A Thermoneutral Environment Abolishes Age‐Associated Reduction in Heart Rate Variability in Mice

Background Current dogma suggests sympathetic tone is the dominant regulator of rodent heart function at standard laboratory ambient temperature (LT A ). Recent studies have shown, however, the high surface area to body mass ratio of rodents forces them to use non‐shivering thermogenesis driven by sympathetic stimulation of brown fat to maintain proper thermoregulation at LT A , raising heart rate (HR). When mice are studied at their thermoneutral ambient temperature (NT A ) there is a decrease in HR and a formidable vagal component to HR regulation is revealed. HR regulation can be described by heart rate variability (HRV), a group of parameters which quantify the variation of beat‐to‐beat intervals. Additionally, HRV becomes reduced in advanced age due to reduced parasympathetic input. Objective To unravel the impact of autonomic input on age‐associated changes in HR and HRV over a range of ambient temperatures. Methods HR was measured in young (3 mo) and aged (30 mo) male C57/BL6 telemetry‐implanted mice via in‐vivo ECG after a 3‐day acclimation period at 20ºC. Another ECG was recorded after a 3‐day acclimation period at 30ºC. HRV was evaluated in both time and frequency domains extrapolated from ECG recordings. Data was analyzed using linear mixed effects models. The double interaction term (temperature and age) in the models was used to evaluate the effect of temperature on HR and HRV by age group while correcting biases stemming from repeated measurements and uneven group sizes. Results Changing the ambient temperature altered mean HR of both age groups and several HRV indices in the aged mice. Mean HR of young mice was 595 ± 23 beats per minute (bpm) at 20ºC and decreased to 367 ± 14 bpm at 30ºC (p < 0.0001). Mean HR of aged mice was 622 ± 9.0 bpm at 20ºC and decreased to 323 ± 23 bpm at 30ºC (p < 0.0001) (Figure 1). Coefficient of variance (CV), an indicator of overall time‐domain HRV, was significantly reduced in old mice (2.24 ± 0.3 %) than in young mice (6.96 ± 1.5 %). This difference disappeared at 30ºC because the CV of the aged mice significantly increased to 6.57 ± 0.9 % (p < 0.0001) (Figure 2). Detrended fluctuation analysis (DFA), a measure of correlation within a time series, was significantly lower in the old mice at 30 C (0.81 ± 0.06) than 20ºC (1.1 ± 0.04) (p < 0.008) (Figure 3). The changes in CV and DFA suggest a restoration in complexity in the old mice at 30ºC. Aged mice also showed a significant increase in the high frequency power spectral density compared at 30ºC (175.4 ± 33.2 Hz) compared to 20ºC (20.79 ± 1.72), indicating increased parasympathetic tone at NT A (p < 0.0001) (Figure 4). Conclusion Rodents are studied in cold‐stressed conditions at LT A and increased sympathetic stimulation distorts the correct view of autonomic balance. An age‐associated decline in HRV observed at LT A was ameliorated when mice were studied at their NT A . Thus, a true elucidation of autonomic neurotransmitter modulation of cardiovascular function alterations in advanced age require mammals to be at their NT A . Support or Funding Information Funded by the National Institute of Health/National Institute on Aging Intramural Research Program. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .