Four weeks of exposure to environmentally relevant levels of second hand smoke decreases heart rate variability—but not baroreflex sensitivity—in mice

Abstract

BACKGROUNDSecond hand smoke (SHS), a source of environmental air pollution exposure, is a significant risk factor for cardiovascular morbidity and mortality. Impaired autonomic function, as indexed by decreased heart rate variability (HRV), has been implicated as one of the underlying mechanisms of increased arrhythmia susceptibility that often precedes sudden cardiac death. We previously showed, in mice, that short term (3 days) exposure to a high level of SHS (30 mg/m3, 6 hr/d) reduced HRV that persisted after this acute window of SHS exposure. However, we have limited information on the time course of SHS‐induced cardiovascular dysfunction at more environmentally relevant concentrations. Here, we sought to test the hypothesis that an environmentally relevant level of SHS decreases HRV and baroreflex sensitivity (BRS), while increasing blood pressure (BP) and BP variability (BPV).METHODSAdult male C57BL/6J mice were implanted with BP/ECG telemetry devices. Two weeks after recovering from surgery, mice were randomly assigned to either filtered air (FA, n=10 for HRV, n=5 for BPV and BRS) or SHS (n=6) groups. SHS exposure level was similar to that of a “smoky bar” (3 mg/m3) for 6hr/d, 5d/wk for 4wk. Weekly, 36 hours of continuous BP and ECG recordings were performed after five days of exposure. Data were divided into three 12‐hour periods: the dark cycle immediate after the 5th day of exposure and the following light and dark cycles. Standard time domain HRV parameters were determined from normal‐to‐normal R wave intervals (SDNN, CV% and rMSSD). BRS was determined with the sequence method using systolic BP.RESULTSSHS exposure for four weeks did not change BP and HR in either dark or light cycle. SHS significantly decreased short term HRV (rMSSD) during the light cycle in as few as two weeks of exposure (28% lower than FA group, p<0.05). However, there was no significant change in overall HRV (SDNN and CV%) after four weeks of SHS exposure. These data suggest that the initial change in cardiac autonomic regulation is likely mediated by reduced vagal regulation. There was a trend, but not statistically significant effect, for an increase in BPV (12% higher than FA group) after four weeks of SHS exposure; however, no change in BRS was observed after four weeks of SHS exposure. These data suggest that changes in cardiac regulation precede changes in BP regulation, and that the cardiac vagal limb of the autonomic nervous system is particularly sensitive to SHS exposure.CONCLUSIONSWe conclude that this environmentally relevant dose of SHS can impair cardiovascular regulation in a time‐dependent manner, further emphasizing the importance of regulating and limiting exposure to SHS.Support or Funding InformationR01 ES025229; T32 HL086350