title: Particulate matter inhalation exacerbates cardiopulmonary injury in a rat model of isoproterenol-induced cardiomyopathy.
abstract: Ambient particulate matter (PM) exposure is linked to cardiovascular events and death, especially among individuals with heart disease. A model of toxic cardiomyopathy was developed in Spontaneously Hypertensive Heart Failure (SHHF) rats to explore potential mechanisms. Rats were infused with isoproterenol (ISO; 2.5 mg/kg/day subcutaneous [sc]), a beta-adrenergic agonist, for 28 days and subsequently exposed to PM by inhalation. ISO induced tachycardia and hypotension throughout treatment followed by postinfusion decrements in heart rate, contractility, and blood pressures (systolic, diastolic, pulse), and fibrotic cardiomyopathy. Changes in heart rate and heart rate variability (HRV) 17 days after ISO cessation indicated parasympathetic dominance with concomitantly altered ventilation. Rats were subsequently exposed to filtered air or Harvard Particle 12 (HP12) (12 mg/m(3))--a metal-rich oil combustion-derived PM--at 18 and 19 days (4 h/day) after ISO infusion via nose-only inhalation to determine if cardio-impaired rats were more responsive to the effects of PM exposure. Inhalation of PM among ISO-pretreated rats significantly increased pulmonary lactate dehydrogenase, serum high-density lipoprotein (HDL) cholesterol, and heart-to-body mass ratio. PM exposure increased the number of ISO-pretreated rats that experienced bradyarrhythmic events, which occurred concomitantly with acute alterations of HRV. PM, however, did not significantly affect mean HRV in the ISO- or saline-pretreated groups. In summary, subchronic ISO treatment elicited some pathophysiologic and histopathological features of heart failure, including cardiomyopathy. The enhanced sensitivity to PM exposure in SHHF rats with ISO-accelerated cardiomyopathy suggests that this model may be useful for elucidating the mechanisms by which PM exposure exacerbates heart disease.
authors.affiliation: Environmental Sciences and Engineering, UNC Gillings School of Global Public Health, Chapel Hill, North Carolina, USA.
authors.forename: Alex P
authors.initials: AP
authors.lastname: Carll
authors.forename: Najwa
authors.initials: N
authors.lastname: Haykal-Coates
authors.forename: Darrell W
authors.initials: DW
authors.lastname: Winsett
authors.forename: William H
authors.initials: WH
authors.lastname: Rowan
authors.forename: Mehdi S
authors.initials: MS
authors.lastname: Hazari
authors.forename: Allen D
authors.initials: AD
authors.lastname: Ledbetter
authors.forename: Abraham
authors.initials: A
authors.lastname: Nyska
authors.forename: Wayne E
authors.initials: WE
authors.lastname: Cascio
authors.forename: William P
authors.initials: WP
authors.lastname: Watkinson
authors.forename: Daniel L
authors.initials: DL
authors.lastname: Costa
authors.forename: Aimen K
authors.initials: AK
authors.lastname: Farraj
mesh_terms: D000318:Adrenergic beta-Agonists / Q000633:toxicity*; D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D009202:Cardiomyopathies / Q000139:chemically induced* / Q000473:pathology / Q000503:physiopathology; D004195:Disease Models, Animal; D004357:Drug Synergism; D006321:Heart / Q000187:drug effects; D006333:Heart Failure / Q000139:chemically induced / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D019570:Inhalation Exposure; D007279:Injections, Subcutaneous; D007545:Isoproterenol / Q000008:administration & dosage / Q000633:toxicity*; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D008075:Lipoproteins, HDL / Q000097:blood; D008168:Lung / Q000187:drug effects / Q000201:enzymology; D008297:Male; D009206:Myocardium / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D052638:Particulate Matter / Q000633:toxicity*; D051381:Rats; D011918:Rats, Inbred SHR; D013686:Telemetry
chemical_list: D000318:Adrenergic beta-Agonists; D000393:Air Pollutants; D008075:Lipoproteins, HDL; D052638:Particulate Matter; D007770:L-Lactate Dehydrogenase; D007545:Isoproterenol