Original Article
The Impact of Remote Ischaemic Conditioning on Beat-to-Beat Heart Rate Variability Circadian Rhythm in Healthy Adults

https://doi.org/10.1016/j.hlc.2020.08.017Get rights and content

Background

Remote ischaemic conditioning (RIC) is an intervention that may exert a protective effect over multiple tissues or organs by regulating neuronal signal transduction. Heart rate variability (HRV) can assess the state of the autonomic nervous system. However, whether RIC can also regulate HRV in humans remains unknown.

Method

This was a self-controlled interventional study in which serial beat-to-beat monitoring was performed at the same seven time points (7, 9, and 11 AM; 2, 5, and 8 PM; and 8 AM on the next day) with or without RIC in 50 healthy adults. The seven time points on the RIC day were defined as baseline, 1 hour, 3 hours, 6 hours, 9 hours, 12 hours, and 24 hours after RIC. The RIC protocol consisted of 4×5-minute inflation/deflation in one arm and one thigh cuff at 200 mmHg pressure from 7:20 to 8 AM. This study is registered on ClinicalTrials.gov (NCT02965547).

Results

We included 50 healthy adult volunteers (aged 34.54±12.01 years, 22 men [44%], all Asian). The variables analysed in frequency–domain measures performed as power of low-frequency in normalised units (0.04–0.15 Hz), high-frequency in normalised units (0.15–0.40 Hz), and ratio of low frequency to high frequency. The time–domain parameters standard deviation (SD) of all normal to normal (NN) intervals (SDNN), mean of the 5-minute SD of the NN intervals, SD of the consecutive 5-minute averages of NN intervals, and the root mean square of successive differences of NN intervals, and time–domain parameters calculated from Poincaré plots, SD of the short diagonal axis in Poincaré plot (SD1), SD of the long diagonal axis in Poincaré plot (SD2), and SD1/SD2 were also obtained. The SDNN and SD2 significantly increased 1 hour after RIC (p=0.029 and p=0.045, respectively). Additionally, the SD2 increased a second time 12 hours after RIC (p=0.041), which represented inhibited sympathetic activity.

Conclusions

Heart rate variability increase and sympathetic inhibition induced by RIC appeared both on the early and delayed protective window of RIC, which may indicate some of the underlying mechanisms by which RIC may offer protection.

Introduction

Remote ischaemic conditioning (RIC) is an intervention in which small doses of reversible episodes of ischaemia and reperfusion are applied in distant tissues or organs, recruiting protective pathways and rendering remote tissues and organs resistant to ischaemia/reperfusion injury [1,2], a process first demonstrated by Murry et al. in 1986 [3]. Since then, RIC has been studied extensively. According to the available evidence, RIC exerts a potentially protective effect to multiple tissues or organs of human body at the same time, such as the heart [4,5], brain [6,7], kidney [8], lung [9], and liver [10], by activating neurogenic pathways, humoral factors, and the immune system [11]. However, the exact mechanisms of RIC are still not fully understood.

Heart rate (HR) variability (HRV) is defined as HR oscillation in relation to the mean value [12]. Many physiological and pathological processes may lead to HRV changes, such as mental or physical stress, cardiac or non-cardiac diseases, and pharmacological or invasive treatments [13]. It has been widely demonstrated that the frequency and time domain of cardiovascular rhythmicity, such as HRV, can be used to assess the state of sympathetic and parasympathetic balance [14]. Remote ischaemic conditioning regulates neuronal signal transduction to protect vital organs. Several studies have demonstrated the regulation of RIC on HRV [[15], [16], [17], [18]]; however, the RIC procedures and results are very heterogeneous, and how long the regulation exist remains unknown.

The main objective of this study was to assess the impact of RIC on HRV circadian rhythm to explore whether RIC can influence the autonomic nervous system (ANS) and how long its impact lasts. In order to avoid any confounding factors caused by the physiological circadian rhythm, we conducted a self-controlled interventional study on 4 consecutive days (control day and RIC day). The changes of time–domain indices, frequency domain parameters, and non-linear values of HRV were measured in healthy adults at seven time points (baseline and 1, 3, 6, 9, 12, and 24 hours after RIC) by beat-to-beat monitoring.

Section snippets

Participants

Fifty (50) healthy Asian adults, both males and females (age range 18–70 years) were recruited between January and July 2017. Before inclusion, each participant was subjected to a comprehensive physical examination by a physician, in order to exclude potential diseases. The exclusion criteria were (1) any infectious disease in the past month; (2) any history of chronic diseases (including hypertension, diabetes mellitus, generalised anxiety disorder, depression, insomnia, and chronic heart

Subject Characteristics

Fifty (50) healthy adult volunteers (mean age 34.54±12.01 years, 22 men [44%], all Asian) were enrolled in this study. The clinical characteristics of the participants are shown in Table 2.

RIC and HRV Circadian Rhythm

Heart rate variability circadian rhythms are presented as different time points during the daytime in Figure 2. A summary of the repeated measurements for the different parameters of HRV across the intervention (RIC) and time points is displayed in Table 3. Comparison of parameters that were significant in

Discussion

In the present study, we showed that HRV, an indication of autonomic nerve activity, was altered by RIC, which was validated in two time windows; specifically, the SDNN and SD2 increased starting within 1 hour but no more than 3 hours after RIC. The SD2 then increased for a second time at 12 hours after RIC.

To the best of our knowledge, this study is the first to evaluate the impact of RIC on HRV circadian rhythm and how long that impact will last. Several previous studies have investigated the

Conclusion

Our results suggest that RIC increases the SD2 components of HRV 1 hour and 12 hours later, indicating that ANS activity changes induced by RIC exists in both early and delayed protective windows, which may indicate some of the underlying mechanisms by which RIC offers protection. As decreased HRV has been identified to be associated with a high risk of cardiovascular death, as a therapeutic target, RIC may favourably influence the prognosis of cardiovascular diseases by ameliorating autonomic

Funding Sources

This project was supported by the National Key R&D Program of China (2016YFC1301600), JLUSTIRT (2017TD-12) and Jilin Provincial Key Laboratory (20190901005JC) to Yi Yang.

Conflicts of Interest

There are no conflicts of interest to disclose.

Author Contributions

All authors provided critical review, edits and approval of the final manuscript. Z-NG and YY devised the study design and supervised study procedures. YQ, JL, P-DZ, X-LY, and SQ conducted the experiments, analysed data, and provided results. PZ provided significant statistical support.

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