Sex differences in heart rate and heart rate variability in rats: Implications for translational research

Luca Carnevali; Margherita Barbetti; Rosario Statello; DeWayne P Williams; Julian F Thayer; Andrea Sgoifo

doi:10.3389/fphys.2023.1170320

Sex differences in heart rate and heart rate variability in rats: Implications for translational research

Front Physiol. 2023 Mar 24:14:1170320. doi: 10.3389/fphys.2023.1170320. eCollection 2023.

Authors

Luca Carnevali¹, Margherita Barbetti¹, Rosario Statello^{2

3}, DeWayne P Williams⁴, Julian F Thayer⁴, Andrea Sgoifo¹

Affiliations

¹ Stress Physiology Lab, Department of Chemistry, Life Sciences and Environmental Sustainability, University of Parma, Parma, Italy.
² Department of Medicine and Surgery, University of Parma, Parma, Italy.
³ Department of Medical Sciences and Public Health, University of Cagliari, Cagliari, Italy.
⁴ Department of Psychological Science, University of California, Irvine, Irvine, United States.

Abstract

The present study aimed to investigate sex differences in measures of cardiac chronotropy and heart rate variability (HRV) in 132 young adult wild-type Groningen rats (n = 45 females). Electrocardiographic signals were recorded for 48 h in freely moving rats to quantify heart rate (HR) and inter-beat interval (IBI) as measures of cardiac chronotropy, and time- and frequency-domain HRV parameters as physiological readouts of cardiac vagal modulation. Females showed greater vagally-mediated HRV despite having higher HR and shorter IBI than males during undisturbed conditions. Such differences were evident i) at any given level of HRV, and ii) both during the 12-h light/inactive and 12-h dark/active phase of the daily cycle. These findings replicate the paradoxical cardiac chronotropic control reported by human meta-analytic findings, since one would expect greater vagally-mediated HRV to be associated with lower HR and longer IBI. Lastly, the association between some HRV measures and HR was stronger in female than male rats. Overall, the current study in young adult rats provides data illustrating a sex-dependent association between vagally-mediated HRV and indexes of cardiac chronotropy. The current results i) are in line with human findings, ii) suggest to always consider biological sex in the analysis and interpretation of HRV data in rats, and iii) warrant the use of rats for investigating the neuro-hormonal basis and temporal evolution of the impact of sex on the association between vagally-mediated HRV and cardiac chronotropy, which could inform the human condition.

Keywords: heart rate; heart rate variabiity (HRV); rats; sex differences; vagal.

Grants and funding

Funder: Project funded under the National Recovery and Resilience Plan (NRRP), Mission 4 Component 2 Investment 1.3—Call for tender No. 341 of 15/03/2022 of Italian Ministry of University and Research funded by the European Union–NextGenerationEU. Award Number: Project code PE0000006, Concession Decree No. 1553 of 11/10/2022 adopted by the Italian Ministry of University and Research, CUP D93C22000930002, “A multiscale integrated approach to the study of the nervous system in health and disease” (MNESYS).