Terry B.J. Kuo

Effect of aging on gender differences in neural control of heart rate

To clarify the influence of gender on sympathetic and parasympathetic control of heart rate in middle-aged subjects and on the subsequent aging process, heart rate variability (HRV) was studied in normal populations of women ( n = 598) and men ( n = 472) ranging in age from 40 to 79 yr. These groups were divided into eight age strata at 5-yr intervals and were clinically diagnosed as having no hypertension, hypotension, diabetic neuropathy, or cardiac arrhythmia. Frequency-domain analysis of short-term, stationary R-R intervals was performed, which reveals very-low-frequency power (VLF; 0.003-0.04 Hz), low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF and HF power in normalized units (LF% and HF%, respectively). The distribution of variance, VLF, LF, HF, and LF/HF exhibited acute skewness, which was adjusted by natural logarithmic transformation. Women had higher HF in the age strata from 40 to 49 yr, whereas men had higher LF% and LF/HF between 40 and 59 yr. No disparity in HRV measurements was found between the sexes in age strata ≥60 yr. Although absolute measurements of HRV (variance, VLF, LF, and HF) decreased linearly with age, no significant change in relative measurements (LF/HF, LF%, and HF%), especially in men, was detected until age 60 yr. We conclude that middle-aged women and men have a more dominant parasympathetic and sympathetic regulation of heart rate, respectively. The gender-related difference in parasympathetic regulation diminishes after age 50 yr, whereas a significant time delay for the disappearance of sympathetic dominance occurs in men.To clarify the influence of gender on sympathetic and parasympathetic control of heart rate in middle-aged subjects and on the subsequent aging process, heart rate variability (HRV) was studied in normal populations of women (n = 598) and men (n = 472) ranging in age from 40 to 79 yr. These groups were divided into eight age strata at 5-yr intervals and were clinically diagnosed as having no hypertension, hypotension, diabetic neuropathy, or cardiac arrhythmia. Frequency-domain analysis of short-term, stationary R-R intervals was performed, which reveals very-low-frequency power (VLF; 0.003-0.04 Hz), low-frequency power (LF; 0.04-0.15 Hz), high-frequency power (HF; 0.15-0.40 Hz), the ratio of LF to HF (LF/HF), and LF and HF power in normalized units (LF% and HF%, respectively). The distribution of variance, VLF, LF, HF, and LF/HF exhibited acute skewness, which was adjusted by natural logarithmic transformation. Women had higher HF in the age strata from 40 to 49 yr, whereas men had higher LF% and LF/HF between 40 and 59 yr. No disparity in HRV measurements was found between the sexes in age strata >/=60 yr. Although absolute measurements of HRV (variance, VLF, LF, and HF) decreased linearly with age, no significant change in relative measurements (LF/HF, LF%, and HF%), especially in men, was detected until age 60 yr. We conclude that middle-aged women and men have a more dominant parasympathetic and sympathetic regulation of heart rate, respectively. The gender-related difference in parasympathetic regulation diminishes after age 50 yr, whereas a significant time delay for the disappearance of sympathetic dominance occurs in men.

Spectral analysis of systemic arterial pressure and heart rate signals as a prognostic tool for the prediction of patient outcome in the intensive care unit

OBJECTIVES To evaluate the applicability of changes in spectra of systemic arterial pressure and heart rate signals in the prediction of patient outcome in an adult intensive care unit (ICU). To compare the prognostic predictability of this method with the Acute Physiology and Chronic Health Evaluation II (APACHE II) scoring system. DESIGN Prospective data collection from 52 ICU patients. SETTING Adult ICU at a large, university-affiliated, medical center. PATIENTS Consecutive patients who were admitted to the adult ICU due to noncardiac emergencies, and who remained for at least 2 days. INTERVENTIONS None. MEASUREMENTS AND MAIN RESULTS The demographic data, diagnosis, and survival data were recorded for each patient enrolled in this study. For the period between admission and 24 hrs before discharge, the APACHE II score was tabulated daily. Likewise, continuous, on-line, and real-time spectral analysis of systemic arterial pressure and heart rate signals was carried out every day for at least 30 mins at 2200 to 2400 hrs. The averaged power density values during this 30-min recording period of the high-frequency (0.15 to 0.4 Hz), low-frequency (0.08 to 0.15 Hz), and very low-frequency (0.016 to 0.08 Hz) components of systemic arterial pressure and heart rate signals were subsequently computed. Systemic vascular resistance index and cardiac index were also determined daily. We observed a trend of changes in the spectral components of systemic arterial pressure and heart rate signals in patients who eventually survived (n = 25) or died (n = 27). Progressive increases in the power density values of both the low-frequency and very low-frequency components of systemic arterial pressure and heart rate signals appeared to be related to recovery. Conversely, progressive decreases in the power density values of these spectral components was indicative of deterioration and fatality. The predicted outcome based on the trend of changes in the low-frequency and very low-frequency components of systemic arterial pressure and heart rate signals correlated positively with daily APACHE II scores. No direct correlation, however, was indicated by mean systemic arterial pressure, heart rate, systemic vascular resistance index, and cardiac index. We also confirmed that the differential trend of spectral changes in patients who survived or died was not due to circadian rhythm, nor alterations in the responsiveness of the blood vessels to intravenous infusion of dopamine. CONCLUSION Power spectral analysis of systemic arterial pressure and heart rate signals offers a reasonable means of monitoring acute, critically ill patients, and may be used as an alternative prognostic tool for the prediction of patient outcome in the ICU.

Frequency Domain Analysis of Cerebral Blood Flow Velocity and its Correlation with Arterial Blood Pressure

We applied frequency domain analysis to detect and quantify spontaneous fluctuations in the blood flow velocity of the middle cerebral artery (MCAFV). Instantaneous MCAFV of normal volunteers was detected using transcranial Doppler sonography. Spectral and transfer function analyses of MCAFV and arterial blood pressure (ABP) were performed by fast Fourier transform. We found the fluctuations in MCAFV, like ABP, could be diffracted into three components at specific frequency ranges, designated as high-frequency (HF, 0.15 to 0.4 Hz), low-frequency (LF, 0.04 to 0.15 Hz), and very low-frequency (VLF, 0.016 to 0.04 Hz) components. The HF and LF components of MCAFV exhibited high coherence with those of ABP, indicating great similarity of MCAFV and ABP fluctuations within the two frequency ranges. However, it was not the case for the VLF component. Transfer function analysis revealed that the ABP-MCAFV phase angle was frequency-dependent in the LF range (r = −0.79, P < 0.001) but not in the HF range. The time delay between LF fluctuations of ABP and those of MCAFV was evaluated as 2.1 seconds. We conclude that in addition to traditional B-wave equivalents, there are at least two different mechanisms for MCAFV fluctuations: the HF and LF fluctuations of MCAFV are basically secondary to those of ABP, and cerebral autoregulation may operate efficiently in LF rather than HF range. Frequency domain analysis offers an opportunity to explore the nature and underlying mechanism of dynamic regulation in cerebral circulation.

Transfer Function Analysis of Cerebral Hemodynamics in Patients With Carotid Stenosis

This study evaluates the validity of the transfer function analysis of spontaneous fluctuations of arterial blood pressure (ABP) and blood flow velocity of the middle cerebral artery (MCAFV) as a simple, convenient method to assess human cerebral autoregulation in patients with carotid stenosis. Eighty-three consecutive patients with various degrees of carotid stenosis and 37 healthy controls were enrolled. The carotid stenosis was graded based on the diagnostic criteria of duplex ultrasound. Instantaneous bilateral MCAFV and ABP of all participants were assessed noninvasively using transcranial Doppler sonography and the servocontrolled infrared finger plethysmography, respectively. Spectral analyses of ABP and MCAFV were performed by fast Fourier transform. The fluctuations in ABP as well as in MCAFV were diffracted into three components at specific frequency ranges designated as high-frequency (HF; 0.15 to 0.4 Hz), low-frequency (LF; 0.04 to 0.15 Hz), and very low-frequency (VLF; 0.016 to 0.04 Hz). Cross-spectral analysis was applied to quantify the coherence, transfer phase, and magnitude in individual HF, LF, and VLF components. Transcranial Doppler CO2 vasomotor reactivity was measured with 5% CO2 inhalation. The LF phase angle (r = −0.53, P < 0.001); magnitude of VLF (r = −0.29, P = 0.002), LF (r = −0.35, P < 0.001), and HF (r = −0.47, P < 0.001); and CO2 vasomotor reactivity (r = −0.66, P < 0.001) were negatively correlated with the severity of stenosis. Patients with unilateral high-grade (greater than 90% stenosis) carotid stenosis demonstrated significant reduction in LF phase angle (P < 0.001) and HF magnitude (P = 0.018) on the ipsilateral side of the affected vessel compared with their contralateral side. The study also revealed a high sensitivity, specificity, and accuracy using LF phase angle and HF magnitude to detect a high-grade carotid stenosis. A strong correlation existed between the LF phase angle and the CO2 vasomotor reactivity test (r = 0.62, P < 0.001), and the correlation between the HF magnitude and the CO2 vasomotor reactivity (r = 0.44, P < 0.001) was statistically significant as well. We conclude that transfer function analysis of spontaneous fluctuations of MCAFV and ABP could be used to identify hemodynamically significant high-grade carotid stenosis with impaired cerebral autoregulation or vasomotor reserve.

Relationship between electroencephalogram slow-wave magnitude and heart rate variability during sleep in humans

To explore whether depth of sleep is related to changes in autonomic control, continuous power-spectral analysis of the electroencephalogram (EEG) and heart rate variability (HRV) was performed in ten normal subjects during nocturnal sleep. Quiet sleep (QS) was associated with an increase in high-frequency power (HF) of HRV (0.15-0.4 Hz) but a decrease in low-frequency power (LF) (0.04-0.15 Hz) to HF ratio (LF/HF) compared with awakening. During QS, LF/HF was significantly and negatively correlated with delta power of EEG (0.5-4.0 Hz), whereas mean R-R interval and HF were not. We conclude that during QS, cardiac sympathetic regulation is negatively related to the depth of sleep, although vagal regulation is not. Our methodology offers a quantitative analysis to study the interaction between cerebral cortical and autonomic functions.

An alternative method to enhance vagal activities and suppress sympathetic activities in humans

Vagal withdrawal and/or sympathetic overactivity is always accompanied by various kinds of stress and is dangerous to the body. We proposed that mild acupuncture on the Sishencong points may effectively enhance vagal activities but suppress sympathetic regulations of the heart in humans. Experiments were carried out on nine healthy male volunteers, while they were lying in a quiet room during 2-4 P.M. Acupuncture was applied 2 mm deep into the skin using standard stainless acupuncture needles at the Sishencong points, which are located on the vertex of the head, each 1 cm away from Baihui (GV 20) in four directions. Four points around the temporal area were selected as control points. Forty minutes of precordial ECG signals before, during, and after acupuncture were recorded continuously. Frequency-domain analysis of the stationary RR intervals was performed to evaluate the total variance, high-frequency power (HF, 0.15-0.40 Hz) and low-frequency power (LF, 0.04-0.15 Hz) in normalized units (LF%). Acupuncture on the Sishencong points resulted in an increased HF but a decreased LF% compared with the before acupuncture stage. Such effects did not occur when manual acupuncture was applied to the control points. The differences in the heart rate dynamics between Sishencong and the control groups took place 10 min after initiation of acupuncture and persisted even after the removal of the needles. Based on these results, we concluded that manual acupuncture on the Sishencong points enhanced cardiac vagal and suppressed sympathetic activities in humans. The underlying mechanisms and potential applications warrant further investigations.

Development and Validation of the Smartphone Addiction Inventory (SPAI)

Objective The aim of this study was to develop a self-administered scale based on the special features of smartphone. The reliability and validity of the Smartphone Addiction Inventory (SPAI) was demonstrated. Methods A total of 283 participants were recruited from Dec. 2012 to Jul. 2013 to complete a set of questionnaires, including a 26-item SPAI modified from the Chinese Internet Addiction Scale and phantom vibration and ringing syndrome questionnaire. There were 260 males and 23 females, with ages 22.9±2.0 years. Exploratory factor analysis, internal-consistency test, test-retest, and correlation analysis were conducted to verify the reliability and validity of the SPAI. Correlations between each subscale and phantom vibration and ringing were also explored. Results Exploratory factor analysis yielded four factors: compulsive behavior, functional impairment, withdrawal and tolerance. Test–retest reliabilities (intraclass correlations  = 0.74–0.91) and internal consistency (Cronbachs α = 0.94) were all satisfactory. The four subscales had moderate to high correlations (0.56–0.78), but had no or very low correlation to phantom vibration/ringing syndrome. Conclusion This study provides evidence that the SPAI is a valid and reliable, self-administered screening tool to investigate smartphone addiction. Phantom vibration and ringing might be independent entities of smartphone addiction.

Regression Analysis Between Heart Rate Variability and Baroreflex-Related Vagus Nerve Activity in Rats

Introduction: Many previous studies have suggested that the high‐frequency (HF) power of the heart rate variability may represent cardiac vagal activity although direct evidence of a correlation between the HF and vagal neuronal activity is still lacking. In the present study, we performed a regression analysis of the HF and vagal neurograms.

Sleep-Related Changes in Cardiovascular Neural Regulation in Spontaneously Hypertensive Rats

Background—Sleep has significant effects on cardiovascular neural regulation. The aim of this study is to explore the possible change in sympathetic vasomotor activity and baroreflex sensitivity associated with spontaneous hypertension during each stage of the sleep-wake cycle. Methods and Results—Polysomnographic analysis was performed in freely moving spontaneously hypertensive rats (SHR) and normotensive Wistar-Kyoto rats (WKY) during their normal daytime sleep. Continuous spectral analyses of electroencephalogram and electromyogram were performed to define active waking, quiet sleep, and paradoxical sleep. Low-frequency power of the arterial pressure variability (BLF) was quantified to provide an index of sympathetic vasomotor activity. Spontaneous baroreflex sensitivity was assessed (1) by the slopes of the regression lines of the mean arterial pressure and R-R intervals pairs that ascended (BrrA) or descended (BrrD) successively and (2) by the magnitudes of the arterial pressure and R-R intervals transfer functions in the high-frequency (BrrHF) or low-frequency (BrrLF) ranges. SHR had significantly higher mean arterial pressure during each of the sleep-wake states. Although the values of BLF, BrrA, BrrD, BrrHF, and BrrLF in SHR did not differ from those of WKY during active waking, SHR had a significantly higher BLF and lower BrrA, BrrD, BrrHF, and BrrLF compared with WKY during quiet sleep and paradoxical sleep. Conclusions—SHR had enhanced sympathetic vasomotor activity but attenuated baroreflex sensitivity during sleep although each phenomenon was not evident when awake.

Pre-operative measurement of heart rate variability predicts hypotension during general anesthesia

Background:  Peri‐operative hymodynamic instability is one of the major concerns for anesthesiologists when performing general anesthesia for individuals with autonomic dysfunction. The purpose of this study was to examine the potential usage of pre‐operative measurement of heart rate variability (HRV) in identifying which individuals, with or without diabetes, may be at risk of blood pressure (BP) instability during general anesthesia.