Environmentally relevant secondhand smoke and time‐dependent changes in cardiovascular regulation in mice

Abstract

BACKGROUND Secondhand smoke (SHS), a significant source of indoor air pollution, is a significant risk factor for cardiovascular morbidity and mortality. SHS-induced autonomic dysfunction, evidenced as increased sympathetic nerve activity and decreased heart rate variability (HRV), has been implicated as an important underlying mechanism for cardiovascular consequences. Previously, we have demonstrated that acute exposure (3 d) to 30 mg/m3 of SHS was sufficient to reduce HRV in mice. Here, we sought to characterize the time course of SHS-induced changes to cardiovascular regulation resulting from chronic exposure to environmentally relevant SHS (3 mg/m3). METHODS Male C57BL/6J mice (11 wk) implanted with BP/ECG telemetry devices were exposed to either filtered air (FA, n=18) or SHS (3 mg/m3, 6 hr/d, 5 d/wk, n=17) for 12 weeks, followed by 4 weeks of FA (representing a SHS “recovery” window). Monthly, 36 hours of continuous BP and ECG recordings were obtained during non-exposure days. Data were divided into three 12-hour periods: The dark cycle (dark 1) immediately after the 5th day of exposure, and the following light and dark (dark 2) cycles. Spontaneous baroreflex sensitivity (BRS) was determined with the sequence method. Standard time domain HRV parameters were obtained during periods of low activity. RESULTS SHS decreased overall HRV (SDNN) during the dark 1 cycle (-15%, -7%, and -28% for 4, 8, and 12 wk, respectively, p < 0.05). Similarly, SHS significantly reduced short-term HRV (rMSSD) during the dark 1 cycle (-16%, -12%, and -20% for 4, 8, and 12 wk, respectively, p < 0.05). SHS exposure did not affect HRV beyond the initial 12 hours after exposure ended (light and dark 2 cycles). These data suggest that SHS attenuates cardiac vagal regulation. SHS also reduced pulse pressure (~2 mmHg, p < 0.05) for the entire 36-hr recording window after 4, 8, and 12 wks of exposure, an effect that persisted even after 4 wks of recovery. There was a trend for lower BRS after 12 wks of SHS exposure during the dark 1 cycle. Intriguingly, initial exposure to SHS significantly elevated diastolic BP (~3 mmHg) during the dark 1 cycle at 4 wks; this effect was not observed with longer exposure to SHS (8 or 12 wks). Taken together, these data suggest that SHS exposure poses a greater risk to cardiac function than vascular function, and that vasculature regulation may be more protected from SHS-induced autonomic effects. CONCLUSIONS Chronic SHS reduces autonomic regulation of the cardiovascular function, particularly the regulation of the heart. Except for reduced pulse pressure, these autonomic effects were transient, and reversed themselves in the absence of SHS exposure, underscoring the importance and efficacy of public smoking bans.