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In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias

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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 in creased slightly (∼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 ncrease 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 2365±158 mmHg/s to 1188±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.

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Authors and Affiliations

  1. Division of Cardiovascular Medicine, Kech School of Medicine, University of Southern California, Los Angeles

    Boris Z. Simkhovich & Robert A. Kloner MD, PhD

  2. Community and Environmental Medicine, University of California-Irvine, Irvine

    Michael T. Kleinman

  3. Department of Civil Engineering, University of Southern California, Los Angeles, CA

    Constantinos Sioutas

  4. Division of Mathematics and Natural Sciences, University of Mary, Bismarck, ND

    Margaret A. Nordlie

  5. The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, 90017, Los Angeles, CA

    Loren E. Wold, Boris Z. Simkhovich, Joan S. Dow & Robert A. Kloner MD, PhD

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  1. Loren E. Wold
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  2. Boris Z. Simkhovich
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Wold, L.E., Simkhovich, B.Z., Kleinman, M.T. et al. In vivo and in vitro models to test the hypothesis of particle-induced effects on cardiac function and arrhythmias. Cardiovasc Toxicol 6, 69–78 (2006). https://doi.org/10.1385/CT:6:1:69

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