title: In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias.
abstract: Exposure to ultrafine particles (UFPs) by inhalation increases the number and severity of cardiac events. The specific mechanism(s) of action are unknown. This study was designed to examine whether UFPs could exert a direct effect on the cardiovascular system without dependence upon lung-mediated responses. The direct effects of UFPs were determined in normal rats (infused intravenously with UFPs), and in the isolated Langendorff perfused rat heart. UFPs from either ambient air (UFAAs) or diesel engine exhaust (UFDGs) were studied. Infusion of UFDGs prepared in our laboratory caused ventricular premature beats (VPBs) in 2 of 3 rats in vivo. Ejection fraction increased slightly (approximately 4.5%) in rats receiving UFPAA and was unchanged in the UFDG and saline groups in vivo. In the isolated rat heart, perfused according to Langendorff, UFDGs caused a marked increase in left-ventricular end-diastolic pressure (LVEDP; from 12.0 +/- 4.6 mmHg to 24.8 +/- 11.2 mmHg, p < 0.05) after 30 min of exposure. UFPs isolated from industrial diesel particulate matter (UFIDs), obtained from the National Institute of Standards and Technology, caused a significant decrease in left-ventricular systolic pressure (LVSP; from 85.7 +/- 4.0 mmHg to 37.9 +/- 20.3 mmHg, p < 0.05) and +/- dP/dt (from 2,365 +/- 158 mmHg/s to 1,188 +/- 858 mmHg/s, p < 0.05) at 30 min after the start of infusion. This effect was absent when the soluble fraction (containing no particles) isolated from the UFIDs was studied. These findings indicate that UFPs can have direct effects on the cardiovascular system that are independent of effects of particles on the lungs.
authors.affiliation: The Heart Institute, Good Samaritan Hospital, Los Angeles, CA 90017, USA.
authors.forename: Loren E
authors.initials: LE
authors.lastname: Wold
authors.forename: Boris Z
authors.initials: BZ
authors.lastname: Simkhovich
authors.forename: Michael T
authors.initials: MT
authors.lastname: Kleinman
authors.forename: Margaret A
authors.initials: MA
authors.lastname: Nordlie
authors.forename: Joan S
authors.initials: JS
authors.lastname: Dow
authors.forename: Constantinos
authors.initials: C
authors.lastname: Sioutas
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kloner
mesh_terms: D000393:Air Pollutants / Q000633:toxicity*; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000139:chemically induced* / Q000503:physiopathology; D005260:Female; D006321:Heart / Q000187:drug effects* / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D007275:Injections, Intravenous; D010477:Perfusion; D051381:Rats; D017207:Rats, Sprague-Dawley; D001335:Vehicle Emissions / Q000633:toxicity*; D018487:Ventricular Dysfunction, Left / Q000139:chemically induced / Q000503:physiopathology
chemical_list: D000393:Air Pollutants; D001335:Vehicle Emissions