Effects of subchronic exposures to concentrated ambient particles (CAPs) in mice: III. Acute and chronic effects of CAPs on heart rate, heart-rate fluctuation, and body temperature

Normal mice (C57) and mice prone to develop atherosclerosis (ApoE(-/-)) were implanted with electrocardiograph (EKG), core body temperature, and motion transmitters and were exposed daily for 6 h to Tuxedo, NY, concentrated ambient particles (CAPs) for 5 days/wk during the spring and summer of 2003. Time series of 5-min EKG monitoring and body-temperature measurements were obtained for each animal in the CAPs and filtered air sham exposure groups. Our hypothesis was that chronic exposure could cause cumulative health effects. We used our recently developed nonparametric method to estimate the daily time periods that mean heart rates (HR), body temperature, and physical activity differed significantly between the CAPs and sham exposed groups. CAPs exposure most affected heart rate between 1:30 a.m. and 4:30 a.m. With the response variables being the average heart rate, body temperature, and physical activity, we adopted a two-stage modeling approach to obtain the estimates of chronic and acute effects on the changes of these three response variables. In the first stage, a time-varying model estimated daily crude effects. In the second stage, the true means of the estimated crude effects were modeled with a polynomial function of time for chronic effects, a linear term of daily CAPs exposure concentrations for acute effects, and a random component for unknown noise. A Bayesian framework combined these two stages. There were significant decreasing patterns of HR, body temperature, and physical activity for the ApoE(-/-) mice over the 5 mu of CAPs exposure, with smaller and nonsignificant changes for the C57 mice. The chronic effect changes of the three response variables for ApoE(-/-) mice were maximal in the last few weeks. There was also a significant relationship between CAPs exposure concentration and short-term change of heart rate in ApoE(-/-) mice during exposure. Response variables were also defined for examining fluctuations of 5-min heart rates within long (i.e., 3-6 h) and short time periods (i.e., similar to 15 min). The results for the ApoE(-/-) mice showed that heart-rate fluctuation within the longer periods increased to 1.35-fold by the end of exposure experiment, while the heart-rate fluctuation within 15 min decreased to 0.7-fold.