Citation:

Dye, J., E. Stewart, A. Ledbetter, AND C. Miller. Carbon dioxide challenge enhances the sensitivity of whole body plethysmography (WBP) measurements of lung growth and ozone-induced changes in juvenile Long-Evans rats. EB2018 (Experiemental Biology), San Diego, California, April 21 - 25, 2018.

Impact/Purpose:

We propose to utilize our recent model of early life environmental stress to examine developmental origins of asthma later in life. Therefore, in this pilot study, we sought to improve the sensitivity of WBP to monitor lung volume growth in rats during development.

Description:

Background. Risk factors associated with development of childhood disorders such as asthma and obesity include prematurity and intrauterine growth restriction. We recently demonstrated that exposure of Long Evans rats in early pregnancy to the air pollutant, ozone, resulted in re-duced near-term fetal growth. We propose to utilize this model of early life environmental stress to examine developmental origins of asthma later in life. Therefore, in this pilot study, we sought to improve the sensitivity of WBP to monitor lung volume growth in rats during development. Methods. Subset A male and female offspring from air- or 0.8 ppm ozone-exposed dams (4h/day on gestational day 5 and 6) (n  6/group) were monitored weekly from postnatal day (PND) 13 to PND70 for changes in body weight and spontaneous ventilatory parame¬ters [i.e., breathing frequency (f), tidal volume (TV), minute volume (MV), EF50 and Penh]. Data were first obtained using mouse and later rat WBP chambers with EMKA iox 2 software (SCIREQ, Montreal, Can-ada). To enhance tidal breathing, Subset B male offspring (n = 7; ≥ PND50) were used to opti-mize a CO2 challenge protocol (5–7.5% CO2) for up to 10 minutes under control conditions, and then later (PND81) to assess whether the CO2 challenge would also be tolerated acutely follow-ing exposure to ozone (0.4 or 0.8 ppm x4h). Results. Subset A offspring underwent rapid growth during the 8-week study period with nearly 15-fold increases in body weight in males and 10-fold increases in females. Corresponding in-creases in TV (~0.2 to > 2.0 mL) were observed. In Subset B males, a 6% CO2 challenge for 6 minutes appeared optimal. Likewise, in Subset A rats at PND67, this CO2 challenge resulted in more uniform breathing, less movement-related artifacts, and increased ventilatory effort (TV increased ~50%); although females were somewhat less responsive. Lastly, use of the 6% CO2 challenge immediately following ozone exposure of Subset B males more readily distinguished the resultant breathing pattern alterations and lung volume deficits occurring. Conclusions. Although the CO2-enhanced lung volume measurements obtained herein are not equivalent to maximal, expiratory maneuvers (i.e., FEV1) as can be achieved in humans, this pro-tocol was well tolerated and may provide a more sensitive, yet non-invasive method of docu-menting differential lung growth trajectories in offspring with or without prior in utero ozone exposure  as they undergo additional exposures during weanling and peri-adolescent life stag-es. (Abstract does not reflect USEPA policy).

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