, 40292 Louisville, KY;(3) Jewish Hospital Heart and Lung Institute, 40292 Louisville, KY;(4) Department of Medicine, University of Louisville, School of Medicine, 511 S. Floyd Street, MDR 530, 40202 Louisville, KY
Abstract:Epidemiological studies have defined a significant positive association of acute exposure to ambient concentrations of particulate matter (PM) with increased daily mortality and hospital admission for cardiovascular diseases. Experimental studies have shown that animals with pre-existing cardiovascular diseases are more susceptible to the cardiac effect of PM exposure. The present study was undertaken to investigate possible involvement of upregulation of the endothelin system in PM exposure-induced cardiotoxicity in rats with acute myocardial infarction (MI). Adult male Sprague-Dawley rats were subjected to occlusion of the left coronary artery and displayed myocardial infarction 12 h after the surgery. The heart rate significantly decreased and premature ventricular complexes of the electrocardiogram occurred in the myocardial infarct animals. Exposure to PM2.5 via intratracheal instillation with 2.0 mg in 0.3 mL normal saline significantly worsened the ventricular arrhythmia along with a further decrease in heart rate. The same PM exposure only caused slight cardiac changes in the sham-operated animals. Serum total endothelin concentrations were significantly elevated in both myocardial infarct rats and sham-operated controls in response to PM exposure. However, increased numbers of the endothelin receptor type A on the cardiomyocytes were observed only in the infarct myocardium. This study thus suggests that upregulation of the endothelin system in rats with MI is likely involved in the PM exposure-induced cardiotoxicity.
Keywords:Cardiac arrhythmia  electrocardiogram  endothelin receptor  myocardial infarction  particulate matter
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