Ivabradine increases the high frequency gain ratio in the vagal heart rate transfer function via an interaction with muscarinic potassium channels

Adaptation to head-down-tilt bed rest leads to an apparent abnormality of baroreflex regulation of cardiac period. We hypothesized that this “deconditioning response” could primarily be a result of hypovolemia, rather than a unique adaptation of the autonomic nervous system to bed rest. To test this hypothesis, nine healthy subjects underwent 2 wk of −6° head-down bed rest. One year later, five of these same subjects underwent acute hypovolemia with furosemide to produce the same reductions in plasma volume observed after bed rest. We took advantage of power spectral and transfer function analysis to examine the dynamic relationship between blood pressure (BP) and R-R interval. We found that 1) there were no significant differences between these two interventions with respect to changes in numerous cardiovascular indices, including cardiac filling pressures, arterial pressure, cardiac output, or stroke volume; 2) normalized high-frequency (0.15–0.25 Hz) power of R-R interval variability decreased significantly after both conditions, consistent with similar degrees of vagal withdrawal; 3) transfer function gain (BP to R-R interval), used as an index of arterial-cardiac baroreflex sensitivity, decreased significantly to a similar extent after both conditions in the high-frequency range; the gain also decreased similarly when expressed as BP to heart rate × stroke volume, which provides an index of the ability of the baroreflex to alter BP by modifying systemic flow; and 4) however, the low-frequency (0.05–0.15 Hz) power of systolic BP variability decreased after bed rest (−22%) compared with an increase (+155%) after acute hypovolemia, suggesting a differential response for the regulation of vascular resistance (interaction, P < 0.05). The similarity of changes in the reflex control of the circulation under both conditions is consistent with the hypothesis that reductions in plasma volume may be largely responsible for the observed changes in cardiac baroreflex control after bed rest. However, changes in vasomotor function associated with these two conditions may be different and may suggest a cardiovascular remodeling after bed rest.

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Effects of whole body heating on dynamic baroreflex regulation of heart rate in humans

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.2000.279.5.h2486 ◽

2000 ◽

Vol 279 (5) ◽

pp. H2486-H2492 ◽

Cited By ~ 38

Author(s):

C. G. Crandall ◽

R. Zhang ◽

B. D. Levine

Keyword(s):

Blood Pressure ◽

Heart Rate ◽

Heat Stress ◽

Transfer Function ◽

High Frequency ◽

Low Frequency ◽

Whole Body ◽

High Frequency Range ◽

Frequency Range ◽

Transfer Function Analysis

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0.25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2–0.3 Hz), reduced SBP variability within the low-frequency range (0.03–0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 ± 0.06 to 0.54 ± 0.6 beats · min−1 · mmHg−1; P < 0.001) without significantly affecting the gain in the low-frequency range ( P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.

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Effect of Hypoglycemia on Heart Rate Variability in People with Type 1 Diabetes and Impaired Awareness of Hypoglycemia

Journal of Diabetes Science and Technology ◽

10.1177/19322968211007485 ◽

2021 ◽

pp. 193229682110074

Author(s):

Mats Koeneman ◽

Marleen Olde Bekkink ◽

Lian van Meijel ◽

Sebastian Bredie ◽

Bastiaan de Galan

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

High Frequency ◽

Sympathetic Activity ◽

Elevated Risk ◽

Wilcoxon Rank Sum Test ◽

Impaired Awareness ◽

Induced Changes ◽

Measurable Change

Background: People with impaired awareness of hypoglycemia (IAH) are at elevated risk of severe, potentially hazardous, hypoglycemia and would benefit from a device alerting to hypoglycemia. Heart rate variability (HRV) changes with hypoglycemia due to sympathetic activity. Since IAH is associated with suppressed sympathetic activity, we investigated whether hypoglycemia elicits a measurable change in HRV in patients with T1D and IAH. Method: Eligible participants underwent a modified hyperinsulinemic euglycemic hypoglycemic clamp (glucose nadir, 43.1 ± 0.90 mg/dl), while HRV was measured by a VitalConnect HealthPatch. Measurements of HRV included Root Mean Square of the Successive Differences (RMSSD) and low to high frequency (LF:HF) ratio. Wilcoxon rank-sum test was used for testing within-subject HRV changes. Results: We included 12 participants (8 female, mean age 57 ± 12 years, mean HbA1c 57 ± 5 mmol/mol (7.4 ± 0.4%)). Symptoms increased from 4.0 (1.5-7.0) at euglycemia to 7.5 (5.0-11.0) during hypoglycemia ( P = .003). In response to hypoglycemia, the LF:HF ratio and RMSSD increased when normalized for data obtained during euglycemia (both P < .01). The LF:HF ratio increased in 6 participants (50%) and declined in one other participant (8%). The RMSSD decreased in 3 (25%) and increased in 4 (33%) participants. In 2 patients, no change in HRV could be detected in response to hypoglycemia. Conclusions: This study reveals that hypoglycemia-induced changes in HRV are retained in the majority of people with T1D and IAH, and that these changes can be detected by a wearable device. Real-time HRV seems usable for detection of hypoglycemia in patients with IAH.

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Effect of short-term exposure to particulate air pollution on heart rate variability in normal-weight and obese adults

Environmental Health ◽

10.1186/s12940-021-00707-0 ◽

2021 ◽

Vol 20 (1) ◽

Author(s):

Luyi Li ◽

Dayu Hu ◽

Wenlou Zhang ◽

Liyan Cui ◽

Xu Jia ◽

...

Keyword(s):

Heart Rate ◽

Air Pollution ◽

Heart Rate Variability ◽

High Frequency ◽

Normal Weight ◽

High Frequency Power ◽

Short Term ◽

Particulate Air Pollution ◽

Short Term Exposure ◽

Frequency Power

Abstract Background The adverse effects of particulate air pollution on heart rate variability (HRV) have been reported. However, it remains unclear whether they differ by the weight status as well as between wake and sleep. Methods A repeated-measure study was conducted in 97 young adults in Beijing, China, and they were classified by body mass index (BMI) as normal-weight (BMI, 18.5–24.0 kg/m2) and obese (BMI ≥ 28.0 kg/m2) groups. Personal exposures to fine particulate matter (PM2.5) and black carbon (BC) were measured with portable exposure monitors, and the ambient PM2.5/BC concentrations were obtained from the fixed monitoring sites near the subjects’ residences. HRV and heart rate (HR) were monitored by 24-h Holter electrocardiography. The study period was divided into waking and sleeping hours according to time-activity diaries. Linear mixed-effects models were used to investigate the effects of PM2.5/BC on HRV and HR in both groups during wake and sleep. Results The effects of short-term exposure to PM2.5/BC on HRV were more pronounced among obese participants. In the normal-weight group, the positive association between personal PM2.5/BC exposure and high-frequency power (HF) as well as the ratio of low-frequency power to high-frequency power (LF/HF) was observed during wakefulness. In the obese group, personal PM2.5/BC exposure was negatively associated with HF but positively associated with LF/HF during wakefulness, whereas it was negatively correlated to total power and standard deviation of all NN intervals (SDNN) during sleep. An interquartile range (IQR) increase in BC at 2-h moving average was associated with 37.64% (95% confidence interval [CI]: 25.03, 51.51%) increases in LF/HF during wakefulness and associated with 6.28% (95% CI: − 17.26, 6.15%) decreases in SDNN during sleep in obese individuals, and the interaction terms between BC and obesity in LF/HF and SDNN were both statistically significant (p < 0.05). The results also suggested that the effects of PM2.5/BC exposure on several HRV indices and HR differed in magnitude or direction between wake and sleep. Conclusions Short-term exposure to PM2.5/BC is associated with HRV and HR, especially in obese individuals. The circadian rhythm of HRV should be considered in future studies when HRV is applied. Graphical abstract

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Heart rate variability and baroreflex sensitivity are reduced in chronically undernourished, but otherwise healthy, human subjects

Clinical Science ◽

10.1042/cs1040295 ◽

2003 ◽

Vol 104 (3) ◽

pp. 295-302 ◽

Cited By ~ 4

Author(s):

Mario VAZ ◽

A.V. BHARATHI ◽

S. SUCHARITA ◽

D. NAZARETH

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

High Frequency ◽

Baroreflex Sensitivity ◽

Human Subjects ◽

Normal Weight ◽

Autonomic Nerve ◽

Total Power ◽

Healthy Human ◽

Frequency Power

Alterations in autonomic nerve activity in subjects in a chronically undernourished state have been proposed, but have been inadequately documented. The present study evaluated heart rate and systolic blood pressure variability in the frequency domain in two underweight groups, one of which was undernourished and recruited from the lower socio-economic strata [underweight, undernourished (UW/UN); n = 15], while the other was from a high class of socio-economic background [underweight, well nourished (UW/WN); n = 17], as well as in normal-weight controls [normal weight, well nourished (NW/WN); n = 27]. Baroreflex sensitivity, which is a determinant of heart rate variability, was also assessed. The data indicate that total power (0–0.4Hz), low-frequency power (0.04–0.15Hz) and high-frequency power (0.15–0.4Hz) of RR interval variability were significantly lower in the UW/UN subjects (P<0.05) than in the NW/WN controls when expressed in absolute units, but not when the low- and high-frequency components were normalized for total power. Baroreflex sensitivity was similarly lower in the UW/UN group (P<0.05). Heart rate variability parameters in the UW/WN group were generally between those of the UW/UN and NW/WN groups, but were not statistically different from either. The mechanisms that contribute to the observed differences between undernourished and normal-weight groups, and the implications of these differences, remain to be elucidated.

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Frequency modulation between low- and high-frequency components of the heart rate variability spectrum

Biomedical Engineering / Biomedizinische Technik ◽

10.1515/bmt.2006.049 ◽

2006 ◽

Vol 51 (4) ◽

pp. 251-254 ◽

Cited By ~ 1

Author(s):

Yuru Zhong ◽

Kung-Ming Jan ◽

Ki H. Chon

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Frequency Modulation ◽

High Frequency ◽

Frequency Components ◽

Heart Rate Variability Spectrum

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Increased high-frequency heart rate variability during insulin-induced hypoglycaemia in healthy humans

Clinical Science ◽

10.1042/cs20030337 ◽

2004 ◽

Vol 106 (6) ◽

pp. 583-588 ◽

Cited By ~ 21

Author(s):

Hartmut SCHÄCHINGER ◽

Johannes PORT ◽

Stuart BRODY ◽

Lilly LINDER ◽

Frank H. WILHELM ◽

...

Keyword(s):

Heart Rate ◽

High Frequency ◽

Concomitant Increase ◽

Plasma Adrenaline ◽

Non Invasive ◽

Hyperinsulinaemic Clamp ◽

Healthy Humans ◽

Plasma Insulin Levels ◽

Single Blind ◽

Cardiac Autonomic Activity

Despite causing sympathetic activation, prolonged hypoglycaemia produces little change in HR (heart rate) in healthy young adults. One explanation could be concurrent parasympathetic activation, resulting in unchanged net effects of autonomic influences. In the present study, hypoglycaemic (2.7 mmol/l) and normoglycaemic (4.7 mmol/l) hyperinsulinaemic clamp studies were performed after normoglycaemic baseline clamp periods with 15 healthy volunteers (seven male; mean age, 27 years) on two occasions in a randomized single-blind cross-over design. Non-invasive indices of cardiac autonomic activity and hormones were measured at baseline and 1 h after the beginning of hypoglycaemia or control normoglycaemia. Plasma insulin levels and mean HR were similar during both conditions. During hypoglycaemia, there was a 485% increase in plasma adrenaline (epinephrine). A shortening of the pre-ejection period by 45% suggested strong sympathetic cardiac activation. High-frequency (0.15–0.45 Hz) HRV (HR variability) increased, indicating a concomitant increase in parasympathetic tone. Thus, during hypoglycaemia-induced sympathetic cardiac activation in healthy adults, parasympathetic mechanisms are involved in stabilizing mean HR.

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The Influence ofNrf2on Cardiac Responses to Environmental Stressors

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/901239 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 1

Author(s):

Reuben Howden ◽

Eva Gougian ◽

Marcus Lawrence ◽

Samantha Cividanes ◽

Wesley Gladwell ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

High Frequency ◽

Low Frequency ◽

Therapeutic Strategies ◽

Environmental Stressors ◽

Total Power ◽

Airborne Pollutants ◽

Cardiac Responses

Nrf2protects the lung from adverse responses to oxidants, including 100% oxygen (hyperoxia) and airborne pollutants like particulate matter (PM) exposure, but the role ofNrf2on heart rate (HR) and heart rate variability (HRV) responses is not known. We hypothesized that genetic disruption ofNrf2would exacerbate murine HR and HRV responses to severe hyperoxia or moderate PM exposures.Nrf2-/-andNrf2+/+mice were instrumented for continuous ECG recording to calculate HR and HRV (low frequency (LF), high frequency (HF), and total power (TP)). Mice were then either exposed to hyperoxia for up to 72 hrs or aspirated with ultrafine PM (UF-PM). Compared to respective controls, UF-PM induced significantly greater effects on HR (P<0.001) and HF HRV (P<0.001) inNrf2-/-mice compared toNrf2+/+mice.Nrf2-/-mice tolerated hyperoxia significantly less thanNrf2+/+mice (~22 hrs;P<0.001). Reductions in HR, LF, HF, and TP HRV were also significantly greater inNrf2-/-compared toNrf2+/+mice (P<0.01). Results demonstrate thatNrf2deletion increases susceptibility to change in HR and HRV responses to environmental stressors and suggest potential therapeutic strategies to prevent cardiovascular alterations.

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Effect of Acupuncture on Heart Rate Variability: A Systematic Review

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2014/819871 ◽

2014 ◽

Vol 2014 ◽

pp. 1-19 ◽

Cited By ~ 22

Author(s):

Joanne W. Y. Chung ◽

Vincent C. M. Yan ◽

Hongwei Zhang

Keyword(s):

Systematic Review ◽

Heart Rate ◽

Heart Rate Variability ◽

High Frequency ◽

Healthy Subjects ◽

Keyword Search ◽

Data Extraction ◽

Meta Analysis ◽

Low Frequency ◽

Control Group

Aim.To summarize all relevant trials and critically evaluate the effect of acupuncture on heart rate variability (HRV).Method.This was a systematic review with meta-analysis. Keyword search was conducted in 7 databases for randomized controlled trials (RCTs). Data extraction and risk of bias were done.Results.Fourteen included studies showed a decreasing effect of acupuncture on low frequency (LF) and low frequency to high frequency ratio (LF/HF ratio) of HRV for nonhealthy subjects and on normalized low frequency (LF norm) for healthy subjects. The overall effect was in favour of the sham/control group for high frequency (HF) in nonhealthy subjects and for normalized high frequency (HF norm) in healthy subjects. Significant decreasing effect on HF and LF/HF ratio of HRV when acupuncture was performed on ST36 among healthy subjects and PC6 among both healthy and nonhealthy subjects, respectively.Discussion.This study partially supports the possible effect of acupuncture in modulating the LF of HRV in both healthy and nonhealthy subjects, while previous review reported that acupuncture did not have any convincing effect on HRV in healthy subjects. More published work is needed in this area to determine if HRV can be an indicator of the therapeutic effect of acupuncture.

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Modulation of Neurocardiac Function by Oesophageal Stimulation in Humans

Clinical Science ◽

10.1042/cs0920167 ◽

1997 ◽

Vol 92 (2) ◽

pp. 167-174 ◽

Cited By ~ 42

Author(s):

Gervais Tougas ◽

Markad Kamath ◽

Geena Watteel ◽

Debbie Fitzpatrick ◽

Ernest L. Fallen ◽

...

Keyword(s):

Heart Rate ◽

Heart Rate Variability ◽

Power Spectrum ◽

High Frequency ◽

Low Frequency ◽

Sensory Stimulation ◽

Sensory Stimuli ◽

Autonomic Reflexes ◽

Low Frequency Power ◽

Beat Heart

1. The heart and the oesophagus have similar sensory pathways, and sensations originating from the oesophagus are often difficult to differentiate from those of cardiac origin. We hypothesized that oesophageal sensory stimuli could alter neurocardiac function through autonomic reflexes elicited by these oesophageal stimuli. In the present study, we examined the neurocardiac response to oesophageal stimulation and the effects of electrical and mechanical oesophageal stimulation on the power spectrum of beat-to-beat heart rate variability in male volunteers. 2. In 14 healthy volunteers, beat-to-beat heart rate variability was compared at rest and during oesophageal stimulation, using either electrical (200 μs, 16 mA, 0.2 Hz) or mechanical (0.5 s, 14 ml, 0.2 Hz) stimuli. The power spectrum of beat-to-beat heart rate variability was obtained and its low- and high-frequency components were determined. 3. Distal oesophageal stimulation decreased heart rate slightly (both electrical and mechanical) (P < 0.005), and markedly altered heart rate variability (P < 0.001). Both electrical and mechanical oesophageal stimulation increased the absolute and normalized area of the high-frequency band within the power spectrum (P < 0.001), while simultaneously decreasing the low-frequency power (P < 0.005). 4. In humans, oesophageal stimulation, whether electrical or mechanical, appears to amplify respiratory-driven cardiac vagoafferent modulation while decreasing sympathetic modulation. The technique provides access to vagoafferent fibres and thus may yield useful information on the autonomic effects of visceral or oesophageal sensory stimulation.

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