Utility of spectrum and wavelet analysis of heart rate variability as a tool to assess orthostatic intolerance

Three studies were performed to test the hypotheses: (1) lower body negative pressure (LBNP) tolerance, autonomic, and cardiovascular responses to the LBNP are reproducible, (2) women have a lower LBNP tolerance and less ability to maintain homeostasis in cardiovascular system against orthostatic stress, and (3) wavelet analysis technique is a unique tool to study the autonomic nervous activities during LBNP test. College-age men and women underwent graded LBNP to either presyncope or -100 mmHg in increments of 10 mmHg negative pressure every 6 minutes;The LBNP tolerance were highly reproducible (cumulative stress index: 1698 +/- 171 vs 1938 +/- 139, trial 1 vs trial 2, respectively; Cronbach alpha coefficient = 0.87). Changes of the autonomic and cardiovascular responses in the two trials were similar. Autonomic and cardiovascular responses to LBNP at most level were reproducible (alpha coefficient ≥ 0.41);The females showed 44% less tolerance to the orthostatic stress induced by LBNP than the male. Heart rate increased above rest at ≥-40 mmHg (P \u3c 0.05) in both groups and mean arterial pressure was maintained in males while it fell below rest at ≥-30 mmHg (P \u3c 0.05) in females. Based on spectral analysis, sympathetic nervous system activity as quantified by the LF/HF ratio increased above rest at ≥-40 mmHg in males but it increased only at presyncope in females (P \u3c 0.05);The wavelet analysis technique is a valuable-unique tool to study autonomic responses to LBNP over spectral analysis since: (1) this method provides a dynamic autonomic response to LBNP by showing both time- and frequency-description simultaneously and (2) this method yield the additional valuable information from transient and nonstationary part of heart rate signal which normally discarded to satisfy the underlying condition of spectral analysis;These results suggest that (1) LBNP tolerance, autonomic, and cardiovascular responses to LBNP are reproducible, (2) women have a lower orthostatic tolerance than men and this gender difference in orthostatic tolerance may be due to differences in the autonomic activity responses to this stress, and (3) wavelet analysis is a unique tool over spectral analysis to access autonomic responses to LBNP

A Model for the Genesis of Arterial Pressure Mayer Waves from Heart Rate and Sympathetic Activity

Both theoretic models and cross-spectral analyses suggest that an oscillating sympathetic nervous outflow generates the low frequency arterial pressure fluctuations termed Mayer waves. Fluctuations in heart rate also have been suggested to relate closely to Mayer waves, but empiric models have not assessed the joint causative influences of hemt rate and sympathetic activity. Therefore, we constructed a model based simply upon the hemodynamic equation deriving from Ohm's Law. With this model, we determined time relations and relative contributions of heart rate and sympathetic activity to the genesis of arterial pressure Mayer waves. We assessed data from eight healthy young volunteers in the basal state and in a high sympathetic state known to produce concurrent increases in sympathetic nervous outflow and Mayer wave amplitude. We fit the Mayer waves (0.05-0.20 Hz) in mean arterial pressure by the weighted sum ofleading oscillations in heart rate and sympathetic nerve activity. This model of our data showed heart rate oscillations leading by 2-3.75 seconds were responsible for almost half of the variance in arterial pressure (basal R^2=0.435±0.140, high sympathetic R^2=0.438±0.180). Surprisingly, sympathetic activity (lead 0-5 seconds) contributed only modestly to the explained variance in Mayer waves during either sympathetic state (basal: ∆R^2=0.046±0.026; heightened: ∆R^2=0.085±0.036). Thus, it appears that heart rate oscillations contribute to Mayer waves in a simple linear fashion, whereas sympathetic fluctuations contribute little to Mayer waves in this way. Although these results do not exclude an important vascular sympathetic role, they do suggest that additional Ji1ctors, such as sympathetic transduction into vascular resistance, modulate its influence.Binda and Fred Shuman Foundation; National Institute on Aging (AG14376)

A Model for the Genesis of Arterial Pressure Mayer Waves from Heart Rate and Sympathetic Activity

Both theoretic models and cross-spectral analyses suggest that an oscillating sympathetic nervous outflow generates the low frequency arterial pressure fluctuations termed Mayer waves. Fluctuations in heart rate also have been suggested to relate closely to Mayer waves, but empiric models have not assessed the joint causative influences of hemt rate and sympathetic activity. Therefore, we constructed a model based simply upon the hemodynamic equation deriving from Ohm's Law. With this model, we determined time relations and relative contributions of heart rate and sympathetic activity to the genesis of arterial pressure Mayer waves. We assessed data from eight healthy young volunteers in the basal state and in a high sympathetic state known to produce concurrent increases in sympathetic nervous outflow and Mayer wave amplitude. We fit the Mayer waves (0.05-0.20 Hz) in mean arterial pressure by the weighted sum ofleading oscillations in heart rate and sympathetic nerve activity. This model of our data showed heart rate oscillations leading by 2-3.75 seconds were responsible for almost half of the variance in arterial pressure (basal R^2=0.435±0.140, high sympathetic R^2=0.438±0.180). Surprisingly, sympathetic activity (lead 0-5 seconds) contributed only modestly to the explained variance in Mayer waves during either sympathetic state (basal: ∆R^2=0.046±0.026; heightened: ∆R^2=0.085±0.036). Thus, it appears that heart rate oscillations contribute to Mayer waves in a simple linear fashion, whereas sympathetic fluctuations contribute little to Mayer waves in this way. Although these results do not exclude an important vascular sympathetic role, they do suggest that additional Ji1ctors, such as sympathetic transduction into vascular resistance, modulate its influence.Binda and Fred Shuman Foundation; National Institute on Aging (AG14376)

Beyond the Baroreflex: A New Measure of Autonomic Regulation Based on the Time-Frequency Assessment of Variability, Phase Coherence and Couplings

For decades the role of autonomic regulation and the baroreflex in the generation of the respiratory sinus arrhythmia (RSA) - modulation of heart rate by the frequency of breathing - has been under dispute. We hypothesized that by using autonomic blockers we can reveal which oscillations and their interactions are suppressed, elucidating their involvement in RSA as well as in cardiovascular regulation more generally. R-R intervals, end tidal CO2, finger arterial pressure, and muscle sympathetic nerve activity (MSNA) were measured simultaneously in 7 subjects during saline, atropine and propranolol infusion. The measurements were repeated during spontaneous and fixed-frequency breathing, and apnea. The power spectra, phase coherence and couplings were calculated to characterise the variability and interactions within the cardiovascular system. Atropine reduced R-R interval variability (p \u3c 0.05) in all three breathing conditions, reduced MSNA power during apnea and removed much of the significant coherence and couplings. Propranolol had smaller effect on the power of oscillations and did not change the number of significant interactions. Most notably, atropine reduced R-R interval power in the 0.145–0.6 Hz interval during apnea, which supports the hypothesis that the RSA is modulated by a mechanism other than the baroreflex. Atropine also reduced or made negative the phase shift between the systolic and diastolic pressure, indicating the cessation of baroreflex-dependent blood pressure variability. This result suggests that coherent respiratory oscillations in the blood pressure can be used for the non-invasive assessment of autonomic regulation

Trigonometric Regressive Spectral Analysis Reliably Maps Dynamic Changes in Baroreflex Sensitivity and Autonomic Tone: The Effect of Gender and Age

BACKGROUND: The assessment of baroreflex sensitivity (BRS) has emerged as prognostic tool in cardiology. Although available computer-assisted methods, measuring spontaneous fluctuations of heart rate and blood pressure in the time and frequency domain are easily applicable, they do not allow for quantification of BRS during cardiovascular adaption processes. This, however, seems an essential criterion for clinical application. We evaluated a novel algorithm based on trigonometric regression regarding its ability to map dynamic changes in BRS and autonomic tone during cardiovascular provocation in relation to gender and age. METHODOLOGY/PRINCIPAL FINDINGS: We continuously recorded systemic arterial pressure, electrocardiogram and respiration in 23 young subjects (25+/-2 years) and 22 middle-aged subjects (56+/-4 years) during cardiovascular autonomic testing (metronomic breathing, Valsalva manoeuvre, head-up tilt). Baroreflex- and spectral analysis was performed using the algorithm of trigonometric regressive spectral analysis. There was an age-related decline in spontaneous BRS and high frequency oscillations of RR intervals. Changes in autonomic tone evoked by cardiovascular provocation were observed as shifts in the ratio of low to high frequency oscillations of RR intervals and blood pressure. Respiration at 0.1 Hz elicited an increase in BRS while head-up tilt and Valsalva manoeuvre resulted in a downregulation of BRS. The extent of autonomic adaption was in general more pronounced in young individuals and declined stronger with age in women than in men. CONCLUSIONS/SIGNIFICANCE: The trigonometric regressive spectral analysis reliably maps age- and gender-related differences in baroreflex- and autonomic function and is able to describe adaption processes of baroreceptor circuit during cardiovascular stimulation. Hence, this novel algorithm may be a useful screening tool to detect abnormalities in cardiovascular adaption processes even when resting values appear to be normal

Signal processing techniques in heart rate and systolic arterial blood pressure variability studies

Power spectral analysis of heart rate and systolic arterial blood pressure variability provides a window to the activity of the autonomic nervous system. To derive power spectra from raw blood pressure and electrocardiogram signals, many steps of signal processing must be performed. Most popular methods of spectral analysis require evenly spaced samples; therefore interpolation and resampling techniques must be used. The results of the present study indicate that different interpolation techniques result in spectral distortions that vary depending upon the interpolation methods used as well as physiological parameters such as heart and respiration rate. Different interpolation methods applied to heart rate and systolic blood pressure data are compared and evaluated in an attempt to determine optimal interpolation methods for each type of data. Algorithms designed to derive systolic arterial pressure variability spectra from raw blood pressure data based on these results are also presented. These algorithms were used to perform analysis of blood pressure signals. The resulting systolic arterial pressure variability spectra were then compared to respiratory data as well as spectra of heart rate variability. A method was developed that provides a means of explaining the interaction of the parasympathetic and sympathetic influence on heart rate in terms of systolic arterial blood pressure and heart rate variability spectra

Role of sympathovagal imbalance in syncope using heart rate variability analysis

One of the common and challenging problems confronting the physician in clinical practice is recurrent syncope. Despite extensive evaluations, the causes of these cases Of syncope are not found in more than 40% of the patients. It is thought that most patients who experience unexplained syncope do so because of transient, unpredictable episodes of vasovagally mediated hypotension and bradycardia. It is hypothesized that impaired inhibition of parasympathetic tone during stress accompanies the development of syncope. Head-up tilt table testing reportedly provokes vasovagal episodes effectively in susceptible persons. This study attempts to explain the role played by the sympathetic and parasympathetic systems in the syncope condition. Heart Rate Variability, which has been demonstrated to be a reflection of the relative activities of sympathetic and parasympathetic systems, is utilized to compare the two groups of patients that took part. in the study. The comparisons were performed between a set of normal subjects and patients with previous history of syncope. The syncope group was again categorized on the basis of their response to the tilt, i.e. positive or negative to tilt. Patients who experienced symptoms of syncope during the test were grouped positive and those whodid not as negative. Analysis was performed in the time domain as well as frequency domain. In the time domain the HF (parasympathetic) and LF (sympathetic + parasympathic) activity was analyzed before tilt and when in the tilted position, as a function of time. In the frequency domain, the LF and HF areas were compared between the two groups. The LF/HF ratio was a major parameter of interest in understanding the sympathovagal balance during the test. It was found that in syncope patients the parasympathetic activity did not decrease when the patient was in the tilted position and also that their sympathetic activity did not pick up in response to the tilt as it does in normal subjects. This was clearly evident from the LF/HF analysis

Investigation of the baroreflex of the rat : steady state and dynamic features

The baroreflex is one of the most important feedback systems in the body to maintain blood pressure variation within the homeostatic range. In this dissertation, the important features of the carotid and aortic baroreflexes have been extensively investigated on ventilated, central nervous system intact, neuromuscular blocked (NMB) rats using different control system and signal processing tools. Studies have demonstrated that sinoaortic denervation (SAD) caused substantial increases in the blood pressure variability. Comparing the pre- and post-SAD blood pressure spectra, there was a significant increase of power in the very low frequency region (0.00195 -0.2 Hz), and a significant decrease of power in the low frequency region (0.2 - 0.6 Hz) after SAD. The dominant power change after SAD was in the very low frequency region of the blood pressure spectra. The carotid and aortic baroreflexes were accessed by volumetric manipulation of the carotid sinus and electrical manipulation of the aortic depressor nerve (ADN) using step and sinusoidal stimulations. Myelinated ADN-A fibers and myelinated + unmyelinated ADN-A+C fibers were accessed separately in the experiments. Results showed that the baroreflex functions as a \u27low-pass\u27 filter, with -3dB cutoff frequency at approximately \u3c0. I Hz. The major working area of the baroreflex system is in the VLF region of the blood pressure spectra. The estimated system transportation lag was 1.07s, which would cause the baroreflex system to oscillate at frequencies around 0.4 Hz. Analyses demonstrated that it is not likely that the baroreflex is activated only occasionally, such as in response to postural shifts, but operates continuously to bring the blood pressure into balance. It is theoretically and experimentally demonstrated that the absolute gain of the open-loop baroreflex system can be predicted by the ratio of the pre-and post- blood pressure amplitude spectra