Bone mechanical loading reduces heart rate and increases heart rate variability in mice

Figures

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  Fig. 1. Heart rate and HRV during and after bone loading in adult mice. A) (Top) Photograph of the in vivo bone loading setup showing animal positioning, direction of loading of the tibia and placement of ECG and body temperature recording leads. (Bottom) Representative ECG signal from an adult mouse showing interval measurements. B) Tachograms of resting heart rate derived from ECG signals in anesthetized 5–6 month old control mice and in mice during the tibia mechanical loading protocol. C) Average male resting heart rate and standard deviation of the RR interval (SDRR) relative to baseline during mechanical loading and during 15 min after loading in 5–6 month old mice. D) Average female resting heart rate and standard deviation of the RR interval (SDRR) relative to baseline during mechanical loading and during 15 min after loading in 5–6 month old mice. **p < 0.01 vs. control, Mixed Model ANOVA with Bonferroni post hoc analysis, n = 6–7 mice per group.

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  Fig. 2. ECG intervals during and after bone loading in adult mice. Male PR interval (A), QRS interval (B), and corrected QT interval (QTc) (C) relative to baseline during mechanical loading and during 15 min after loading in 5–6 month old mice. Female PR interval (D), QRS interval (E), and corrected QT interval (QTc) (F) relative to baseline during mechanical loading and during 15 min after loading in 5–6 month old mice. Outlier data points are denoted as an X. Mixed Model ANOVA with Bonferroni post hoc analysis, n = 6–7 mice per group.

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  Fig. 3. Effect of various magnitudes of bone load on heart rate and bone strain in adult mice. Average change in heart rate (A) and standard deviation of the RR interval (SDRR) (B) in response to tibia mechanical loading at 1–9 N in 2–6 month old male mice. Outlier data points are denoted as an X. **p < 0.01, *p < 0.05, one-way ANOVA with Bonferroni post hoc analysis, n = 7–13 mice per group. C) Strain gauge measurements in isolated tibia from adult 6 month old mice during mechanical loading at 3–9 N. Fitted line determined by simple linear regression, n = 3 mice.

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  Fig. 4. Heart rate and HRV during and after bone loading in middle-age mice. A) Tachograms of resting heart rate derived from ECG signals in 11–12 month old, anesthetized control mice and in mice during the tibia mechanical loading protocol at 3 N and 9 N. B) Average male resting heart rate and C) standard deviation of the RR interval (SDRR) relative to baseline during mechanical loading at 3 N and during 15 min after loading in 11–12 month old mice. D) Average male resting heart rate and E) standard deviation of the RR interval (SDRR) relative to baseline during mechanical loading at 9 N and during 15 min after loading in 11–12 month old mice. Mixed Model ANOVA with Bonferroni post hoc analysis, n = 7–13 mice per group. F) Average resting heart rate as beats per minute (BPM) and (G) heart rate variability as SDRR in adult and middle age male mice during anesthetized ECG. *p < 0.05, two-tailed t-test, n = 26–27 mice per group. Outlier data points are denoted as an X.

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  Fig. 5. ECG intervals during and after bone loading in middle-age mice. Male PR interval (A), QRS interval (B), and corrected QT interval (QTc) (C) relative to baseline during mechanical loading and during 15 min after loading in 11–12 month old mice. Female PR interval (D), QRS interval (E), and corrected QT interval (QTc) (F) relative to baseline during mechanical loading and during 15 min after loading in 11–12 month old mice. Outlier data points are denoted as an X. Mixed Model ANOVA with Bonferroni post hoc analysis, n = 7–13 mice per group.

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  Fig. 6. Effect of neural blockade on heart rate during bone loading in adult mice. Representative tachograms showing heart rate (Top), average changes in heart rate relative to baseline (Middle), and average changes to RR interval (Bottom) in response to mechanical loading in mice pre-treated with lidocaine injected in the hindlimb (A), atropine injected IP (B), and propranolol injected IP (C). Outlier data points are denoted as an X. **p < 0.01, *p < 0.05, two-tailed t-test, n = 7–11 mice per group.

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  Supplemental Fig. 1. Effect of lidocaine on heart rate before bone loading in adult mice. A) Representative tachograms showing heart rate in response to vehicle and lidocaine injection in the hindlimb prior to mechanical loading in mice. B) Average changes in heart rate relative to baseline five minutes after vehicle or lidocaine injection and just prior to bone mechanical loading. Two-tailed t-test, n = 7–8 mice per group.