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USE OF WHOLE BODY PLETHSYMOGRAPHY TO ASSESS INFLUENCES OF RAT STRAIN AND AGE ON NONSPECIFIC AIRWAY RESPONSIVENESS
Citation:
Dye, J A., D. W. Winsett, AND D L. Costa. USE OF WHOLE BODY PLETHSYMOGRAPHY TO ASSESS INFLUENCES OF RAT STRAIN AND AGE ON NONSPECIFIC AIRWAY RESPONSIVENESS. Presented at Symposium on Lung Injury Repair, Montreal, Quebec, Canada, Sept 30-October 3, 2004.
Description:
Increased airway responsiveness (AR) is a well-established characteristic of asthma that epidemiological evidence suggests may be linked to air pollutant exposure. Establishing the biologic basis between pollutant exposure and subsequent adverse public health outcome requires an integrated toxicological approach - a key component of which is the ability to quantify pollutant-induced changes in pulmonary physiology and AR in laboratory species. Increasingly, whole body plethysmography (WBP) is being used to "document" air pollutant effects. This is due in part to its ability to allow non-invasive, repeated assessment of the breathing pattern/ventilatory effort of unrestrained, untrained animals. Therefore, in these studies we examined: (1) whether rat strain-related differences in AR could be determined using the WBP-based enhanced pause ("Penh", a unitless parameter) during stepped aerosolized methacholine (MCh) bronchoprovocation testing, and (2) whether age further influenced this assessment. The strains evaluated included 4 commonly used in air pollutant research, namely outbred Sprague-Dawley (CD), Wistar-Kyoto (WKY), spontaneously hypertensive (SH), and "atopy-prone" Brown-Norway (BN) rats. Results demonstrated that strain differences in AR to MCh were apparent in young adult (4-mo-old) male rats with: CD?WKY>SH?BN. These results were consistent with previous AR assessments in anesthetized, intubated, and ventilated 4-mo-old WKY and SH rats based on changes in airway opening pressure during IV acetylcholine challenge. Lastly, assessment of the effects of aging on AR in CD rats using WBP/Penh revealed relatively minor influences with the following overall pattern: 8-mo-old > 4-mo-old ? 17-mo-old ? 24-mo-old rats. Similarly, in SH rats, AR to MCh in 8-mo-old > 17-mo-old > 4-mo-old rats. We conclude that while WBP is seemingly sufficiently sensitive to evaluate AR non-invasively in rats, prudent use of appropriate strain- and age-matched controls will be critical to interpreting and extrapolating air pollutant-induced effects on AR in laboratory rats.
(This abstract does not reflect US EPA policy).