The Effect of Academic Load and Work Conditions on the Sympathoadrenal Function and the Indices of Heart Rhythm Regulation in 17- to 18-Year-Old Girls

The dynamics of the sympathoadrenal function and the specific features of heart rhythm regulation were studied in female students and clothing factory female workers during their adaptation to academic and work conditions. Periods of the strongest functional tension in test systems were found in first-year students: the beginning of an academic year, the end of the first semester, and a period after winter examinations, all characterized by an increase in the central-circuit and sympathetic effects on sinus rhythm, acceleration of the heart rate, activation of sympathoadrenal mechanisms, and a decrease in sympathoadrenal reserves. The comparative analysis allowed us to disclose general trends typical of females of this age group such as the relative maturity of the sympathoadrenal system (SAS) and optimum correlation between autonomic and centralized heart rhythm regulation and to reveal the differences in the character and dynamics of functional shifts caused by a specific effect of academic load and work conditions. The degree of correlation between the indices characteristic of hormonal and mediator SAS mechanisms and the statistical characteristics of heart rhythm was proposed as the criteria for estimating the functional tension of the human body.     

Carbachol-induced Suppression of Contraction Rhythm in Spontaneously Beating Cultured Cardiac Myocytes From Neonatal Rats

Nitric oxide (NO) and reactive oxygen species (ROS) are known to play various functional and pathophysiological roles as an intracellular messenger in the heart. In this study, we investigated whether the increased production of NO and/or ROS was involved in the cholinergic regulation of rhythmic contraction in spontaneously beating cultured cardiac myocytes from neonatal rats. Exposure of cultures to carbachol, an agonist of muscarinic acetylcholine receptors (mAchR), produced a dose-dependent decrease in the beat rate of cultured cardiac myocytes, and such a effect was significantly attenuated by pre-treatment with an NOS inhibitor, as well as an NO scavenger. In addition, exposure to an NO donor (SNAP) also decreased the beat rate dose-dependently. Carbachol- or SNAP-induced suppression of the contraction rhythm was significantly attenuated by co-treatment with 5-hydroxydecanoate (5-HD). In contrast, treatment with diazoxide decreased the beat rate dose-dependently. Carbachol treatment increased the intensity of 2',7'-dichlorodihydrofluorescein fluorescence, suggesting that the production of ROS was enhanced by the treatment. In addition, the carbachol- or diazoxide-induced suppression of contraction rhythm was attenuated by co-treatment with 2-mercaptopropionyl glycine, a scavenger of ROS. The present study has suggested that the mAchR-NO-mitoK ATP -ROS pathway is a factor responsible for carbachol-induced suppression of contraction rhythm in cultured cardiac myocytes.     

Spontaneous activity of hippocampal neurons and stimulation rhythm acquisition in young rabbits during learning: age features

Ontogenetic mechanisms of memory formation were studied using an experimental model of conditioned reflex to time, i.e., trace acquisition of a stimulation rhythm by hippocampal CA1 neurons of young (1-4 weeks old) and adult rabbits (5-6 months old). It was found that age-related development of learning ability includes several stages: complete absence of memory traces (6-7 days old), rapid acquisition without consolidation (8-14 days old), and formation of perfect memory (25-30 days old). Both specific and nonspecific changes in spontaneous activity of neurons were observed. Changes in the rate of discharges related to rhythmic stimulation were accompanied by changes in spontaneous activity. With the development of an animal, spike activity increased in parallel with improving of the functional properties of neurons, their structural organization, formation of the afferent contacts in the hippocampus completed after a period of three weeks from birth, and formation of metabolic processes, modulatory systems, and traffic function of hippocampal neurons. A capability for plastic reorganization is of great importance for adaptation mechanisms and conditioned behavior of a developing animal in accordance with structural maturation and development of the functional regulation of neuronal reactivity in the hippocampus.     

Nonstationary Heart Rate Variability in Respiratory Tests

A new method was proposed for processing a nonstationary heart rate by using frequency-modulated signals rather than amplitude-modulated signals equally spaced over several points of time as in the conventional method. A frequency-modulated signal is a set of identical Gaussian peaks that coincide with the true time points of heart beats. A continuous wavelet transform was used to quantitatively describe the heart rhythm signal. A test with controlled breathing was performed as an example and included three consecutive stages: rest, rhythmic breathing at a specified frequency, and exhalation. Tachograms recorded during the breath test was found to be a nonstationary signal with the alternation of peaks of different spectral ranges. A system of quantitative parameters was developed to describe the dynamics of changes in the spectral properties of the tachogram in transitional areas. A static clustering by the effect of the respiratory test and a dynamic clustering in order to identify the time points when the autonomic nervous system is stressed were performed for all subjects. The article discusses the prospects of using the method as a means to analyze the transient effects in various functional tests and as biofeedback that would help to change the heart rhythm.     

Heart rate and extrasystolic arrhythmias in active subjects aged over 90. A chronobiological study

We analyzed the circadian rhythm of heart rate (HR), of simple atrial premature beats (APB) and of simple ventricular premature beats (VPB) in very old subjects undergoing dynamic ECG for 24 h. The 18 subjects under study (11 women and 7 men) were aged 90 or more (mean +/- SD 92.3 +/- 2.3, range 90-98), did not complain of acute cardiac pathologies, were not taking any medication and were synchronized as to time schedules. The mean duration of DECG recording was of 23 h and 54 min. The collection of data concerning the hourly mean of HR (6 ten-sec samples taken every 10 min) and of the number/hour of APB and VPB was carried out manually. A significant rhythm (single cosinor) was detected for heart rate in 14 subjects out of 18 and in the group (population cosinor); it was also detected for APB (9 subjects out of 15) and for VPB (5 subjects out of 15) also by the single cosinor. It was not detected for the group (population cosinor). No significant correlations, either direct or inverted, were revealed between HR and premature beats. We demonstrate therefore that, even in very old subjects, the circadian rhythm of HR still exists as in younger subjects.     

Additional memory load causes changes in induced EEG beta-rhythm in experiments with a visual set formed to facial expression

Subjects were divided into two equal groups 35 healthy subjects each. Formation of the visual set to facial emotion recognition was supplemented with two types of additional task: either visuospatial (to find a target stimulus among others) or verbal (to tell a word from a pseudoword). The results of the experiments were compared to those obtained in similar experiments without the memory load. Changes in the EEG beta rhythm during visual set forming and testing were studied. The EEG was analyzed by wavelet transformation. Changes in the mean level, maximum and latency of the maximum of wavelet coefficient were rated at different stages of the experiment. All these characteristics for the beta rhythm were higher in experiments with both types of additional memory load as compared to those without the memory load.     

Thyroid effect on brain activity in adolescents during heart rhythm biofeedback session

Types of neurophysiologic and thyroid condition in 15-17-year old adolescents were studied for the purpose of heart rhythm biofeedback session effect by heart rhythm variability parameters. Changes of heart rhythm vegetative regulation activity modulate functional capacities of central vegetative regulation structures. The biofeedback training with heart rhythm variability parameters increases brain bioelectrical activity in different frequency ranges. The thyroid system modulates functional activity of vegetative regulation central structures uppermost at sympathotonic and thyreotropin increasing leads to increase of rhythm maker structure reactivity in brain.     

定量分析丝氨酸/甘氨酸转换影响胃癌细胞增殖的动力学机制

目的 胃癌（GC）严重影响人类的健康生活,研究表明其与丝氨酸/甘氨酸代谢密切相关。丝氨酸/甘氨酸代谢对于肿瘤细胞的增殖能力具有重要影响。本文的研究目的是探究丝氨酸/甘氨酸代谢能够影响胃癌细胞增殖能力的分子机制。方法 本文通过一种基于随机和非梯度系统的势能景观所建立的大型代谢网络动力学建模方法,构建了一个稳定的胃癌细胞代谢动力学模型。基于对模型的调控,定量分析丝氨酸/甘氨酸代谢影响胃癌细胞增殖的动力学机制。对一般代谢网络动力学方程添加随机噪声,通过随机动力学分解得到代谢网络参数空间的李雅普诺夫（Lyapunov）函数。进一步减少与随机波动相关的Lyapunov函数变化,从而得到稳定的代谢网络。结果 在动力学参数不足的情况下,成功构建了胃癌细胞代谢网络的动力学模型。当胞外丝氨酸可用时,模型优先消耗丝氨酸;当甘氨酸生成丝氨酸的速率增加时,模型显著上调生成S-腺苷甲硫氨酸（SAM）和S-腺苷同型半胱氨酸（SAH）的稳态通量。结论 本文证明了胃癌细胞对于丝氨酸的优先摄取以及丝氨酸/甘氨酸转化速率对SAM生成的重要作用,其可能通过调节细胞甲基化进程影响胃癌细胞的增殖能力,为靶向丝氨酸/甘氨酸代谢的癌症治疗提供了新的思路和方向。     

The Observation of an Ultradian Rhythm of Heart Rate in Low Birth Weight Infants

The relationship between ultradian rhythm of heart rate and schedules of body contact or feeding was studied in five low birth weight infants of conceptional ages of 34-36 weeks. The differential contribution of body contact and feeding to the formation of the ultradian rhythm of heart rate was evaluated by applying two different schedules of two- and three-hour periods for feeding with a single schedule of three hours for body contact during an observation period of seven days. A chi-square periodogram was used to calculate the period of ultradian rhythm. As a result, a three-hour ultradian rhythm of heart rates was detected in all subjects, which seems to correspond to either schedule of body contact or of feeding. However, no clear changes in the ultradia n rhythm of heart rate were observed corresponding to changes in feeding schedules. The ultradian rhythm of heart rate seems to correspond more to body contact than to feeding.     

The Observation of an Ultradian Rhythm of Heart Rate in Low Birth Weight Infants

The relationship between ultradian rhythm of heart rate and schedules of body contact or feeding was studied in five low birth weight infants of conceptional ages of 34-36 weeks. The differential contribution of body contact and feeding to the formation of the ultradian rhythm of heart rate was evaluated by applying two different schedules of two- and three-hour periods for feeding with a single schedule of three hours for body contact during an observation period of seven days. A chi-square periodogram was used to calculate the period of ultradian rhythm. As a result, a three-hour ultradian rhythm of heart rates was detected in all subjects, which seems to correspond to either schedule of body contact or of feeding. However, no clear changes in the ultradia n rhythm of heart rate were observed corresponding to changes in feeding schedules. The ultradian rhythm of heart rate seems to correspond more to body contact than to feeding.     

Influence of sound and light on heart rate variability

The effects of acoustic and visual stimuli and their synergistic effects on heart rate variability including gender differences were investigated. Of particular interest was the influence of visual stimulus on heart rate variability during listening to simple sounds of different characters. Twelve male and 12 female university students were selected as subjects. The subjects listened at rest to 7 different figures of sound at loudness levels averaging 60 dB. Beat-to-beat R-R intervals were continuously recorded under the closed-eye condition (CEC) and the open-eye condition (OEC) prior to, during, and immediately after the exposure to acoustic stimuli. Low frequency (LF) power was defined over 0.04-0.15 Hz and high frequency (HF) power over 0.15-0.40 Hz. Cardiac autonomic function was estimated by plotting LF/HF in standard measure against HF in standard measure and by plotting LF/HF (%) against HF (%), accompanied by a demarcated central area. Values of LF/HF tended to be smaller under CEC than under OEC. Values of HF while listening to a 110 Hz sine wave under CEC were significantly greater than values for 880 Hz and 3520 Hz sine waves, or for 110 Hz or 880 Hz sawtooth waves, under OEC. Under CEC, values of HF for 7 figures of sound were greater in females than in males. The value of HF of sine wave for 110 Hz under CEC and OEC was significantly greater than that for white noise under the OEC. The results suggest that the cardiac parasympathetic nervous activity during auditory excitation increases with elimination of visual stimuli and tends to be greater in females than in males.     

15N]glycine metabolism in normal and cirrhotic subjects

Following a single oral dose of 10 mg/kg of [15N]glycine, plasma [15N]glycine kinetics and urinary 15N excretion were measured in 12 cirrhosis patients and in 6 control subjects. Cirrhosis patients were divided into two groups of 6 patients with and without a history of hepatic encephalopathy designated as group II and group I, respectively. Thirty minutes after oral administration of labeled glycine, the plasma concentration of [15N]glycine was significantly higher in both cirrhosis groups than that in the control group (P less than 0.05 and P less than 0.01). The elimination constant of plasma [15N]glycine slightly decreased in group II, but not significantly. Urinary 15N excretion did not differ among the three groups, but the rate of urinary ammonia 15N in urinary 15N was significantly increased in group II (P less than 0.05). The whole-body protein flux did not differ among the three groups, but whole-body protein breakdown was significantly increased in group II cirrhosis patients (P less than 0.05). These findings indicated that the kinetics of glycine were substantially altered in severe cirrhosis patients. Because hepatic uptake and oxidation of glycine was well maintained even in group II, increased endogenous protein breakdown seemed to be responsible for hyperglycinemia and also for the negative nitrogen balance seen in this group.     

Heart Rate Responses to Autonomic Challenges in Obstructive Sleep Apnea

Obstructive sleep apnea (OSA) is accompanied by structural alterations and dysfunction in central autonomic regulatory regions, which may impair dynamic and static cardiovascular regulation, and contribute to other syndrome pathologies. Characterizing cardiovascular responses to autonomic challenges may provide insights into central nervous system impairments, including contributions by sex, since structural alterations are enhanced in OSA females over males. The objective was to assess heart rate responses in OSA versus healthy control subjects to autonomic challenges, and, separately, characterize female and male patterns. We studied 94 subjects, including 37 newly-diagnosed, untreated OSA patients (6 female, age mean±std: 52.1±8.1 years; 31 male aged 54.3±8.4 years), and 57 healthy control subjects (20 female, 50.5±8.1 years; 37 male, 45.6±9.2 years). We measured instantaneous heart rate with pulse oximetry during cold pressor, hand grip, and Valsalva maneuver challenges. All challenges elicited significant heart rate differences between OSA and control groups during and after challenges (repeated measures ANOVA, p<0.05). In post-hoc analyses, OSA females showed greater impairments than OSA males, which included: for cold pressor, lower initial increase (OSA vs. control: 9.5 vs. 7.3 bpm in females, 7.6 vs. 3.7 bpm in males), OSA delay to initial peak (2.5 s females/0.9 s males), slower mid-challenge rate-of-increase (OSA vs. control: −0.11 vs. 0.09 bpm/s in females, 0.03 vs. 0.06 bpm/s in males); for hand grip, lower initial peak (OSA vs. control: 2.6 vs. 4.6 bpm in females, 5.3 vs. 6.0 bpm in males); for Valsalva maneuver, lower Valsalva ratio (OSA vs. control: 1.14 vs. 1.30 in females, 1.29 vs. 1.34 in males), and OSA delay during phase II (0.68 s females/1.31 s males). Heart rate responses showed lower amplitude, delayed onset, and slower rate changes in OSA patients over healthy controls, and impairments may be more pronounced in females. The dysfunctions may reflect central injury in the syndrome, and suggest autonomic deficiencies that may contribute to further tissue and functional pathologies.     

Rapid steroid influences on visually guided sexual behavior in male goldfish

The ability of steroid hormones to rapidly influence cell physiology through nongenomic mechanisms raises the possibility that these molecules may play a role in the dynamic regulation of social behavior, particularly in species in which social stimuli can rapidly influence circulating steroid levels. We therefore tested if testosterone (T), which increases in male goldfish in response to sexual stimuli, can rapidly influence approach responses towards females. Injections of T stimulated approach responses towards the visual cues of females 30–45 min after the injection but did not stimulate approach responses towards stimulus males or affect general activity, indicating that the effect is stimulus-specific and not a secondary consequence of increased arousal. Estradiol produced the same effect 30–45 min and even 10–25 min after administration, and treatment with the aromatase inhibitor fadrozole blocked exogenous T's behavioral effect, indicating that T's rapid stimulation of visual approach responses depends on aromatization. We suggest that T surges induced by sexual stimuli, including preovulatory pheromones, rapidly prime males to mate by increasing sensitivity within visual pathways that guide approach responses towards females and/or by increasing the motivation to approach potential mates through actions within traditional limbic circuits.     

Circadian Rhythm of Blood Pressure and Heart Rate in Cardiopathic Patients Before and After Heart Transplantation

The aim of this study was to investigate the natural history of the circadian rhythm of blood pressure (BP) and heart rate (HR) in 10 patients with heart failure (class IV of the New York Heart Association), who underwent heart transplantation because of primary congestive cardiomyopathy. The control group was 10 age-matched clinically healthy subjects. The BP and HR monitor-ings were performed before and after transplantation. Preoperatively, analysis of variance and cosinor methods validated the occurrence of a statistically significant BP and HR circadian rhythm in cardiopathic patients. Over the 4 days after surgery, both the cosinor method and serial section analysis were unable to validate a 24-h periodicity for BP and HR in patients with heart transplants. Six months after surgery, the BP and HR circadian rhythm was not detected as well. One year after transplantation. the BP and HR circadian rhythm was statistically validated. The recovery of the BP and HR circadian rhythm 1 year after heart transplantation can be regarded as a clinical sign of a reacquired susceptibility to neurovegetative chronoregulation.     

Essential Role of the m2R-RGS6-IKACh Pathway in Controlling Intrinsic Heart Rate Variability

Normal heart function requires generation of a regular rhythm by sinoatrial pacemaker cells and the alteration of this spontaneous heart rate by the autonomic input to match physiological demand. However, the molecular mechanisms that ensure consistent periodicity of cardiac contractions and fine tuning of this process by autonomic system are not completely understood.Here we examined the contribution of the m₂R-I_KACh intracellular signaling pathway, which mediates the negative chronotropic effect of parasympathetic stimulation, to the regulation of the cardiac pacemaking rhythm. Using isolated heart preparations and single-cell recordings we show that the m₂R-I_KACh signaling pathway controls the excitability and firing pattern of the sinoatrial cardiomyocytes and determines variability of cardiac rhythm in a manner independent from the autonomic input. Ablation of the major regulator of this pathway, Rgs6, in mice results in irregular cardiac rhythmicity and increases susceptibility to atrial fibrillation. We further identify several human subjects with variants in the RGS6 gene and show that the loss of function in RGS6 correlates with increased heart rate variability. These findings identify the essential role of the m₂R-I_KACh signaling pathway in the regulation of cardiac sinus rhythm and implicate RGS6 in arrhythmia pathogenesis.     

5-methoxypsoralen: Effect on the noradrenaline circadian rhythm of sleep-deprived subjects

5-methoxypsoralen (5-MOP), a serotonin analogue, stimulates the secretion of melatonin, which plays an important role in circadian rhythm regulation. Melatonin production is essentially controlled by noradrenaline (NA). To investigate the effect of 5-MOP on the 24 hr NA rhythm, hourly plasma NA concentrations measured over 24 hr in 7 healthy young subjects who took 40 mg 5-MOP orally at 21:00 hr the evening before were compared with values obtained in drug-free subjects. All subjects were sleep-deprived and under conditions in which sympathetic nervous system activation was repeated every hour over 24 hr. In both series of patients, a significant difference was observed between mean morning values and mean night values, reflecting persistence of a circadian rhythm. In subjects given 5-MOP, a significant difference was also observed between mean afternoon values and mean night values. However, MANOVA analysis failed to find any difference between the two series of subjects. Acute administration of 5-MOP thus had no significant effect on the NA circadian rhythm under our study conditions.     

Adaptive cardiac responses to local muscular work in children and adults with visual impairment

Preschool children and adults with visual impairments and healthy subjects were examined at rest and after local muscular efforts with the use of a hand dynamometer. In contrast to healthy children, a retarded development of the structure of the cardiac rhythm was found in children with visual impairments. These children, like adults with similar impairments, displayed a high degree of strain of the central mechanisms of cardiac regulation.     

Dynamic aspects of amino acid metabolism in alloxan-induced diabetes and insulin-treated rabbits: in vivo studies with 15N and gas chromatography-mass spectrometry

The present study was designed to determine the effect of alloxan-induced diabetes in rabbits on L-[15N]alanine and [15N]glycine kinetic parameters. This process was measured by single-dose administration of 15N-labeled amino acids to postabsorptive control rabbits and alloxan-induced diabetics and insulin-treated diabetic rabbits. Gas chromatography-mass spectrometry was used to determine the 15N enrichment of plasma glycine and alanine. Glycine and alanine pools and turnover rate constants were estimated from isotope enrichment time decay curves. The data from the present study indicate that plasma glycine and alanine turnover rate constants increased by 25-50% after alloxan administration but pool sizes showed only little changes, resulting in highly significant increases in fluxes and metabolic clearance rates of both alanine and glycine following alloxan administration; single-dose crystalline insulin or protamine zinc insulin treatment failed to restore the turnover rate constants of glycine or alanine toward control values and caused a depletion of 50% in glycine pool size; 7 days prolonged treatment with protamine zinc insulin restored alanine and glycine fluxes and metabolic clearance rates towards control postabsorptive values; and the reduction in flux values following insulin treatment is consistent with the reduction in the plasma glucose levels in rabbits. The data suggest that the regulatory mechanisms for uptake and metabolism of circulating glycogenic amino acids no longer are operative as a consequence of insulin deficiency following alloxan administration. Exogenous insulin restored the activity of the regulatory mechanism toward the postabsorptive control state.     

Significance of cardiac cannabinoid receptors in regulation of cardiac rhythm,myocardial contractility,and electrophysiologic processes in heart

Intravenous administration of cannabinoid (CB) receptor agonists (HU-210, 0.1 mg/kg; ACPA, 0.125 mg/kg; methanandamide, 2.5 mg/kg; and anandamide, 2.5 mg/kg) induced bradycardia in chloralose-anesthetized rats irrespective of the solubilization method. Methanandamide, HU-210, and ACPA had no effect on the electrophysiological activity of the heart, while anandamide increased the duration of the QRS complex. The negative chronotropic effect of HU-210 was due to CB1 receptor activation since it was not observed after CB1 receptor blockade by SR141716A (1 mg/kg intravenously) but was present after pretreatment with CB2 receptor antagonist SR144528 (1 mg/kg intravenously). CB receptor antagonists SR141716A and SR144528 had no effect on cardiac rhythm or ECG indices. Hence, in the intact heart, endogenous CB receptor agonists are not involved in the regulation of cardiac rhythm and electrophysiological processes. The chronotropic effect of CBs was independent of the autonomic nervous system because it remained significant after autonomic ganglion blockade by hexamethonium (1 mg/kg intravenously). CB receptor activation by HU-210 (0.1 and 1 μM) in vitro decreased the rate and force of isolated heart contractions, the rates of contraction and relaxation, and end diastolic pressure. The negative chronotropic effect of HU-210 was less pronounced in vitro than in vivo. The maximum inotropic effect of HU-210 was reached at the concentration of 0.1 μM.