DynPeak: an algorithm for pulse detection and frequency analysis in hormonal time series.

The endocrine control of the reproductive function is often studied from the analysis of luteinizing hormone (LH) pulsatile secretion by the pituitary gland. Whereas measurements in the cavernous sinus cumulate anatomical and technical difficulties, LH levels can be easily assessed from jugular blood. However, plasma levels result from a convolution process due to clearance effects when LH enters the general circulation. Simultaneous measurements comparing LH levels in the cavernous sinus and jugular blood have revealed clear differences in the pulse shape, the amplitude and the baseline. Besides, experimental sampling occurs at a relatively low frequency (typically every 10 min) with respect to LH highest frequency release (one pulse per hour) and the resulting LH measurements are noised by both experimental and assay errors. As a result, the pattern of plasma LH may be not so clearly pulsatile. Yet, reliable information on the InterPulse Intervals (IPI) is a prerequisite to study precisely the steroid feedback exerted on the pituitary level. Hence, there is a real need for robust IPI detection algorithms. In this article, we present an algorithm for the monitoring of LH pulse frequency, basing ourselves both on the available endocrinological knowledge on LH pulse (shape and duration with respect to the frequency regime) and synthetic LH data generated by a simple model. We make use of synthetic data to make clear some basic notions underlying our algorithmic choices. We focus on explaining how the process of sampling affects drastically the original pattern of secretion, and especially the amplitude of the detectable pulses. We then describe the algorithm in details and perform it on different sets of both synthetic and experimental LH time series. We further comment on how to diagnose possible outliers from the series of IPIs which is the main output of the algorithm.

Regulation of anti-Müllerian hormone production in the cow: a multiscale study at endocrine, ovarian, follicular, and granulosa cell levels.

Anti-Müllerian hormone (AMH) is an endocrine marker that can help predict superovulatory responses to treatments administered to cows for embryo production. However, the optimal time of the estrous cycle at which a blood test should be performed for a highly reliable prognosis has not yet been established. Moreover, little is known about the regulation of AMH production. To answer these questions, a study was designed to investigate the regulation of AMH production in cows selected for their high or low ovulatory responses to superovulation. At the granulosa cell level, AMH production was inhibited by follicle-stimulating hormone but enhanced by bone morphogenetic proteins. At the follicular level, the expression of AMH within the follicle was dependent on the stage of follicular development. At the ovarian level, the size of the pool of small antral growing follicles determined ovarian AMH production. At the endocrine level, AMH followed a specific dynamic profile during the estrous cycle, which occurred independently of the follicular waves of terminal follicular development. Cows selected for their high or low responses to superovulation did not differ in the regulation of AMH production, but cows with higher responses had higher plasma AMH concentrations throughout the cycle. The optimal period of the estrous cycle at which to measure AMH concentrations with the aim of selecting the best cows for embryo production was found to be at estrus and after Day 12 of the cycle. Based on this multiscale study, we propose a model that integrates the different regulatory levels of AMH production.

Validation of a semi-classical signal analysis method for stroke volume variation assessment: a comparison with the PiCCO technique.

This study proposes a Semi-Classical Signal Analysis (SCSA) method for stroke volume (SV) variations assessment from arterial blood pressure measurements. One of the SCSA parameters, the first systolic invariant (INVS1), has been shown to be linearly related to SV. To technically validate this approach, the comparison between INVS1 and SV measured with the currently used PiCCO technique was performed during a 15-min recording in 20 mechanically ventilated patients in intensive care. A strong correlation was estimated by linear regression and cross-correlation analysis (mean coefficient = 0.90 ± 0.01 SEM at the two tests).

Role of brainstem centers in cardiorespiratory phase difference during mechanical ventilation.

During mechanical ventilation, large inter-patient and intra-patient variations of the phase of respiratory sinus arrhythmia (RSA) were described. To determine whether these variations were neurally mediated, we compared the RSA phase between: (1) 12 control subjects, (2) 23 mechanically ventilated patients without brain injury (MV group) and (3) 12 brain dead, mechanically ventilated patients, whose central nervous functions were abolished (BD group). ECG and ventilatory flow were recorded during 15 min and the RSA phase was then continuously computed by complex demodulation. Control group exhibited RSA phases between 180° and 250° whereas an opposite pattern, between 0° and 90°, was observed in the BD group. For the two groups, the phase was stable over time. In the MV group, the RSA phases were distributed between 0° and 260°, with a greater variability over time than the other groups. Therefore, during mechanical ventilation, brainstem centers may induce large variations of the RSA phase, not synchronous with the mechanical effect of ventilation.

Positive end-expiratory pressure may alter breathing cardiovascular variability and baroreflex gain in mechanically ventilated patients.

BACKGROUND: Baroreflex allows to reduce sudden rises or falls of arterial pressure through parallel RR interval fluctuations induced by autonomic nervous system. During spontaneous breathing, the application of positive end-expiratory pressure (PEEP) may affect the autonomic nervous system, as suggested by changes in baroreflex efficiency and RR variability. During mechanical ventilation, some patients have stable cardiorespiratory phase difference and high-frequency amplitude of RR variability (HF-RR amplitude) over time and others do not. Our first hypothesis was that a steady pattern could be associated with reduced baroreflex sensitivity and HF-RR amplitude, reflecting a blunted autonomic nervous function. Our second hypothesis was that PEEP, widely used in critical care patients, could affect their autonomic function, promoting both steady pattern and reduced baroreflex sensitivity. METHODS: We tested the effect of increasing PEEP from 5 to 10 cm H2O on the breathing variability of arterial pressure and RR intervals, and on the baroreflex. Invasive arterial pressure, ECG and ventilatory flow were recorded in 23 mechanically ventilated patients during 15 minutes for both PEEP levels. HF amplitude of RR and systolic blood pressure (SBP) time series and HF phase differences between RR, SBP and ventilatory signals were continuously computed by complex demodulation. Cross-spectral analysis was used to assess the coherence and gain functions between RR and SBP, yielding baroreflex-sensitivity indices. RESULTS: At PEEP 10, the 12 patients with a stable pattern had lower baroreflex gain and HF-RR amplitude of variability than the 11 other patients. Increasing PEEP was generally associated with a decreased baroreflex gain and a greater stability of HF-RR amplitude and cardiorespiratory phase difference. Four patients who exhibited a variable pattern at PEEP 5 became stable at PEEP 10. At PEEP 10, a stable pattern was associated with higher organ failure score and catecholamine dosage. CONCLUSIONS: During mechanical ventilation, stable HF-RR amplitude and cardiorespiratory phase difference over time reflect a blunted autonomic nervous function which might worsen as PEEP increases.

Endogenous circannual rhythm in luteinizing hormone secretion: insight from signal analysis coupled with mathematical modelling.

In sheep, as in many vertebrates, the seasonal pattern of reproduction is timed by the annual photoperiodic cycle, characterized by seasonal changes in the day length. The photoperiodic information is translated into a circadian profile of melatonin secretion. After multiple neuronal relays (within the hypothalamus), melatonin affects gonadotrophin-releasing hormone (GnRH) secretion, which in turn controls ovarian cyclicity. The pattern of GnRH secretion is mirrored by that of luteinizing hormone (LH) secretion, whose plasmatic level can be easily measured. We addressed the question of whether there exists an endogenous circannual rhythm in a tropical sheep (Blackbelly) population that exhibits clear seasonal ovarian activity when ewes are subject to temperate latitudes. We based our analysis on LH time series collected in the course of 3 years from ewes subject to a constant photoperiodic regime. Owing to intra- and interanimal variability and unequal sampling times, the existence of an endogenous rhythm is not straightforward. We have used time-frequency signal processing methods, and especially the smooth pseudo-Wigner-Ville distribution, to extract possible hidden rhythms from the data. To further investigate the low-frequency (LF) and high-frequency (HF) components of the signals, we have designed a simple mathematical model of the LH plasmatic level accounting for the effect of experimental sampling times. The model enables us to (i) confirm the existence of an endogenous circannual rhythm as detected by the LF signal component, (ii) investigate the action mechanism of the photoperiod on the pulsatile pattern of LH secretion (control of the interpulse interval), and (iii) conclude that the HF component is mainly due to the experimental sampling protocol.

Anti-mullerian hormone is an endocrine marker of ovarian gonadotropin-responsive follicles and can help to predict superovulatory responses in the cow.

The major limitation to the development of embryo production in cattle is the strong between-animal variability in ovulatory response to FSH-induced superovulation, mainly due to differences in ovarian activity at the time of treatment. This study aimed to establish whether anti-Müllerian hormone (AMH) was an endocrine marker of follicular populations in the cow, as in human, and a possible predictor of the ovarian response to superovulation. Anti-Müllerian hormone concentrations in plasma varied 10-fold between cows before treatment and were found to be highly correlated with the numbers of 3- to 7-mm antral follicles detected by ovarian ultrasonography before treatment (r=0.79, P<0.001) and the numbers of ovulations after treatment (r=0.64, P<0.01). Between-animal differences in AMH concentrations were found to be unchanged after a 3-mo delay (r=0.87, P<0.01), indicating that AMH endocrine levels were characteristic of each animal on a long-term period. The population of healthy 3- to 7-mm follicles was the main target of superovulatory treatments, contained the highest AMH concentrations and AMH mRNA levels compared with larger follicles, and contributed importantly to AMH endocrine levels. In conclusion, AMH was found to be a reliable endocrine marker of the population of small antral gonadotropin-responsive follicles in the cow. Moreover, AMH concentrations in the plasma of individuals were indicative of their ability to respond to superovulatory treatments.

Breathing cardiovascular variability and baroreflex in mechanically ventilated patients.

Heart rate and blood pressure variations during spontaneous ventilation are related to the negative airway pressure during inspiration. Inspiratory airway pressure is positive during mechanical ventilation, suggesting that reversal of the normal baroreflex-mediated pattern of variability may occur. We investigated heart rate and blood pressure variability and baroreflex sensitivity in 17 mechanically ventilated patients. ECG (RR intervals), invasive systolic blood pressure (SBP), and respiratory flow signals were recorded. High-frequency (HF) amplitude of RR and SBP time series and HF phase differences between RR, SBP, and ventilatory signals were continuously computed by Complex DeModulation (CDM). Cross-spectral analysis was used to assess the coherence and the gain functions between RR and SBP, yielding baroreflex sensitivity indices. The HF phase difference between SBP and ventilatory signals was nearly constant in all patients with inversion of SBP variability during the ventilator cycle compared with cycling with negative inspiratory pressure to replicate spontaneous breathing. In 12 patients (group 1), the phase difference between RR and ventilatory signals changed over time and the HF-RR amplitude varied. In the remaining five patients (group 2), RR-ventilatory signal phase and HF-RR amplitude showed little change; however, only one of these patients exhibited a RR-ventilatory signal phase difference mimicking the normal pattern of respiratory sinus arrhythmia. Spectral coherence between RR and SBP was lower in the group with phase difference changes. Positive pressure ventilation exerts mainly a mechanical effect on SBP, whereas its influence on HR variability seems more complex, suggesting a role for neural influences.

Effect of heavy exercise on spectral baroreflex sensitivity, heart rate, and blood pressure variability in well-trained humans.

The aim of the study was to assess the instantaneous spectral components of heart rate variability (HRV) and systolic blood pressure variability (SBPV) and determine the low-frequency (LF) and high-frequency baroreflex sensitivity (HF-BRS) during a graded maximal exercise test. The first hypothesis was that the hyperpnea elicited by heavy exercise could entail a significant increase in HF-SBPV by mechanical effect once the first and second ventilatory thresholds (VTs) were exceeded. It was secondly hypothesized that vagal tone progressively withdrawing with increasing load, HF-BRS could decrease during the exercise test. Fifteen well-trained subjects participated in this study. Electrocardiogram (ECG), blood pressure, and gas exchanges were recorded during a cycloergometer test. Ventilatory equivalents were computed from gas exchange parameters to assess VTs. Spectral analysis was applied on cardiovascular series to compute RR and systolic blood pressure power spectral densities, cross-spectral coherence, gain, and alpha index of BRS. Three exercise intensity stages were compared: below (A1), between (A2), and above (A3) VTs. From A1 to A3, both HF-SBPV (A1: 45 +/- 6, A2: 65 +/- 10, and A3: 120 +/- 23 mm2Hg, P < 0.001) and HF-HRV increased (A1: 20 +/- 5, A2: 23 +/- 8, and A3:40 +/- 11 ms2, P < 0.02), maintaining HF-BRS (gain, A1: 0.68 +/- 0.12, A2: 0.63 +/- 0.08, and A3: 0.57 +/- 0.09; alpha index, A1: 0.58 +/- 0.08, A2: 0.48 +/- 0.06, and A3: 0.50 +/- 0.09 ms/mmHg, not significant). However, LF-BRS decreased (gain, A1: 0.39 +/- 0.06, A2: 0.17 +/- 0.02, and A3: 0.11 +/- 0.01, P < 0.001; alpha index, A1: 0.46 +/- 0.07, A2: 0.20 +/- 0.02, and A3: 0.14 +/- 0.01 ms/mmHg, P < 0.001). As expected, once VTs were exceeded, hyperpnea induced a marked increase in both HF-HRV and HF-SBPV. However, this concomitant increase allowed the maintenance of HF-BRS, presumably by a mechanoelectric feedback mechanism.

Arterial blood pressure analysis based on scattering transform II.

"Arterial blood pressure analysis based on scattering transform I" introduces a new method based on the scattering transform for a one dimensional Schrödinger equation to reconstruct the arterial blood pressure waves and separate its systolic and diastolic parts. In this article, we propose to analyse the parameters computed from this technique in different clinical and physiological conditions. Two cases are considered: moderate chronic heart failure and high fit triathletes. The variability of these new parameters is compared to the variability of classical blood pressure parameters. Promising results are obtained.

An algorithm for robust and efficient location of T-wave ends in electrocardiograms.

The purpose of this paper is to propose a new algorithm for T-wave end location in electrocardiograms, mainly through the computation of an indicator related to the area covered by the T-wave curve. Based on simple assumptions, essentially on the concavity of the T-wave form, it is formally proved that the maximum of the computed indicator inside each cardiac cycle coincides with the T-wave end. Moreover, the algorithm is robust to acquisition noise, to wave form morphological variations and to baseline wander. It is also computationally very simple: the main computation can be implemented as a simple finite impulse response filter. When evaluated with the PhysioNet QT database in terms of the mean and the standard deviation of the T-wave end location errors, the proposed algorithm outperforms the other algorithms evaluated with the same database, according to the most recent available publications up to our knowledge.

Heart rate variability during exercise performed below and above ventilatory threshold.

PURPOSE: To examine whether differences in heart rate variability (HRV) can distinguish sub- from supra-ventilatory-threshold exercise and whether the exercise duration at supra-threshold intensity alters cardiorespiratory synchronization. METHODS: Beat-to-beat RR interval, VO2, VCO2, VE, and blood lactate concentration of 11 healthy well-trained young subjects were collected during two exercise tests: 1) a moderate-intensity test: 15 min performed below the power at ventilatory threshold (pVT); and 2) a heavy-intensity test: above pVT until exhaustion. Fast Fourier transform, smoothed pseudo Wigner-Ville distribution, and complex demodulation were applied to RR time series. RESULTS: 1) Moderate exercise shows a prevalence of low-frequency (LF) spectral energy compared with the high-frequency (HF) one (LF = 80 +/- 10% vs HF = 20 +/- 10%, P < 0.001), whereas the reverse is observed during heavy exercise (LF = 11 +/- 8% vs HF = 89 +/- 8%, P < 0.001). 2) During heavy exercise, the HF amplitude and the tidal volume (Vt) remained constant, whereas the breathing frequency (BF) increased (BF: 0.70 +/- 0.18 vs 0.93 +/- 0.31, P < 0.01) and mean RR decreased (342 +/- 15 vs 317 +/- 16, P < 0.01). Despite the RR series and the breathing signal remaining synchronized, HR/BF ratio decreased and stabilized at 3 RR for one breathing cycle, whatever the initial ratio. CONCLUSION: 1) HRV allows us to differentiate sub- from supra-ventilatory-threshold exercise and 2) exercise duration at supra-threshold intensity does not alter the cardiorespiratory synchronization.

Cardiac autonomic control during balloon carotid angioplasty and stenting.

Hemodynamic alterations during balloon carotid angioplasty (BCA) and stenting have been ascribed to the consequences of direct carotid baroreceptor stimulation during balloon inflation. BCA with stenting in patients with carotid atheromatous stenoses offers a unique opportunity for elucidating the cardiovascular autonomic response to direct transient intravascular stimulation of the baroreceptors. We analysed the consequences of BCA on the autonomic control of heart rate and on breathing components in nine patients with atheromatous stenoses involving the bifurcation and the internal carotid. A time-frequency domain method, the smoothed pseudo-Wigner-Ville transform (SPWVT), was used to evaluate the spectral parameters (i.e., the instantaneous amplitude and centre frequency (ICF) of the cardiovascular and respiratory oscillations). Those parameters and their dynamics (8 and 24 h later) were evaluated during and after the procedure. BCA stimulates baroreceptors in all patients, which markedly reduces heart rate and blood pressure. Vagal baroreflex activation altered the respiratory sinus arrhythmia in terms of amplitude and frequency (ICF HF RR shifted from 0.27 +/- 0.03 to 0.23 +/- 0.04 Hz pre-BCA vs. BCA, respectively; p < 0.01). Both the high- and low-frequency amplitudes of heart rate oscillations were altered during carotid baroreceptor stimulation, strongly supporting a contribution of the baroreflex to the generation of both oscillations of heart rate. Carotid baroreceptors stimulation increased the inspiratory time (Ti) (1.5 +/- 0.5 to 2.3 +/- 0.6 s pre-BCA vs. BCA, respectively; p < 0.01). In awake patients, BCA with stenting of atheromatous stenosis involving the bifurcation and internal carotid causes marked changes in the cardiac autonomic and respiratory control systems.

Instantaneous parameter estimation in cardiovascular time series by harmonic and time-frequency analysis.

Time-frequency distributions, such as smoothed pseudo Wigner-Ville distribution (SPWVD), complex demodulation (CDM), and provide useful time-varying spectral parameter estimators. However, each of these methods has limitations that a joint utilization could largely reduce, due to their interesting complementary features. The aim of this paper is to validate the joint SPWVD-CDM method on synthetic and real cardiovascular time series with normal and reduced variability such as in autonomic blockade or autonomic deficiency. We propose two indexes related to the noise present in the signal and to the dispersion of the power spectrum in order to validate instantaneous parameter estimation. In the low-frequency band, the interpretation of the instantaneous frequency and phase of cardiovascular time-series should be discarded in many real-life situations. Conversely, in the high frequency band, under paced breathing, the reliability of the instantaneous parameters is demonstrated even in conditions of reduced cardiovascular variability.