Science Inventory

Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease

Citation:

Dye, J., A. Ledbetter, M. Schladweiler, D. Costa, AND U. Kodavanti. Whole Body Plethysmography Reveals Differential Ventilatory Responses to Ozone in Rat Models of Cardiovascular Disease. INHALATION TOXICOLOGY. Informa Healthcare USA, New York, NY, 1:14-25, (2015).

Impact/Purpose:

This paper examined the influence of underlying cardiovascular diseases in breathing impairment induced by ozone. Rats with underlying cardiovascular compromise maintained relative hyperpnea when exposed to O3 suggesting that they might recieve significantly greater O3 lung deposition. This can impact the dosimetric consideration for diease models.

Description:

Increasingly, urban air pollution is recognized as an important determinant of cardiovascular disease. Host susceptibility to air pollution can vary due to genetic predisposition and underlying disease. To elucidate key factors of host susceptibility to air pollution, healthy and cardiovascular (CV)-compromised rats were exposed to air or ozone (03) at 0.25, 0.5, or 1.0 ppm for 4 h. We hypothesized that rat strains with the least cardiac reserve would be most prone to develop significant health effects. Using flow whole body plethysmography (FWBP), ventilatory responses in healthy 3-month-old male rats [i.e. Wistar-Kyoto (WKY), Wistar (WIS}, and Sprague­ Dawley (SD) strains] were compared with hypertensive [i.e. spontaneously hypertensive (SH), fawn-hooded-hypertensive (FHH), and SH-stroke-prone (SHSP)] strains and obese [i.e. SH-heart failure-prone (SHHF) and JCR:LA-cp, atherosclerosis-prone (JCR)] strains. SH were slower to acclimate to the FWBP chambers. At 0-h post-air-exposure, SHSP and SHHF exhibited hyperpnea, indicative of cardiopulmonary insufficiency. At O-h-post-03 , all but one strain showed significant concentration-dependent decreases in minute volume [MV = tidal volume (TV) x breathing frequency]. Comparing air with 1.0 ppm responses, MV declined 20-27% in healthy, 21-42% in hypertensive, and 33% in JCR rats, but was unchanged in SHHF rats. Penh increased significantly in all strains, with disproportionate increases in "responder" WKY and FHH strains. By 20 h, most changes had resolved, although Penh remained elevated in WKY, SH, and SHSP. Based on the effective dose estimates (03 ppm x h x MV), the most CV-compromised (SHSP and SHHF) strains received significantly greater 03 lung deposition (25% and 40%, respectively). Data support epidemiologic associations that individuals with cardiopulmonary insufficiency are at greater risk for urban pollutant exposure due, in part, to enhanced lung deposition and exacerbation of hypoxia and pathophysiologic processes of heart failure.

URLs/Downloads:

https://doi.org/10.3109/08958378.2014.954167   Exit

Record Details:

Record Type: DOCUMENT (JOURNAL/PEER REVIEWED JOURNAL)
Product Published Date: 12/15/2015
Record Last Revised: 11/21/2017
OMB Category: Other
Record ID: 311094

Organization:

U.S. ENVIRONMENTAL PROTECTION AGENCY

OFFICE OF RESEARCH AND DEVELOPMENT

NATIONAL HEALTH AND ENVIRONMENTAL EFFECTS RESEARCH LABORATORY

ENVIRONMENTAL PUBLIC HEALTH DIVISION

CARDIOPULMONARY AND IMMUNOTOXICOLOGY BRANCH