Baroreflex dysfunction in rats submitted to protein restriction

Earlier studies from the authors' laboratory showed that malnourishment induces alterations in the cardiovascular homeostasis increasing the basal mean arterial pressure and heart rate. In this study, the authors evaluated whether the sympathetic and parasympathetic efferent activities contribute to changes in the cardiovascular homeostasis through altered modulation of the arterial baroreflex of malnourished rats. After weaning, male Fischer rats were given 15% (Normal Protein--NP) or 6% (Low Protein--LP) protein diet for 35 d. The baroreflex gain and latency were evaluated before and after selective autonomic blockades in control and malnourished rats. It was observed that malnourishment affected the baroreflex gain in response to activation and deactivation of the arterial baroreflex. Moreover, malnourished rats showed increased baroreflex latency as compared to that of control rats. Regarding the autonomic efferent activity directed to the heart, the data showed increased sympathetic and decreased parasympathetic efferent activities in malnourished rats, and such alterations could be related to the observed changes in the arterial baroreflex gain as well as in the basal mean arterial pressure and heart rate.     

Effect of head-down-tilt bed rest and hypovolemia on dynamic regulation of heart rate and blood pressure

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

High-Pass Filter Characteristics of the Baroreflex – A Comparison of Frequency Domain and Pharmacological Methods

Pharmacological methods to assess baroreflex sensitivity evoke supra-physiological blood pressure changes whereas computational methods use spontaneous fluctuations of blood pressure. The relationships among the different baroreflex assessment methods are still not fully understood. Although strong advocates for each technique exist, the differences between these methods need further clarification. Understanding the differences between pharmacological and spontaneous baroreflex methods could provide important insight into the baroreflex physiology. We compared the modified Oxford baroreflex gain and the transfer function modulus between spontaneous RR interval and blood pressure fluctuations in 18 healthy subjects (age: 39±10 yrs., BMI: 26±4.9). The transfer function was calculated over the low-frequency range of the RR interval and systolic blood pressure oscillations during random-frequency paced breathing. The average modified Oxford baroreflex gain was lower than the average transfer function modulus (15.7±9.2 ms/mmHg vs. 19.4±10.5 ms/mmHg, P<0.05). The difference between the two baroreflex measures within the individual subjects comprised a systematic difference (relative mean difference: 20.7%) and a random variance (typical error: 3.9 ms/mmHg). The transfer function modulus gradually increased with the frequency within the low-frequency range (LF), on average from 10.4±7.3 ms/mmHg to 21.2±9.8 ms/mmHg across subjects. Narrowing the zone of interest within the LF band produced a decrease in both the systematic difference (relative mean difference: 0.5%) and the random variance (typical error: 2.1 ms/mmHg) between the modified Oxford gain and the transfer function modulus. Our data suggest that the frequency dependent increase in low-frequency transfer function modulus between RR interval and blood pressure fluctuations contributes to both the systematic difference (bias) and the random variance (error) between the pharmacological and transfer function baroreflex measures. This finding suggests that both methodological and physiological factors underlie the observed disagreement between the pharmacological and the transfer function method. Thus both baroreflex measures contribute complementary information and can be considered valid methods for baroreflex sensitivity assessment.     

A delay recruitment model of the cardiovascular control system

We develop a nonlinear delay-differential equation for the human cardiovascular control system, and use it to explore blood pressure and heart rate variability under short-term baroreflex control. The model incorporates an intrinsically stable heart rate in the absence of nervous control, and allows us to compare the baroreflex influence on heart rate and peripheral resistance. Analytical simplifications of the model allow a general investigation of the rôles played by gain and delay, and the effects of ageing.     

Heart rate variability following coronary artery bypass graft surgery as a function of recovery time, posture, and exercise

This study examined the claim made by Niemela et al. (1992) that the decline in heart rate variability after coronary artery bypass graft surgery is irreversible. We tested six women and 16 men six and 12 weeks postoperative in three postures: in the supine position, in the standing position, and during low-intensity steady-state exercise. Beat-by-beat arterial blood pressure and electrocardiographic R-R interval data were collected continuously for 10 min in each condition. R-R interval data were analyzed with spectral analysis; baroreflex data were analyzed using the sequence method. Our results show that the indices of parasympathetic modulation improved over time, as seen by an increased spontaneous baroreflex sensitivity and parasympathetic indicator, that both indices were affected by posture, and that spontaneous baroreflex sensitivity was also affected by low-intensity exercise. The effects of posture are consistent with attenuated responses of healthy older subjects to orthostatic stress. Similarly, the effects of low-intensity exercise are consistent with findings in healthy subjects. We found that spontaneous baroreflex sensitivity declined during exercise, whereas, in healthy subjects, this is maintained during low-intensity steady-state exercise. Our results of significant functional recovery between six and 12 weeks postoperative suggest that at least some of the autonomic dysfunction following surgery is temporary. Previously, no such duration of study has lasted longer than four or six weeks following cardiac surgery, which may not have been long enough to show significant functional restoration in heart rate variability.     

Dose-response relationship of endurance training for autonomic circulatory control in healthy seniors.

Aging results in marked abnormalities of cardiovascular regulation. Regular exercise can improve many of these age-related abnormalities. However, it remains unclear how much exercise is optimal to achieve this improvement or whether the elderly can ever improve autonomic control by exercise training to a degree similar to that observed in healthy young individuals. Ten healthy sedentary seniors [71 +/- 3 (SD) yr] trained for 12 mo; training involved progressive increases in volume and intensity. Static hemodynamics were measured, and R-wave-R-wave interval (RRI), beat-to-beat blood pressure (BP) variability, and transfer function gain between systolic BP and RRI were calculated at baseline and every 3 mo during training. Data were compared with those obtained in 12 Masters athletes (68 +/- 3 yr) and 11 healthy sedentary young individuals (29 +/- 6 yr) at baseline. Additionally, the adaptation of these variables after completion of identical training loads was compared between the seniors and the young. Indexes of RRI variability and baroreflex gain were decreased in the sedentary seniors but preserved in the Masters athletes compared with the young at baseline. With training in the seniors, baroreflex gain and resting BP showed a peak adaptation after moderate doses of training following 3-6 mo. Indexes of RRI variability continued to improve with increasing doses of training and increased to the same magnitude as the young at baseline after heavy doses of training for 12 mo; however, baroreflex gain never achieved values equivalent to the young at baseline, even after a year of training. The magnitude of the adaptation of these variables to identical training loads was similar (no interaction effects of age x training) between the seniors and the young. Thus RRI variability in seniors improves with increasing "dose" of exercise over 1 yr of training. In contrast, more moderate doses of training for 3-6 mo may optimally improve baroreflex sensitivity, associated with a modest hypotensive effect; however, higher doses of training do not lead to greater enhancement of these changes. Seniors retain a similar degree of "trainability" as young subjects for cardiac autonomic function to dynamic exercise.     

The state transition mechanism—simply depending on light-on and -off in Spirulina platensis

The state transition in cyanobacteria is a long-discussed topic of how the photosynthetic machine regulates the excitation energy distribution in balance between the two photosystems. In the current work, whether the state transition is realized by “mobile phycobilisome (PBS)” or “energy spillover” has been clearly answered by monitoring the spectral responses of the intact cells of the cyanobacterium Spirulina platensis. Firstly, light-induced state transition depends completely on a movement of PBSs toward PSI or PSII while the redox-induced one on not only the “mobile PBS” but also an “energy spillover”. Secondly, the “energy spillover” is triggered by dissociation of PSI trimers into the monomers which specially occurs under a case from light to dark, while the PSI monomers will re-aggregate into the trimers under a case from dark to light, i.e., the PSI oligomerization is reversibly regulated by light switch on and off. Thirdly, PSI oligomerization is regulated by the local H⁺ concentration on the cytosol side of the thylakoid membranes, which in turn is regulated by light switch on and off. Fourthly, PSI oligomerization change is the only mechanism for the “energy spillover”. Thus, it can be concluded that the “mobile PBS” is a common rule for light-induced state transition while the “energy spillover” is only a special case when dark condition is involved.     

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.     

The birthrate drop in Iran

The recent steep decline in Iran's birthrate poses methodological and interpretive challenges insofar as statistical information on demographic factors cannot satisfactorily establish causalities or delineate processes of change. Our research suggests that this decline rests on the interplay of socio-cultural “idea” variables that augment factors of the developmental paradigm commonly used in population studies. Especially modernist ideas labeled “progress” in Iran have influenced reproductive behavior. Aiming to demonstrate the usefulness of idea-oriented qualitative research for understanding demographic dynamics represented quantitatively in the literature, we contribute to an explanation of a particular case as well as to demographic research methods.     

Autonomic control of the respiratory-hemodynamic system in 8-to 11-year-old children with different baroreflex sensitivities

The efficiency of baroreflex control depends on the baroreflex sensitivity (BRS), which is defined as the ratio of the change in the heart rate (HR) to the change in the blood pressure (BP). The BRS value may be used for assessing the autonomic control of the cardiovascular system and the degree of autonomic dysfunction. Until recently, the baroreflex had not been assessed in a large population of healthy subjects. In this study, the BRS was estimated by the ratio of the low-frequency component of the HR spectrum and the low-frequency component of the rhythm of the systolic BP. For assessing the arterial baroreflex in children, the BRSs for spontaneous and induced baroreflexes were compared. Sex-and age-related differences in BRS were found in 8-to-11-year-old children, and correlations between BRS and some spectral components of HR variability (HRV) and BP rhythm variability were determined. Cluster analysis of the BRS calculated for the spontaneous baroreflex at rest was used to distinguish three clusters of subjects (with high, medium, and low BRSs). These clusters differed in the variability of the basic parameter and size and showed sex-related differences.     

Baroreflex sensitivity during operant blood pressure conditioning

Baroreflex sensitivity was measured in baboons operantly conditioned to increase their diastolic blood pressure in daily, 12-hr sessions, by using the extent of increases in interpulse interval per unit of increase in systolic pressure after intravenous phenylephrine injection as an index of baroreflex sensitivity. Following training, baroreflex sensitivity increases averaging 32% were observed before and after the 12-hr conditioning sessions. During the conditioning sessions, however, consistent diastolic blood pressure elevations averaging 17% (14 mmHg) were accompanied by significant decreases in baroreflex sensitivity averaging 44% relative to the increased before and after sensitivity levels. The results suggest that changes in baroreflex sensitivity participate in operantly conditioned blood pressure changes.     

Characterization and polymorphism of Keratin Associated Protein 1.4 gene in goats

Keratin-associated proteins (KAPs) are among the main structural components of the animal fibers and form semi-rigid matrix wherein the keratin intermediate filaments (KIFs) are embedded. Variation in the KAP genes has been reported to affect the structure of KAPs and hence fiber characteristics. As no information is available on this gene in Capra hircus therefore, present work was undertaken to characterize and explore the different polymorphic variants of KAP1.4 gene at DNA level in different breeds/genetic groups of goats of Kashmir. Cashmere (Changthangi, 30 animals) and non-Cashmere (Bakerwal and Kargil goats, 20 animals each) goats formed the experimental animals for the study. Single strand conformation polymorphism technique was employed for exploring variability at gene level. On exploring the size variability in KAP1.4 gene between Ovine and Caprine, it was concluded that sheep KAP1.4 gene has a deletion of 30 nucleotides. In comparison to published nucleotide sequences of sheep, goat sequences explored are differing at positions 174, 462 and 568 and at these positions “G”, “T” and “T” nucleotides are present in sheep, but are replaced by “A”, “C” and “C” respectively, in goats. By SSC studies, two genotypes were observed in each genetic group and in Bakerwal goats the genotypes were designated as A1A1 (0.40) and A1A2 (0.60) and were formed by two alleles A1 (0.70) andA2 (0.30). The different SSC patterns observed in Kargil goats were designated as B1B1 (0.35) and B1B2 (0.65) genotypes with frequencies of B1 and B2 alleles as 0.675 and 0.325, respectively. Similarly, two genotypes C1C1 (0.60) and C1C2 (0.40) were observed in Changthangi goats and the frequencies of C1 and C2 alleles were 0.80 and 0.20, respectively. These alleles were later confirmed by sequencing. The sequences of these alleles are available in NCBI under Acc. No's. JN012101.1, JN012102.1, JN000317.1, JN000318.1, JQ436929 and JQ627657. It was concluded that all the alleles observed in a breed were unique to the breed. The designated A1 and A2 alleles of Bakerwal goats differ from each other at positions 245 and the nucleotides observed were “C” or “A” and at position 605 of the nucleotide sequence “T” or “C”, were observed. The designated B1 and B2 alleles of Kargil goats differed from each other at positions 224, 374, 375 and 521. The nucleotides observed in two SSC pattern were C→G, A→G, G→A and T→C, respectively. The designated C1 and C2 alleles of Changthangi goats differed from each other at one position 440 with the change of “A”→“C”.     

Une lame de faucille sous la stèle gravée Chalcolithique dite du « Chef de tribu », Vallée des Merveilles, région du Mont Bego, Tende, Alpes-Maritimes

The carved stele known as the “head of the tribe”, attributed to the Chalcolithic, erected at an altitude of 2290 m in the chaos of blocks in the Merveilles torrent in the Mont Bego region at Tende, was removed from its original standing place. Earth extracted from under the stele and sieved yielded a sickle blade in very fine and homogeneous Bedoulian pale biege translucid flint, pressure flaked on a heated core. The blade bears a light polish caused by cereal harvesting. This sickle blade is similar to those widely used in the southern Chassey culture (4300 to 3000 years before our era) but also sometimes in the Campaniform culture, during the ancient and middle Bronze age, like in Murée cave, in the Verdon gorges. The location of the sickle blade at the foot of the carved stele, known as the “head of the tribe”, is not just coincidental. It is highly probable that the blade was intentionally placed beside this rock. It is seemingly during a ritual ceremony that this sickle blade, probably still inserted in a wooden handle, was intentionally placed, in a propitious gesture or as an offering, beside the stele known as the “head of the tribe”.     

Baroreflex sensitivity: mechanisms and measurement

This article is a brief review of baroreflex physiology, the definition and functional meaning of baroreflex sensitivity, and the methods used to measure baroreflex sensitivity. The arterial baroreflex is important for haemodynamic stability and for cardioprotection, and it has convincingly been demonstrated that baroreflex sensitivity, even when assessed with different methods, has a strong prognostic value. Development of new baroreflex assessing procedures is still ongoing, with a focus on increased reliability in difficult measuring circumstances, e.g., in patients with a weak baroreflex and in patients with frequent arrhythmias.     

Impaired cardiac and sympathetic autonomic control in rats differing in acetylcholine receptor sensitivity

Acetylcholine receptors (AChR) are important in premotor and efferent control of autonomic function; however, the extent to which cardiovascular function is affected by genetic variations in AChR sensitivity is unknown. We assessed heart rate variability (HRV) and baroreflex sensitivity (BRS) in rats bred for resistance (FRL) or sensitivity (FSL) to cholinergic agents compared with Sprague-Dawley rats (SD), confirmed by using hypothermic responses evoked by the muscarinic agonist oxotremorine (0.2 mg/kg i.p.) (n > or = 9 rats/group). Arterial pressure, ECG, and splanchnic sympathetic (SNA) and phrenic (PNA) nerve activities were acquired under anesthesia (urethane 1.3 g/kg i.p.). HRV was assessed in time and frequency domains from short-term R-R interval data, and spontaneous heart rate BRS was obtained by using a sequence method at rest and after administration of atropine methylnitrate (mATR, 2 mg/kg i.v.). Heart rate and SNA baroreflex gains were assessed by using conventional pharmacological methods. FRL and FSL were normotensive but displayed elevated heart rates, reduced HRV and HF power, and spontaneous BRS compared with SD. mATR had no effect on these parameters in FRL or FSL, indicating reduced cardiovagal tone. FSL exhibited reduced PNA frequency, longer baroreflex latency, and reduced baroreflex gain of heart rate and SNA compared with FRL and SD, indicating in FSL dual impairment of cardiac and circulatory baroreflexes. These findings show that AChR resistance results in reduced cardiac muscarinic receptor function leading to cardiovagal insufficiency. In contrast, AChR sensitivity results in autonomic and respiratory abnormalities arising from alterations in central muscarinic and or other neurotransmitter receptors.     

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

The purpose of this project was to identify whether dynamic baroreflex regulation of heart rate (HR) is altered during whole body heating. In 14 subjects, dynamic baroreflex regulation of HR was assessed using transfer function analysis. In normothermic and heat-stressed conditions, each subject breathed at a fixed rate (0. 25 Hz) while beat-by-beat HR and systolic blood pressure (SBP) were obtained. Whole body heating significantly increased sublingual temperature, HR, and forearm skin blood flow. Spectral analysis of HR and SBP revealed that the heat stress significantly reduced HR and SBP variability within the high-frequency range (0.2-0.3 Hz), reduced SBP variability within the low-frequency range (0.03-0.15 Hz), and increased the ratio of low- to high-frequency HR variability (all P < 0.01). Transfer function gain analysis showed that the heat stress reduced dynamic baroreflex regulation of HR within the high-frequency range (from 1.04 +/- 0.06 to 0.54 +/- 0.6 beats. min(-1). mmHg(-1); P < 0.001) without significantly affecting the gain in the low-frequency range (P = 0.63). These data suggest that whole body heating reduced high-frequency dynamic baroreflex regulation of HR associated with spontaneous changes in blood pressure. Reduced vagal baroreflex regulation of HR may contribute to reduced orthostatic tolerance known to occur in humans during heat stress.     

Cascade model of ventricular-arterial coupling and arterial-cardiac baroreflex function for cardiovascular variability in humans

Cardiovascular variability reflects autonomic regulation of blood pressure (BP) and heart rate (HR). However, systolic BP (SBP) variability also may be induced by fluctuations in stroke volume through left ventricular end-diastolic pressure (LVEDP) variability via dynamic ventricular-arterial coupling during respiration. We hypothesized that dynamic ventricular-arterial coupling is modulated by changes in left ventricular compliance associated with altered preload and that a cascade control mechanism of ventricular-arterial coupling with arterial-cardiac baroreflex function contributes to the genesis of cardiovascular variability at the respiratory frequency. Seven healthy young subjects underwent 6-min recordings of beat-by-beat LVEDP, SBP, and HR in the supine position with controlled respiration at 0.2 Hz during hyper- and hypovolemia. Spectral and transfer function analysis of these variables was conducted between 0.18 and 0.22 Hz. Dynamic ventricular-arterial coupling gain (Gain LVEDP-SBP) was smaller by 25% (P = 0.009) during hypervolemia than during hypovolemia, whereas arterial-cardiac baroreflex function gain (Gain SBP-HR) was similar. As predicted from a cascade model, a linear relationship between Gain LVEDP-HR and LVEDP-SBP times Gain SBP-HR was identified (R(2) = 0.93, P < 0.001). Gain LVEDP-HR was smaller by 40% (P = 0.04) during hypervolemia than during hypovolemia, leading to a reduction in spectral power of HR variability by 45% (P = 0.08). We conclude that dynamic ventricular-arterial coupling gain is reduced during hypervolemia because of a decrease in left ventricular compliance. A cascade model of ventricular-arterial coupling with the arterial-cardiac baroreflex contributes to the genesis of cardiovascular variability at the respiratory frequency.     

Boosting classifier for predicting protein domain structural class

A novel classifier, the so-called “LogitBoost” classifier, was introduced to predict the structural class of a protein domain according to its amino acid sequence. LogitBoost is featured by introducing a log-likelihood loss function to reduce the sensitivity to noise and outliers, as well as by performing classification via combining many weak classifiers together to build up a very strong and robust classifier. It was demonstrated thru jackknife cross-validation tests that LogitBoost outperformed other classifiers including “support vector machine,” a very powerful classifier widely used in biological literatures. It is anticipated that LogitBoost can also become a useful vehicle in classifying other attributes of proteins according to their sequences, such as subcellular localization and enzyme family class, among many others.     

Hommes et environnements au Paléolithique supérieur en Ukraine continentale et en Crimée : introduction

Research, conducted under the ANR project “Mammouths”, on “the end of the mammoth steppe: Man/Environment relationship during late Pleniglacial in Eastern Europe”, is the subject of several contributions, a part of them is published in this volume, under the heading “Humans and environments during Upper Paleolithic in mainland Ukraine and Crimea”, in the French journal L’anthropologie.