Particle Effects on Heart-Rate Regulation in Senescent Mice

Abstract

Because epidemiology studies consistently identify the elderly at risk for air pollution-related morbidity and mortality, we developed a model of senescent-dependent susceptibility based on indices of physiological aging. In the current study, we hypothesized that heart-rate regulation during particulate matter (PM) exposure differs with senescence-dependent susceptibility owing to variation in autonomic nervous control. Heart rate (HR) and heart-rate variability (HRV) parameters were measured from 162 samples of 2-min electrocardiograph (ECG) recordings in age-matched healthy (n = 5) and terminally senescent (n = 3) AKR mice during 3-h exposures to filtered-air (FA, day 1) and carbon black (CB, day 4; < 200 μ g/m³). On day 1, HR was significantly (p <. 01) depressed during FA in terminally senescent mice. By day 4, HR was further slowed significantly (p <. 01) due to the effects of CB exposure for 3 days. The combined effects of terminal senescence and CB exposure acted to depress HR to an average (±SEM) 445 ± 40 bpm, or ∼ 80 bpm lower compared to healthy HR responses. The change in rMSSD, an HRV parameter corresponding to relative influences of parasympathetic tone on HR, was significantly (p <. 01) greater on day 1 and day 4 in terminally senescent mice compared to healthy mice. In contrast, the LF/HF ratio, an HRV parameter derived from spectral analysis indicating relative changes in cardiac sympathetic tone, was significantly (p <. 01) depressed in terminally senescent mice on day 1. By day 4, significant increases in LF/HF were evident in healthy mice during CB exposure, suggesting that HR regulation was associated with an increase in sympathetic tone. Alternatively, terminally senescent mice appeared to modulate a lower HR without change in LF/HF ratio during CB exposure, suggesting an absence of sympathetic tone. In conclusion, older healthy mice increase cardiac sympathetic tone during PM exposure while terminally senescent mice show a greater PM-induced parasympathetic tone in regulating HR. The significance of the current results suggest that PM-induced HR regulatory changes may ultimately depend on the degree of physiological aging.

This study was supported by the Electric Power Research Institute (WO8203-01) and National Institutes of Health, grant AG-21057.