UC Irvine

Decreased heart rate variability (HRV) has been observed with long term tobacco use in humans, which is attributed to dysfunction in the autonomic nervous system (ANS)specifically sympathetic nervous system (SNS) dominance and parasympathetic nervous system (PNS) suppression brought about by multiple inflammatory mechanisms. Studies showing these HRV changes tend to analyze both sexes together so sex differentiated responses cannot be identified. HRV changes are well studied in cigarette smoking, but the data looking at alternatives such as hookah smoke is sparse in comparison. Furthermore, while there is data showing signs of persistent ANS dysfunction with chronic exposure, there is no detailed analysis on how these changes develop over time. This study aims to assess if there are sex differentiated responses in overall HRV and recovery changes associated with chronic exposure to hookah smoke (HS) using a mouse model. Methods: Six female and nine male ApoE-/- mice were surgically implanted with radiotelemetry devices. The control group consisted of 4 males and 3 females whereas the exposure group consisted of 5 males and 3 females. A nose-only exposure system was used to deliver purified air to controls and hookah smoke to the exposure groups. Exposures occurred during the day and lasted 2 hours a day for 4 consecutive days followed by 3 days of rest for a total of 20 weeks. HRV measurements were taken in the evening hours after the exposure. Changes in HRV were assessed as percent change from baseline. Average percent change from baseline in heart rate, R-R interval, standard deviation of normal-to-normal intervals, root mean square of successive differences, low frequency (LF), and high frequency (HF) ratio were analyzed for change over time. Further analysis compared each mean change of all metrics between rest and exposure periods using Student’s t test and Mann-Whitney U test. A significance level of p < 0.05 was used for all analyses. Results: The female exposure group was the only group that showed significant signs of SNS dominance in all metrics. The male exposure group showed significant signs of SNS dominance in all metrics except for LF and HF which showed a non-significant trend toward PNS improvement. Both control groups showed signs of stress response with female controls maintaining signs of strong PNS activity over time while males trended toward SNS dominance. Both female groups had more significant differences between rest and exposure metrics in LF, HF and LF/HF ratio in over 50% of the analysis. Both male groups had generally non-significant differences in exposure vs. rest periods.

Overall, these results show sex differentiated response to identical stressors which is not readily explainable based on the available data. A closer look at how males and females differ in levels of sex hormones, cortisol, markers of inflammation and oxidative stress may help explain the underlying mechanisms behind these results.