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

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.

Sex differences in heart rate variability measures that predict alcohol drinking in rats

“…Raw 10‐min recordings were visually inspected to remove artefacts and missed heartbeats, as done in other studies. 40 , 54 , 55 , 56 In addition, we note that on a technical level, shorter analysis periods increase variability, whereas longer HR traces give greater data and a more accurate HRV assessment. However, several studies find that briefer analysis windows can provide meaningful findings, and 5 min is often used for a briefer baseline for humans.…”

“…This agrees with human studies where women show higher HRV even with greater HR 36 and rodent studies replicating a similar pattern by sex. 40 , 41 …”

“…Many studies have observed baseline HR/HRV differences between men and freely cycling women, 29 , 36 , 38 which is congruent with studies in rodent. 40 , 41 However, oestrogen can enhance PNS in humans 37 , 46 and rodents, 42 although one study in humans found greater effects of sex differences on HRV than cycle stage differences. 43 Also, estrous cycle sometimes has limited influence on level of intake once rodent addictive behaviours are established.…”

“…Raw recordings were visually inspected to remove artefacts, missed heartbeats and ectopic heartbeats, as is typically done in other studies. 40 , 54 , 56 NOTOCORD‐hem software output the timing of each successive heartbeat peak. This time series was used to determine HR (beats/min) and also the sequence of IBIs (in msec) across a given session.…”

“… 39 In addition, females can display greater basal HRV than males in humans 35 , 36 , 37 , 38 and in rats. 40 , 41 In addition, several studies find sex differences in autonomic markers evident during challenge, especially those suggesting that women utilize the PNS more, whereas men engage the SNS more. 29 , 35 , 38 , 42 , 43 HRV‐related brain circuits also differ in relation to biological sex.…”