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Anti-Mullerian 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.

International audience; 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).

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 endexpiratory 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.

RR intervals of ten elite trotting horses were recorded during an interval training session performed on track. This study examined two hypotheses. Firstly, like in humans, the hyperpnea combined with a decrease in cardiac autonomic control on heart rate during heavy exercise could result in a prevalence of high frequency heart rate variability. Secondly, this prevalence could increase with the heavy exercise repetition. Two exercise intensities were compared: moderate (ME) and heavy (HE). Furthermore, heavy exercise repetitions were compared between the beginning and the end of the interval training session. When comparing ME and HE periods: heart rate was significantly lower (155 +/- 12 vs. 210 +/- 9 ms, p < 0.001), LF spectral energy (0.04 - 0.2 Hz) was significantly higher (ME: 6.94 +/- 4.80 and HE: 0.24 +/- 0.14 ms(2) . Hz (-1), p < 0.001) whereas HF (0.2 - 2 Hz) was significantly lower (ME: 7.09 +/- 2.24 and HE: 10.60 +/- 3.64 ms(2) . Hz (-1), p < 0.05). In relative terms, ME showed similar results in both LFn (LF/LF+HF) and HFn (HF/LF+HF) whereas HE showed a large prevalence of HFn energy compared to LFn (p < 0.001). The difference in LF/HF ratio between the two exercise conditions was significant (1.14 +/- 0.92 vs. 0.09 +/- 0.12, p < 0.001). Exercise repetition induced a significant increase in heart rate between the beginning and the end of the interval training session (207 +/- 10 beats . min (-1) vs. 212 +/- 9 beats . min (-1), p < 0.001) whereas LF energy decreases (1.54 +/- 1.65 vs. 0.32 +/- 0.24 ms(2) . Hz (-1), p < 0.01) and HF energy remained constant (10.79 +/- 4.10 vs. 10.40 +/- 3.35 ms(2) . Hz (-1), NS). This study confirmed the results observed in humans during heavy exercise conditions with a large prevalence of HF in contrast to LF, this prevalence increasing with exercise repetitions. The observed decrease in LF/HF ratio could provide an index of hyperpnea in horses during interval training.

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.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.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%, P0.001), whereas the reverse is observed during heavy exercise (LF = 11 +/- 8% vs HF = 89 +/- 8%, P0.001). 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, P0.01) and mean RR decreased (342 +/- 15 vs 317 +/- 16, P0.01). 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.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.

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.

Aims: With the complex demodulation (CDM) method, we assessed the instantaneous amplitude and frequency of cardiovascular (CV) and respiratory oscillations, and the instant phase (IP) between the CV and respiratory signals using respiration as a periodic forced stimulation. We hypothesised a possible lack of synchronisation between CV and respiratory signals under regular breathing at different frequencies. Methods: RR interval (ECG), blood pressure (SBP/DBP, Finapress), respiration (Respitrace) were monitored during two random-order periods of voluntary paced-breathing (0.15 Hz/0.25 Hz) in 10 moderate CHF patients and 10 age-matched controls. The CDM method provides the amplitude and frequency of a particular spectral component as a function of time in both LF and HF bands. IP between CV and respiratory oscillations was assessed using the real modulating breathing rate. Results: (i) Continuous phase variations between CV oscillations and the respiratory signal were evidenced in CHF patients, the slower the breathing rate, the greater the phase variation (RR/Resp; 0.25 Hz, 23±17°; 0.15 Hz, 46±57°, P

Respiratory sinus arrhythmia (RSA) estimation is commonly used as a non-invasive index of cardiac vagal tone. To test this relationship, vagal tone was augmented or blocked using atropine. The study was carried out using 14 healthy volunteers, following beta-adrenoceptor blockade (10 mg bisoprolol per os) and during controlled respiration (0.25 Hz) in order to limit the confounding effects of cardiac sympathetic tone and respiration pattern changes. Atropine was slowly infused intravenously over a 30-min period up to a vagolytic cumulative dose of 0.04 mg/kg. The instant vagal tone was compared to the instant RSA value obtained from a time-/frequency-domain analysis of pulse interval (PI). RSA and PI varied in the same direction with an initial increase corresponding to the early vagomimetic effect of atropine followed by a decrease during the vagolytic phase. The comparative percentage fluctuations of RSA and PI over this large vagal tone range indicate that RSA is more sensitive (about twofold) than PI in reflecting fluctuations around the set point. This dissociated behaviour of PI and heart rate variability could be important to our understanding of the circulatory changes that result from fluctuations in vagal inputs to the sinus node.

Heart rate varies with respiration, blood pressure, emotion, etc., and heart rate variability (HRV) is presently one of the best indices to predict fatal issues in cardiac failure and after myocardial infarction. HRV depends on various reflexes. In addition, parallel studies of HRV and the myocardial adrenergic and muscarinic transduction system in experimental models of cardiac hypertrophy (CH) have suggested that the myocardial phenotype at the sinus-node level may also play a role. A transgenic strain of mice with atrial overexpression of the beta 1-adrenergic receptors was generated with attenuated HRV, which demonstrates that the phenotype itself is a determinant of HRV. HRV is explored by noninvasive techniques, including simple determination of the standard error of the mean, time-domain analysis, and Fourier transformation. We recently developed a time and frequency domain method of analysis, the smoothed pseudo-Wigner-Ville transformation, which allows better exploration of nonstationarity. Nonlinear methods have also been applied due to the extreme complexity of the biological determinants, and have provided evidence of a chaotic attractor in certain conditions. It is proposed that in steady state a very simple process, which is not completely deterministic, could better explain intermit interval regulations than chaotic behavior. In contrast, under extreme circumstances the regulation proceeds using chaotic behavior. Arrhythmias and HRV can be quantitated in 16-month-old unanesthetized spontaneously hypertensive rats (SHR). Ventricular premature beats are more frequent in SHR than in age-matched controls; they disappear after converting enzyme inhibition (CEI) relative to the reduction of both cardiac hypertrophy and ventricular fibrosis. HRV is attenuated in SHR, as it is in compensatory CH in humans. When CH is prevented, HRV returns to normal. CEI is therefore antiarrhythmic. Another pharmacological application of this concept concerns the bradycardic agents that may improve HRV.

Cardiac failure is a disease which involves three different mechanisms: (1) the limits and imperfections of the general process of myocardial adaptation to mechanical stress, which includes various changes in genetic expression, including an increased collagen mass, but an unchanged collagen concentration; (2) the limits and imperfections of the adaptational process at the peripheral level which allows the entire organism to adapt to the low cardiac output; (3) fibrosis, an augmented collagen concentration, which is not a direct consequence of mechanical overload, but depends on aging, myocardial ischemia or hormonal changes. Middle-aged spontaneously hypertensive rats (SHRs) represent a good model of the common clinical situation. Three-month treatment with a CEI reduces, in parallel, arterial hypertension, left ventricular hypertrophy and ventricular fibrosis. Holter monitoring was also performed in these animals. Untreated SHRs when compared to age-matched Wistar rats have an increased number of ventricular premature beats which are suppressed by the treatment. In addition, heart rate variability has been quantified by using the pseudo Wigner-Villé transformation, a time and frequency domain method. The low frequency oscillations are hampered in SHRs. CEI normalizes this parameter.

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., Comment: Nombre de pages : 35 ; Nombre de figures : 16 ; Nombre de tableaux : 1

International audience; In the realm of multiscale signal analysis, multifractal analysis provides with a natural and rich framework to measure the roughness of a time series. As such, it has drawn special attention of both mathematicians and practitioners, and led them to characterize relevant physiological factors impacting the heart rate variability. Notwithstanding these considerable progresses, multifractal analysis almost exclusively developed around the concept of Legendre singularity spectrum, for which efficient and elaborate estimators exist, but which are structurally blind to subtle features like non-concavity or, to a certain extent, non scaling of the distributions. Large deviations theory allows bypassing these limitations but it is only very recently that performing estimators were proposed to reliably compute the corresponding large deviations singularity spectrum. In this article, we illustrate the relevance of this approach, on both theoretical objects and on human heart rate signals from the Physionet public database. As conjectured, we verify that large deviations principles reveal significant information that otherwise remains hidden with classical approaches, and which can be reminiscent of some physiological characteristics. In particular we quantify the presence/absence of scale invariance of RR signals.

To assess the influence of intrauterine growth retardation on heart rate (HR) and HR variability during sleep, we performed polygraphic recordings in 10 small-for-gestational age (SGA) and 16 appropriate-for-gestational age (AGA) newborns. Both groups were clinically and neurologically normal and were at 37 to 41 wk conceptional age. RR intervals were analyzed using the short-time Fourier transform in three frequency bands: 1) high frequency, with a period 3-8 heartbeat; 2) mid frequency, with a period 10-25 heartbeat; and 3) low frequency, with a period 30-100 heartbeat. In both active and quiet sleep, SGA newborns significantly differed from AGA newborns by having a shorter RR interval (p < 0.01) and lower amplitude of HR variability in all bands (p < 0.05) except low frequency in quiet sleep. Quiet sleep differed from active sleep by having a longer RR interval (p < 0.05), higher high-frequency variability (p < 0.02) in both SGA and AGA newborns, and lower low-frequency variability (p < 0.005 for AGA newborns). Our data give evidence of clear modifications of both sympathetic and parasympathetic HR control in the at-risk SGA population. Similarity of between-state characteristics suggests maintained CNS control of HR in SGA as well as in AGA newborns. We speculate that between-group HR and HR variability differences may be related to augmented metabolic rate in SGA compared with AGA newborns.

National audience; The assessment of autonomic nervous system (ANS) efficiency is mainly based on baroreflex gain and heart rate variability, which both have a prognostic value in cardiovascular diseases and critically ill patients. Newly developed software, allowing automatic calculation of heart rate variability, could improve the ANS assessment in critical care patients. Mechanical ventilation has been shown to increase baroreflex gain and heart rate variability in several respiratory diseases associated with an impaired autonomic function (obstructive sleep apnea, chronic obstructive pulmonary disease), mostly during long-term application. Due to methodological considerations, this beneficial effect has not been demonstrated in critical care patients, in whom the use of high levels of PEEP could even worsen the ANS by decreasing baroreflex gain and heart rate variability, possibly through hemodynamic effects. The development of new ventilatory modes could be beneficial in terms of ANS: NAVA (neurally adjusted ventilatory assist) improves the physiological respiratory variability, and fractal ventilation enhances respiratory sinus arrhythmia, which could, according to some authors, improve gas exchanges. In contrast, ANS assessment could make easier the weaning from mechanical ventilation, as a decrease in heart rate variability during weaning trials seems predictive of weaning failure.; En clinique, l'efficience du système nerveux autonome (SNA) est estimée principalement par le gain du baroréflexe et la variabilité de la fréquence cardiaque, qui ont une valeur pronostique dans de nombreuses pathologies, notamment cardiovasculaires mais aussi en réanimation. L'évaluation du SNA, largement utilisée en cardiologie par exemple, pourrait bénéficier en réanimation de l'apparition de logiciels de calcul automatique de la variabilité cardiaque. Quant à la ventilation mécanique (VM), appliquée à des pathologies respiratoires associées à une dysfonction autonome (apnées du sommeil, bronchopneumopathie chronique obstructive [BPCO]), et le plus souvent de façon chronique, elle augmente la variabilité cardiaque et le gain du baroréflexe. En raison surtout de difficultés méthodologiques, cet effet bénéfique n'a cependant pas été démontré en situation aiguë, chez les patients de réanimation, où l'utilisation de hauts niveaux de PEEP pourrait même être délétère pour le SNA, réduisant la variabilité cardiaque et le gain du baroréflexe, possiblement par le biais d'effets hémodynamiques. Le développement de nouveaux modes ventilatoires, plus proches de la physiologie de la respiration, pourrait être bénéfique en termes de SNA: la NAVA (neurally adjusted ventilatory assist) favorise la variabilité respiratoire physiologique, et la ventilation fractale augmente l'amplitude de l'arythmie sinusale respiratoire (ASR), dont certains pensent qu'elle pourrait participer à l'amélioration des échanges gazeux. L'évaluation du SNA pourrait, à l'inverse, améliorer la prise en charge ventilatoire des patients, et notamment du sevrage ventilatoire, puisque la baisse de la variabilité cardiaque au cours des épreuves de sevrage semble prédictive de son échec.

To investigate the influence of prematurity and postnatal age on the maturation of the autonomic nervous system function, we analysed heart-rate and heart-rate variability in twelve prematurely born infants (< 37 weeks gestational age) reaching the conceptional age of 37-41 weeks. These neonates were compared with sixteen 37-41 week conceptional age newborns (< 10 days postnatal age). Heart-rate variability was analysed by spectral analysis of interbeat intervals using Short-Time Fourier Transform. We found that during both active and quiet sleep, the durations of RR-intervals were shorter and the amplitude of heart-rate variability in different frequency bands was lower in prematures reaching term than in newborns of the same conceptional age (P < 0.001). Between-state comparison showed differences in both groups. In both groups, low-frequency heart-rate variability was higher in active sleep than in quiet sleep. Between-state differences of RR-intervals and high-frequency heart-rate variability were present only in newborns (P < 0.01). Discrimination between newborns and prematures reaching term, based on RR-intervals and heart-rate variability, was correct in both sleep states with errors between 7 to 16%. However, in both newborns and prematures reaching term, between-state discrimination showed less reliable results, especially for quiet sleep discrimination with 24% (in PRT) and 20% (in NB) of errors. Our results, especially information given by factor analysis, suggest that the differences between newborns and prematures reaching term, concerning RR-interval and heart-rate variability, may be related to a changed balance between the sympathetic and parasympathetic nervous systems with a diminished parasympathetic component of heart rate control in prematures reaching term, as compared to newborns.

National audience; The strong between-animal variability in the number of ovulations and embryos produced after ovarian stimulation by gonadotropins is a major limit to the development of embryo biotechnologies in cattle. In reproductive medicine, anti-mullerian hormone (AMH) is now widely used as an endocrine marker of the ovarian follicular reserve. In the cow, as in the woman, AMH is secreted by the granulosa cells of growing follicles. We have shown recently that in the cow, AMH is a very good endocrine marker of the population of small antral follicles that constitute the direct target of ovarian stimulatory treatments. AMH concentration measured in plasma before treatment varies between animals and is positively correlated to the number of ovulations and transferable embryos produced after an ovarian stimulatory treatment. Interestingly, AMH concentrations can remain stable over several months for each animal. Moreover, the number of embryos produced after ovarian stimulation is highly repeatable and has a relatively good heritability. From these observations, we propose the determination of AMH concentration in the plasma of a potential donor cow as a simple predictive method to evaluate both its level of ovarian activity and its capacity to produce high or low numbers of embryos. Optimal conditions for implementing this diagnostic test in cattle remain to be defined considering the age, the breed, the physiological status and the environmental factors related to breeding conditions for each animal.; Chez les bovins, l'existence d'une forte variabilité entre animaux du nombre d'ovulations et du nombre d'embryons produits après stimulation ovarienne constitue une limite majeure au développement des biotechnologies de l'embryon. Nous avons montré récemment que chez la vache, comme chez la femme, l'hormone antimüllérienne (AMH), sécrétée par les cellules de granulosa des follicules en croissance, est un très bon marqueur endocrinien de la folliculogenèse basale et, en particulier de la population de petits follicules à antrum qui est la principale cible des traitements de stimulation ovarienne utilisant des hormones gonadotropes. Les concentrations plasmatiques d'AMH mesurées avant traitement sont variables entre animaux et positivement corrélées aux nombres d'ovulations et d'embryons transférables produits après traitement de stimulation ovarienne. En revanche, pour un même animal, les concentrations plasmatiques d'AMH apparaissent stables sur une durée de plusieurs mois. En parallèle, il existe une bonne répétabilité individuelle et une relativement bonne héritabilité du nombre d'embryons produits après stimulation ovarienne. Ces résultats permettent de proposer la mesure de la concentration plasmatique d'AMH comme une méthode prédictive simple d'évaluation du niveau d'activité ovarienne et de la capacité de production d'embryons par une vache donneuse potentielle. Les conditions optimales pour la réalisation de ce diagnostic, prenant en compte l'âge de l'animal, sa race, son état physiologique et les facteurs environnementaux liés à ses conditions d'élevage, restent encore à définir.

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.

International audience; 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.

To assess maturation of the Autonomic Nervous System (ANS) and sleep states, Heart Rate Variability (HRV) was studied in 24 healthy sleeping newborns, aged from 31 to 41 weeks, conceptional age (CA). Spectral analysis of the interbeat interval (RR) signal, was performed by Short-Time Fourier Transform, in three frequency bands: high (HF), of purely vagal origin, mid (MF), and low (LF), vagal and sympathetic, thus allowing evaluation of both branches of the ANS, observed in Active Sleep (AS = REM Sleep) and in Quiet Sleep (QS = nREM Sleep). Principal Component Analysis, Discriminant Analysis, and hypothesis tests were used to investigate the evolution of spectral variables and their relation with sleep states. HF, MF, LF, and mean RR all increased with age; the differences from the premature to the full-term group, were more marked, as a whole, in AS than in QS. HF showed the highest increase from the premature (31-36 weeks CA) to the intermediate (37-38) group, whereas LF showed equal differences from the premature to the intermediate, and from the intermediate to the full-term (39-41) groups. These results suggest a steep increase in vagal tone at 37-38 weeks CA, with stability afterwards, and a more regular increase in sympathetic tone from 31 to 41 weeks CA.

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.

International audience; 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

International audience; 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 α 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 andlt; 0.001) and HF-HRV increased (A1 20 ± 5, A2 23 ± 8, and A340 ± 11 ms2, P andlt; 0.02), maintaining HF-BRS (gain, A1 0.68 ± 0.12, A2 0.63 ± 0.08, and A3 0.57 ± 0.09; α index, A1 0.58 ± 0.08, A2 0.48 ± 0.06, and A3 0.50 ± 0.09 ms/mmHg, not significant). However, LFBRS decreased (gain, A1 0.39 ± 0.06, A2 0.17 ± 0.02, and A3 0.11 ± 0.01, P andlt; 0.001; α index, A1 0.46 ± 0.07, A2 0.20 ± 0.02, and A3 0.14 ± 0.01 ms/mmHg, P andlt; 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. Copyright © 2008 the American Physiological Society.

The present study examined whether the ventilatory thresholds during an incremental exhaustive running test could be determined using heart rate variability (HRV) analysis. Beat-to-beat RR interval, V(.-)O (2), V(.-)CO (2) and V(.-) (E) of twelve professional soccer players were collected during an incremental test performed on a track until exhaustion. The "smoothed pseudo Wigner-Ville distribution" (SPWVD) time-frequency analysis method was applied to the RR time series to compute the usual HRV components vs. running speed stages. The ventilatory equivalent method was used to assess the ventilatory thresholds (VT1 and VT2) from respiratory components. In addition, ventilatory thresholds were assessed from the instantaneous components of respiratory sinus arrhythmia (RSA) by two different methods: 1) from the high frequency peak of HRV ( FHF), and 2) from the product of the spectral power contained within the high frequency band (0.15 Hz to fmax) by FHF (HF x FHF) giving two thresholds: HFT1 and HFT2. Since the relationship between FHF and running speed was linear for all subjects, the VTs could not be determined from FHF. No significant differences were found between respective running speeds at VT1 vs. HFT1 (9.83 +/- 1.12 vs. 10.08 +/- 1.29 km x h (-1), n.s.) nor between the respective running speeds at VT2 vs. HFT2 (12.55 +/- 1.31 vs. 12.58 +/- 1.33 km x h (-1), n.s.). Linear regression analysis showed a strong correlation between VT1 vs. HFT1 (R (2) = 0.94, p < 0.001) and VT2 vs. HFT2 (R (2) = 0.96, p < 0.001). The Bland-Altman plot analysis reveals that the assessment from RSA gives an accurate estimation of the VTs, with HF x FHF providing a reliable index for the ventilatory thresholds detection. This study has shown that VTs could be assessed during an incremental running test performed on a track using a simple beat-to-beat heart rate monitor, which is less expensive and complex than the classical respiratory measurement devices.

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.

The purpose of this study was to implement a new method for assessing the ventilatory thresholds from heart rate variability (HRV) analysis. ECG, VO2, VCO2, and VE were collected from eleven well-trained subjects during an incremental exhaustive test performed on a cycle ergometer. The "Short-Term Fourier Transform" analysis was applied to RR time series to compute the high frequency HRV energy (HF, frequency range: 0.15 - 2 Hz) and HF frequency peak (fHF) vs. power stages. For all subjects, visual examination of ventilatory equivalents, fHF, and instantaneous HF energy multiplied by fHF (HF.fHF) showed two nonlinear increases. The first nonlinear increase corresponded to the first ventilatory threshold (VT1) and was associated with the first HF threshold (T(RSA1) from fHF and HFT1 from HF.fHF detection). The second nonlinear increase represented the second ventilatory threshold (VT2) and was associated with the second HF threshold (T(RSA2) from fHF and HFT2 from HF.fHF detection). HFT1 , T(RSA1), HFT2, and T(RSA2) were, respectively, not significantly different from VT1 (VT1 = 219 +/- 45 vs. HFT1 = 220 +/- 48 W, p = 0.975; VT1 vs. T(RSA1) = 213 +/- 56 W, p = 0.662) and VT2 (VT2 = 293 +/- 45 vs. HFT2 = 294 +/- - 48 W, p = 0.956; vs. T(RSA2) = 300 +/- 58 W, p = 0.445). In addition, when expressed as a function of power, HFT1, T(RSA1), HFT2, and T(RSA2) were respectively correlated with VT1 (with HFT1 r2 = 0.94, p < 0.001; with T(RSA1) r2 = 0.48, p < 0.05) and VT2 (with HFT2 r2 = 0.97, p < 0.001; with T(RSA2 )r2 = 0.79, p < 0.001). This study confirms that ventilatory thresholds can be determined from RR time series using HRV time-frequency analysis in healthy well-trained subjects. In addition it shows that HF.fHF provides a more reliable and accurate index than fHF alone for this assessment.

International audience; Automatic detection of electrocardiograms (ECG) waves provides important information for cardiac disease diagnosis. A new T wave end location algorithm based on multi-lead ECG processing is proposed in this paper. A statistical hypothesis testing algorithm is applied to two auxiliary signals computed by filtering and differentiating ECG signals. The performance of the algorithm has been evaluated using the PhysioNet QT database. The standard deviation of the errors between automatic annotations and manual ones are within tolerance accepted by cardiologist.

A new algorithm is proposed in this paper for T-wave end location in electrocardiogram (ECG). It mainly consists of the computation of an indicator related to the area covered by the T-wave curve and delimited in a special manner. Based on simple assumptions, essentially on the concavity of the T-wave form, it is proved that the maximum of the computed indicator inside each cardiac cycle coincides with the T-wave end. The algorithm is robust to measurement 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 (FIR) filter

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.Key words: carotid angioplasty, heart rate variability, autonomic nervous system, respiration, spectral analysis.

To study the autonomic nervous system maturation in newborns, the authors analyzed the heart rate variability in correlation with sleep states and body movements. They used SIGNAL, a data flow parallel and synchronous language, designed for real time system programming. It answers the needs of this heart rate analysis sytem by processing large amounts of polygraphic signals at various sampling rates, and expressing relationships among their rhythms. The methods used and the implementation in the SIGNAL language are described. >

To assess the Autonomic Nervous System development in iron-deficient anemic infants during quiet sleep, the authors used the modified complex demodulation analysis which allows for a continuous evaluation of the phase and amplitude relationships between the heart rate and breathing oscillations. Iron deficient infants have a lower demodulation amplitude and more time spent in isolated sudden phase shifts than the control infants, suggesting a delayed autonomic nervous system maturation, especially in vagal activity.

Heart rate variability (HRV) analysis of 24 healthy newborn sleeping babies was performed by a short-time Fourier transform in three frequency bands, reflecting the activity of both branches of the autonomic nervous system (ANS), vagal and sympathetic. The means of the three extracted time signals, computed over records of 512 heartbeats, were used as a material for principal component analysis, and for discriminant factor analyses, to separate sleep states and conceptional age (CA) groups. This study suggests that sleep state discrimination, on the basis of an opposition between high (purely vagal in its origin) and low (vagal and sympathetic) frequency HRV, is regularly improved from 31 to 41 weeks CA; and a strong increase in ANS activity, mainly vagal, as reflected by high-frequency HRV, occurs precociously, not later than 38 weeks CA. >

To assess the autonomic nervous system development in iron-deficient anemic infants during sleep, we applied the discrete wavelet transform to perform heart rate variability analysis. The method provides suitable frequency resolution in the low-frequency domain, which is the domain of physiological interest. Significant differences between iron-deficient and control infants are shown in both quiet and active (REM) sleep, suggesting an autonomic dysfunction or delay in anemic infants.

Describes a set of methods to process polygraphic recordings. This parallel signal processing approach has the advantage to produce a condensed representation of the different physiological rhythms (heart rate, blood pressure, motility, ...) and a set of cardiovascular parameters related to an event, for example periodic leg movements (PLM). Important cardiovascular changes during the PLM are quantified with this methodology and reveal new possible insights for a better understanding of the disease. This analysing methodology is a general one that can be used to a large variety of polygraphic recordings concerning the cardiovascular system.

The nocturnal periodic leg movements (PLM) disease is not well known, especially in its relationship with cardiovascular (CV) rhythms. To address this question, the authors processed a standard polysomnographic recording in a typical patient, using the LARY-C software. A time-frequency analysis, using the smoothed pseudo Wigner-Ville transform was done to follow the autonomic nervous system (ANS) behavior through the short time variations of heart rate (HR) and arterial blood pressure (ABP) accompanying a PLM. The synchronous language SIGNAL, well suited for studying relationships between rhythms, was used to automatically produce a set of cardiovascular parameters related to a PLM. Important CV changes were quantified. The study of delays between CV and motor perturbations reveals new possible insights on PLM physiopathology.

The autonomic control of heart rate and blood pressure during sleep is controversial: although it has been reported that vagal activity is more often lower in rapid eye movement sleep (REM) than in other stages of sleep (non-REM, NREM), the opposite has also been described. Initially, it was reported that baroreflex sensitivity (BRS) increases during sleep (REM and NREM), but in later studies, this was only partially confirmed. We therefore studied autonomic control of the cardiovascular (CV) system during sleep in 12 normal adults. The spectral components of the heart rate R-R interval, blood pressure (BP), and BRS were computed at low (LF) and actual breathing frequency (high frequency, HF). Analysis of sleep stage and a cycle-by-cycle stage II analysis were performed. CV variability is affected largely by sleep-stage and sleep-cycle organisation: NREM and the last cycle exhibit the greatest vagal activity and the lowest sympathetic activity. BRS estimation for both the LF and HF bands confirmed previous results obtained by pharmacological and spontaneous slope methods: BRS is greater during sleep than during nocturnal wake periods, and further increased in REM. BRS is frequency dependent: in NREM, the higher value of HF BRS compared to LF BRS favours the HF control of BP variability, whereas higher BRS HF and LF components contribute to the strongest control in REM. BRS variability exhibits no significant pattern during the night. Our results suggest that both sleep-cycle organisation and BRS estimation in the LF and HF bands should be considered in sleep studies of autonomic CV control.

Background: We assessed the behavior of the baroreflex (BR) gain in chronic heart failure (CHF) patients using the spectral analysis method during application of a forcing stimulus, i.e. respiration. Methods: Simultaneous RR interval and arterial pressure fluctuation recordings were obtained during two random-order periods of voluntary paced-breathing (0.15 Hz and 0.25 Hz) in seven patients with moderate CHF (NYHA class II/III; EF, 30 ± 9%; peak VO2, 18 ± 5 ml kg−1 min−1) and six age-matched controls. BR gain was assessed in the time (sequential method) and frequency (cross-spectral gain in the low and high frequency) domains. Results: Slower breathing was associated with a BR gain decrease in CHF patients whereas a BR gain increase was evidenced in controls (BR gain: 6 ± 5 ms mmHg−1 at 0.25 Hz vs. 4 ± 3 ms mmHg−1 at 0.15 Hz, P < 0.05 in CHF; BR gain: 12 ± 7 ms mmHg−1 at 0.25 Hz vs. 15 ± 7 ms mmHg−1 at 0.15 Hz, P < 0.05 in controls). Conclusions: Voluntary breathing, which involves cortical centers in the brain, had major effects on cardiovascular system controller gain in CHF patients, indicating an impairment of the central neural regulation of the autonomic outflow.

Abstract —We quantified the repolarization time (so-called QT interval) in a rat, an animal species that does not show a well-characterized T wave on surface ECG. We used spontaneously hypertensive rats (SHR) and converting enzyme inhibition to demonstrate a reversible increase in QT interval in pressure-overloaded hearts in the absence of ischemia. An implanted telemetry system recording ECG data in freely moving rats was used to automatically calculate the RR interval. The QT duration was manually determined by use of a calibrated gauge, and a time-frequency domain analysis was used to evaluate heart rate variability. Left ventricular mass was sequentially assessed by echocardiography. Before treatment, 12-month-old SHR had higher left ventricular mass, QT and RR intervals, and unchanged heart rate variability compared with age-matched Wistar rats. A 2-month converting enzyme inhibition treatment with trandolapril reduces systolic blood pressure, left ventricular mass, and QT interval. The RR interval and heart rate variability remains unchanged. There is a positive correlation between the QT interval and left ventricular mass. The SHR is suitable for longitudinal studies on the QT interval. Thus, the detection of the QT interval reflects the phenotypic changes that occur during mechanical overload and, on the basis of these criteria, allows an in vivo determination of the adaptational process.

Heart rate is a function of at least three factors located in the sinus node, including the pacemaker and the activity of the sympathetic and vagal pathways. Heart rate varies during breathing and exercising. The is far from being a purely academic question because, after myocardial infarction or in cardiac insufficiency, reduced heart rate variability (HRV) represents the most valuable prognostic factor. HRV is usually considered index of the sympathovagal balance and is explored using time domain analysis, such as spectral analysis. Nevertheless, methods such as the Fast Fourier Transformation are not applicable to small rodents which have an unstable heart rate with asymmetric oscillations. Nonlinear methods show chaotic behavior under some conditions. A time and frequency domain method of analysis, the Wigner-Ville Transform, has been proposed for the study of HRV in both humans and small rodents, as a compromise between linear and nonlinear methods. We developed a method to quantify both arrhythmias and HRV in unanesthetized rodents. Such a method allows study of the relationship between the physiological parameters and the myocardial phenotype. Ventricular premature beats are more frequent in 16-month-old spontaneously hypertensive rats than in age-matched controls. In addition, HRV is attenuated in spontaneously hypertensive rats, as in compensatory cardiac hypertrophy in humans, and such attenuation is considered a prognostic index. Converting enzyme inhibition reduces in parallel arterial hypertension, cardiac hypertrophy, and ventricular fibrosis; it prevents ventricular premature beats and normalizes heart rate variability. It can be demonstrated that the incidence of ventricular premature beats is linked to the myocardial phenotype in terms of both cardiac hypertrophy and fibrosis. The two factors act as independent variables. HRV is correlated with the incidence of arrhythmias, suggesting that the beneficial effects of converting enzyme inhibition are related to prevention of arrhythmias.

To complete traditional time- and frequency-domain analyses, new methods derived from non-linear systems analysis have recently been developed for time series studies. A panel of the most widely used methods of heart rate analysis is given with computations on mouse data, before and after a single atropine injection.

The aim of our study was to assess differences in autonomic nervous system control during the various sleep states according to age, and to evaluate the influence of some "risk" factors upon this control. Criteria considered were RR intervals and their variability in different frequency bands: a) High frequency (HF)=3 to 8 heartbeat period (HBP); b) Mid Frequency (MF) = 10 to 25 HBP and c) Low Frequency (LF)=30 to 100 HBP. LF variability is mainly under sympathetic control, while vagal reflex mechanisms are involved in HF control (1).

In order to study maturation of the Autonomie Nervous System (ANS), we wanted to analyse Heart Rate Variability (HRV) in correlation with other biological signals; searching for a fast way to implement and calibrate the methods we are investigating, we used SIGNAL, a data flow, parallel, synchronous language, designed for real time system programming. This language allows a user to describe the processing of large polygraphic signals at various sampling rates, by expressing relationships among their rhythms. It is suitable for research purposes (assessement of methods with real time simulation) as well as clinical purposes (possible concurrent processing on a multiprocessor).

Background Spectral analysis of heart rate (HR) variability (HRV) requires, as a rule, some level of stationarity and, as a result, is inadequate to quantify biological transients. A time-/frequency-domain method (TF) was developed to obtain an instant spectral power (SP) of HRV during tilt. Methods and Results HR was recorded by Holter monitoring in volunteers and analyzed with a TF, the smoothed pseudo–Wigner-Ville transformation (SPWVT), with the table inclination randomly set or continuously increased while the table rotated in head-up position. (1) The SPWVT assesses, beat by beat, the instant center frequency (ICF) of the SP. ICF correlates better with instant HR than the ratio of low- (LF) to high-frequency (HF) oscillations. The transient effect of tilt is better characterized as a shift of SP toward lower frequencies than by changes in amplitudes. (2) The method evidences variations of HR from one second to another. During the passage to head-up position, the vagal withdrawal and the sympathetic activation occur nearly simultaneously, as indicated by the instant changes in both LF and HF amplitudes and ICF. (3) The averaged results of the SPWVT give results similar to those previously obtained with autoregressive algorithms. Conclusions The SPWVT is a new tool to explore HR transitions such as periods before episodes of arrhythmias on a time scale of one beat and allows quantification of an instant frequency index (ICF) that closely reflects the instantaneous relationship between sympathetic and vagal modulations.