Participation of Modulating Rhythms of the Decasecond Range in Intersystem Correlation Interactions in Early Rat Ontogeny.

On newborn non-narcotized 1-day-old (P1) and 16-day-old (P16) rats, a detailed analysis of intersystem somatovisceral interactions (ISI) mediated by decasecond (D1, 5-50 sec) range modulating rhythms was performed. Correlation interactions of the main body systems - cardiovascular, respiratory and somatomotor systems in norm and under conditions of changes in the level of cholinergic regulation were studied. Spectral correlation analysis was used to determine the participation of D1 range modulating rhythms in ISI. It was found that at P1, D1 range rhythms do not play a significant role in integrative processes. In P16 the activation of cholinergic structures, caused by the introduction of the acetylcholinesterase inhibitor physostigmine (eserine) leads to significant disturbances in the degree of correlation in the D1 range. Blockade of muscarinic and nicotinic cholinoreceptors does not alter the degree of correlation of systemic pairs in the slow-wave region (D1-low, 8-50 sec) of the D1 range. Under the influence on the cholinoreactive structures, the most significant changes in the degree of correlation in the ISI affect the somatorespiratory systemic pair. The results obtained indicate that the representation of the slow-wave components of D1 range modulating rhythms involved in the ISI increase during the first weeks of postnatal ontogeny. Changes in the level of cholinergic activation do not directly influence on ISI mediated by D1-low sub-band rhythms.

Dose-Dependent Heart Rhythm Disturbance Occurring in Response to the Activation of Choline-Reactive Structures in Early Rat Ontogeny.

The effect of dose-dependent activation of cholinoreactive structures on the severity of sinus bradycardia occurring in some intact newborn rats during the first weeks after birth was analyzed in non-narcotized one-day-old (P1) and 16-day-old (P16) rats. The parameters of low-amplitude bradycardic oscillations of heart rhythm in norm and after administration of the acetylcholinesterase inhibitor physostigmine (eserine) in different doses (1/100, 1/10, and 3/4LD50) to rats were studied. The maximum increase in the power of low-amplitude brady-cardic oscillations was achieved during moderate activation of cholinoreactive structures after injection of eserine in a dose of 1/10LD50. Further increase in acetylcholine level led to disappearance of the sinus rhythm and development of pathological bradycardia. The data obtained indicate the immaturity of the mechanisms of heart rhythm regulation in rats immediately after birth. During activation of cholinoreactive structures, the severity of bradycardia oscillations increases exponentially at P1 and has an inverse exponential character at P16, which indicates a high risk of cardiac rhythmogenesis disorders and dysrhythmia development in newborn rats under conditions of excessive enhancement of cholinergic activation.

Changes in Activities of Somatovisceral Systems in Newborn Rats under Conditions of Nicotinic Cholinoreceptor Blockage and Activation of Cholinoreactive Structures.

Relationship between the residual effects of disorders in the cholinergic system and the activities of the cardiac, respiratory, and somatomotor systems of 1- and 16-day-old rats were studied. Experiments were carried out on intact conscious rats before and after drug injection (nicotinic cholinoreceptor blocker benzohexonium). In order to increase the level of cholinoreactive structure activation, acetylcholinesterase inhibition by eserine was carried out. Injection of benzohexonium caused rarefaction of HR, respiration rate, and a decrease of motor activity parameters in rats of both age groups. Injection of eserine after cholinolytic premedication led to further rarefaction of the respiration rate and HR. The reaction of the somatosensory system to changed level of cholinoreactive structure activation was age-specific. Motor activity increased in 1-day-old rats and was depressed significantly in 16-day-old ones.

Heart Rhythm Disturbances Caused by Injection of Cholinesterase Inhibitor Physostigmine to Rats during the Early Ontogeny.

Parameters of cardiac activity after administration of the cholinesterase inhibitor physostigmine were analyzed in newborn rats and on day 16 of postnatal development. The type of cardiovascular response to acetylcholine excess in newborns and 16-day-old rats were similar, but they significantly differed by the magnitude, which suggests that that maturation of cholinergic structures involved in the regulation of cardiac activity is completed during the early postnatal ontogeny.

[CHANGE OF CHARACTER OF INTERSYSTEMIC INTERACTIONS IN NEWBORN RAT PUPS UNDER CONDITIONS OF A DECREASE OF MOTOR ACTIVITY].

Interaction of slow-wave.rhythmic components of cardiac, respiratory.and motor activity was investigated in newborn rat pups on the first day after birth under normal conditions and after pharmacological depression of spontaneous periodic motor activity (SPMA) produced by injecting myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) dosages. The data obtained allow to infer that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of about-one- and many-minute ranges whereas the rhythms of decasecond range do not play a significant role in integrative processes. Injection of miocuran at a dose causing no muscle relaxation and no inhibition of motor activity produces changes of the cardiac and respiratory rhythms as well as a transitory decrease of the magnitude of coordinate relations mediated by the rhythms of about-one- and many-minute ranges. The consequences of muscle relaxant injection were found to be more significant for intersystemic interactions with participation of the respiratory system. An increase of the dosage and, correspondingly, the total inhibition of SPMA is accompanied by reduction of the slow-wave components from the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more expressed in intact rat pups, are reduced in the about-one- and many-minute ranges of modulation whereas in the decasecond range of modulation they are slightly increased. Key words: early ontogenesis, intersystemic interactions, cardiac rhythm, respiration, motor activity, myocuran (myanesin).

[MODIFICATION OF URINE PROTEOME IN HEALTHY HUMAN DURING 21-DAY BED REST].

Mass spectromy-based proteomics was employed to analyze urine from 8 normal volunteers for a 21-day bedrest study (BR). The analysis included trypsinolysis in solution prior to liquid chromatography and tandem mass spectrometry (LC-MS/MS), and spectra processing using the bioinformatics tools. Relying on 221 IPI-indices with Score from 24 to 1700, 169 different proteins were identified. Molecular functions, biological processes and cell components as the loci of certain protein functioning were determined with the help of UniProt-GOA. Associative interactions networks were constructed using BiNGO. There were 14 proteins identified that are functional in the cardiovascular system mostly. They were annotated and -dynamics of their occurrence throughout the experiment was considered. Grounding on the biological functions of these proteins, an assumption of eligible activation of different biological processes during BR was made.

[Change of character of intersystemic interactions in newborn rat pups under conditions of a decrease of central influences (urethane anesthesia)].

On newborn rat pups, for the first day after birth, there was studied the character of mutual influences between the slow-wave rhythmical components of the cardiac, respiratory, and motor activities reflecting interactions between the main functional systems of the developing organism. The study was carried out in norm and after pharmacological depression of the spontaneous periodical motor activity (SPMA) performed by narcotization of rat pups with urethane at low (0.5 g/kg, i/p) and maximal (1 g/kg, i/p) doses. Based on the complex of our obtained data, it is possible to conclude that after birth in rat pups the intersystemic interactions are realized mainly by the slow-wave oscillations of the near- and manyminute diapason. The correlational interactions mediated by rhythms of the decasecond diapason do not play essential role in integrative processes. Injection to the animals of urethane producing selective suppression of reaction of consciousness, but not affecting activating influences of reticular formation on cerebral cortex does not cause marked changes of autonomous parameters, but modulates structure and expression of spontaneous periodical motor activity. There occurs an essential decrease of mutual influences between motor and cardiovascular systems. In the case of preservation of motor activity bursts, a tendency for enhancement of correlational relations between the modulating rhythms of motor and somatomotor systems is observed. The cardiorespiratory interactions, more pronounced in intact rat pups in the near- and many-minute modulation diapason, under conditions of urethane, somewhat decrease, whereas the rhythmical components of the decasecond diapason--are weakly enhanced.

[Cardiac, respiratory, and motor activity in norm and after activation of catecholaminergic systems in newborn rat pups].

Study of parameters of the cardiac, respiratory, and motor activity (MA) was carried out on newborn rat pups for the first day after birth (P0) and at the 14th day of postnatal development (P14) after change of the level of activity of catecholaminergic systems. The animals were administered with L-DOPA (25-100 mg/kg) and the indirect adrenomimetic isoamine (3 and 10 mg/kg). Additionally there were studied effects of L-DOPA and isoamine after blockade of D1 and D2 dopamine receptors (antagonists SCH-23390 and sulpiride). The L-DOPA administration produced a dose-dependent MA enhancement with its possible transition into the uninterrupted activity. In P0 the release of monoamines was accompanied by development of weak bradycardia. There was noted a tendency for acceleration of respiration at administration of the low dose both of L-DOPA and of isoamine and for its retardation at high doses. In P14 the L-DOPA administration was accompanied by retardation of the heart rate (HR) by 8 % and by acceleration of respiratory rate by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of respiratory rate (RR) by 8% at the low dose and by 21% at the high dose of the agent. At the blockade of D1 receptors, RR remained close to the background values, while at the blockade of D2 - decreased insignificantly. Blockade of D1 and D2 receptors did not cause significant HR changes. Analysis of the HR variability has shown that both after L-DOPA administration and at blockade of dopamine receptors no unidirectional reaction was observed: in 80 % of rat pups the portion of nerve mechanisms of HR regulation increased, while in the rest--of sympathetic and humoral factors at a decrease of parasympathetic effects. In all rat pups the isoamine administration was accompanied by a shift of the specter power into the higher frequency area; in 60% of animals there were enhanced sympathetic influences. In P14 in rat pups after administration both of L-DOPA and of isoamine, the symphathetic nervous influences were predominant. Thus, in P0 both at release of endogenous catecholamines and at their excessive concentration in rat pups there occurs a qualitative change of character of the catecholaminergic influences on functional activity of excitable structures, especially of those connected with regulation of respiration.

[Effect of change in levels of motor activity and innervation on basic and secondary rhythms of rat heart rate and respiration in ontogenesis].

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneos motor activity were studied on offspring of white rats from newborn to 3-week age at transition from the state of active wakefulness to narcosis as well as under conditions of blockade of M-cholinoreceptors with atropine. It is shown that the endogenous rhythmical activity can be regulated not only by a change in frequency of basic rhythms, but also by action on all parameters and properties of their rhythmical variations and secondary rhythms. The changes in power of the heart secondary rhythms exceed considerably the frequency oscillations of basic rhythms during blockade of cholinergic innervation or a change in the motor activity level that affects both the basic rhythm circulation and respiration and their variations--secondary rhythms. The atropine blockade of M-cholinoreceptors at the studied ages changes the heart beating rhythm within the limits of 10% of bradicardia in newborns to tachycardia in the 3-week old animals. At the same time, power of the cardiac rhythm secondary oscillations changes several times. These data indicate that the cholinergic mechanisms play the key role in formation of the secondary rhythms and their correlation with motor activity.

[Secondary rhythms of automatically functioning systems].

In wakeful rats at the age from newborn to 3 weeks there were studied interrelations of rhythmical fluctuations of heart rate, respiration rate, and periodic spontaneous motor activity. In all studied systems, these fluctuations are coordinated and occur in several frequency diapasons. Frequencies in the periminute diapason (the period from 30 to 90 s) are the most constant and do not change with age. Regular fluctuations are the most stable in newborns. Bursts of motor activity usually are irregular, but episodically the distinct periminute rhythm is traced. Studies of the character of interaction of the heart activity, respiration, and periodic somatomotor excitation allow stating that the main coordination pathway of spontaneous autorhythmical functions in early postnatal ontogenesis is formation of secondary rhythms. Possible pathway of formation of the secondary rhythms are considered.

[Action of novocain on cardiac and somatomotor autorhythmical functions in early postnatal ontogenesis in rats].

In conscious rat pups aged 2-3, 10-11, and 22-23 postnatal days, it has been shown that intraperitoneal administration of 0.5 % novocain at a dose of 25 mg/kg body mass leads to phasic changes of the level of spontaneous periodic motor activity--from increased at once after the administration to depression and subsequent restoration. They are accompanied by the cardiac rhythm fluctuations that change with age their direction on the background of an increased motor activity from brady--to tachycardia. All the changes are the most pronounced in newborns. At comparison of the results with the afferent impulsation level fluctuations recorded under the same conditions in the peripheral vagus segment, it is suggested that the revealed reactions are associated with changes of the interoceptive afferentation flow. The conclusion is made that at early stages of ontogenesis, interoception plays an important role in regulation of autorhythmical functions and that this role decreases with age.

[The effect of L-DOPA on the motor activity of mouse fetuses]. / Vliianie L-DOFA na dvigatel'nuiu aktivnost' plodov myshei.

In the white mice fetus 17-20 days old the motive activity organization is often represented by the single oscillations comprised 63% of the total quantity of motions. 36% of them group into the series, and the generalized activity registered as continuous oscillation complexes is observed only in the single cases. When female is injected subcutaneously with L-DOPA (100 mg/kg) the increase in series oscillations grouping as well as increase in quantity of the continuous activity complexes takes place. It is come to the conclusion that L-DOPA use leads to the revealing for the motive activity features which are characteristics for the older age.