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.

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.

Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities was analyzed in non-narcotized of newborn 1-day-old (P1) and 16-day-old (P16) Wistar rat pups under normal and impaired cholinergic regulation. Functional activity of these three systems is rhythmic, and coordination of their functioning is an important element of the mechanism of adaptive rearrangements under changing factors of the external and internal environment. The acetylcholinesterase inhibitor physostigmine (eserine) was used to increase the level of endogenous acetylcholine and enhance cholinergic effects. To reveal the role of N-cholinoreceptors in intersystemic somatovisceral interactions (ISI), we performed blockade of this receptor type with benzohexonium. Administration of physostigmine leads to the development of a number of pathological reactions and a decrease in the level of ISI in all ranges of modulating rhythms in rats of both ages. ISI in younger rats appear to be more resistant to changes in the level of cholinergic activation. Blockade of N-cholinoreceptors causes inhibition of ISI at P1 and partially to their potentialization at P16. The activation of cholinoreactive structures, which occurred against the background of cholinoreceptors blockade, reduces the pathological effects of physostigmine in animals of both ages, but at the same time leads to an attenuation of ISI. This weakening is more pronounced in 16-day old rats, which may indicate the formation of the definitive level of cholinergic regulation in the first weeks of postnatal ontogenesis.

Interaction of slow-wave rhythmic components of cardiac, respiratoryand motor activities was analyzed in non-narcotized neonatal (P1)and early postnatal (P16) rat pups under normal conditions and afteractivation of cholinoreactive structures. A reversible acetylcholinesterase (AChE)inhibitor physostigmine (eserine) and the M-cholinolytic methacinwere used in the experiments. It was established that in intactP1 rats intersystemic interactions are mainly realized via oscillationswithin the near- and multi-minute ranges. Correlative interactionsbetween the rhythms in the decasecond range that were not involvedin integrative processes in P1 rats increased significantly at P16.In rat pups of both ages, changes in the intensity and pattern ofmotor activity (MA) tended to precede the generation of modulatoryoscillations of the respiratory and heart rates. AChE inhibitionby physostigmine and subsequent activation of cholinoreactive structuresevoked a decrease in the level of intersystemic interactions acrossall ranges of the modulatory rhythms in rats of both ages. The methacin-evokedblockade of peripheral M-cholinoreceptors (M-ChRs) decreased thelevel of interactions mediated by the near- and multi-minute rhythmsat P1 but augmented them at P16. Physostigmine injection at P1 andP16 exerted no significant effect on cardio-somatomotor interactions,with these interactions in P1 rats being maintained by a wider rangeof the modulatory rhythms. The same situation was also observedduring the physostigmine aftereffect period in all interacting systemicpairs. By contrast, after the blockade of peripheral M-ChRs theexisting intersystemic interactions were more difficult to be disruptedin P16 rat pups. The activation of cholinoreactive structures, whichoccurred against the background of M-ChRs blockade, led to disruptthe coordinating interactions in the “MA–respiratory rate” pair.In P1 rats, these functional relationships did not recover, whilein P16 rats they were resumed already during the aftereffect period.The power of modulatory rhythms of activity in the systems studiedhere was not directly related to intersystemic interactions. Changesin intersystemic interactions were due to heterochrony both in thematuration of these functional systems and the involvement of different cholinoreactivestructures in the processes of intersystemic regulation.

Activities of the somatomotor, cardiovascular and respiratory systems were investigated in conditions of impaired cholinergic regulation in rat pups aged 1 and 16 days. Acetylcholinesterase (AChE) inhibition by physostigmine (eserine), which leads to activate cholinoreactive structures, is accompanied by a unidirectional impairment of the cardiac sinus rhythm in newborn and, to a lesser extent, 16-day-old rats. Activation of cholinoreactive structures decreases the rate and regularity of breathing and also alters the pattern and parameters of motor activity. Physostigmine injection potentiates motor activity in 1-day-old and depresses it in 16-day-old rats. The blockade of muscarinic cholinoreceptors in rats of both age groups largely affects functional activity of the cardiovascular system, preventing severe cardiac arrhythmias caused by injection of the AChE inhibitor. It was shown that the formation of the definitive level of cholinergic regulation, including the maturation of the mechanisms underlying reciprocal interactions within the cholinergic system itself, is completed in the early period of rat postnatal ontogenesis. Age-related differences in responses of the somatomotor, cardiovascular and respiratory systems to changes in the level of activation of cholinoreactive structures are associated with these processes.

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.

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.

Interaction of slow-wave rhythmic components of cardiac, respiratory and motor activities 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) induced by injection of myocuran (myanesin) at low (100 mg/pg, i/p) and maximal (235 mg/pg, i/p) doses. The data obtained indicate that in rat pups after birth the intersystemic interactions are realized mainly via slow-wave oscillations of the near-minute or multiminute ranges, whereas the rhythms of the decasecond range do not play a significant role in integrative processes. Injection of myocuran at a dose causing neither muscle relaxation nor inhibition of motor activity induces changes in the cardiac and respiratory rhythms as well as a transitory decrease in the magnitude of coordinating relations mediated by the rhythms of the near-minute and multiminute ranges. The consequences of myorelaxant injection were found to be more significant for intersystemic interactions with the involvement of the respiratory system. The increase in the myocuran dose and, correspondingly, complete inhibition of SPMA is accompanied by the reduction in the slow-wave components of the pattern of cardiac and respiratory rhythms. The cardiorespiratory interactions, more pronounced in intact rat pups, decrease in the near-minute and multiminute modulation ranges and increase insignificantly in the decasecond modulation range.

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.

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 activity levels of dopaminergic and noradrenergic systems. To provide an excessive level of catecholamines, the animals were administered individually with L-DOPA (25–100 mg/kg) and with 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 sulpirid). The L-DOPA administration produced a dose-dependent MA enhancement with its subsequent possible conversion into the continuous generalized activity. At 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 deceleration at high doses. At P14 the L-DOPA administration was accompanied by deceleration of the heart rate (HR) by 8% and by acceleration of respiration rate (RR) by 26%. The isoamine administration produced an insignificant decrease of HR and an increase of 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 receptors it 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 the animals there were enhanced sympathetic effects. At P14 in rat pups after administration both of L-DOPA and of isoamine, the sympathetic nervous effects were predominant. Thus, at 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 effects on functional activity of excitable structures, particularly of those connected with regulation of respiration.

Changes in the heart basic rhythm, its rhythmical variations on periodograms, and level of spontaneous 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 contraction rhythm within the limits of 10% of bradycardia 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.

In wakeful rats at the age from newborn to 3 weeks there were studied interrelations of rhythmical oscillations of heart rate, respiration rate, and periodic spontaneous motor activity. In all studied systems, these oscillations are coordinated and occur in several frequency diapasons. Frequencies in the near-minute diapason (the period from 30 to 90 s) are the most constant and do not change with age. Regular oscillations are the most stable in newborns. Bursts of motor activity usually are irregular, but episodically the distinct near-minute 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 autorhythmic functions in early postnatal ontogenesis is formation of secondary rhythms. Possible ways of formation of the secondary rhythms are considered.

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.

In progeny of Wistar rats aged from birth to 3 week, there was studied participation of sympathetic and parasympathetic mechanisms in regulation of cardiac rhythm and its rhythmic oscillations (secondary cardiac rhythms), whose spectral composition was analyzed using rapid Fourier transformation. Consequences, which changed in the process of development, of blockade of β-adrenoreceptors by propranolol, of α-adrenoreceptors by phentolamine, and of muscarinic cholinoreceptors by atropine as well as of chronic desympathization by guanethidine (isobarine). It was found that due to heterochronia in establishment of functions of sympathetic and parasympathetic nervous systems, reactions to blockade of adreno- and cholinoreceptors for the first 3 weeks of postnatal ontogenesis changed not only quantitatively, but also qualitatively. Blockade of adrenoreceptors in newborn animals leads to an increase of power of the rhythm oscillations in all low-frequency diapasons. The baroreflex function of parasympathetic innervation is well expressed as early as in newborns. Tonic function with respect to frequency of heart rate and power of oscillations in the high-frequency diapason becomes evident only by the 3-week age.

The genesis of secondary rhythms in autorhythmic functional systems is analyzed on the example of the spectra of fluctuations of the heart rate observed within early postnatal ontogenesis of rats (from the moment of birth until three weeks old). We studied the effects of blocking of α-adrenoreceptors with phentolamine (5 mg/kg, i.p.), of β-adrenoreceptors with propranolol (1 mg/kg), and of M cholinoreceptors with atropine (1 mg/kg). We concluded that sympathetic influences stabilize the cardiac rhythm in newborn animals, but from the second postnatal week the effects determining generation of secondary rhythms of cardiac activity begin to be mediated by these receptors. Parasympathetic effects on secondary cardiorhythms mediated by M cholinoreceptors are effective even in newborn rats. In rats older than 7 to 8 days, blocking of α-adrenoreceptors and M cholinoreceptors led to the same result, synchronization of the secondary cardiac rhythms. Disorders in the afferent link of the baroreflex arcs after the blockade of α-adrenoreceptors and cessation of transmission in the efferent link of these arcs after blockade of M cholinoreceptors are considered a probable reason for this phenomenon.

Endogenous periodic oscillations of the heart beat rate are described in rat pups aged 3–4, 7–8, 10–11, 13–14, 21–22 days and 1.5 month after birth. These oscillations have all characteristic features established earlier for the secondary rhythms of endogenous contractile activity in the wall of various regions of the gastrointestinal tract and for bursts of spontaneous somatomotor excitation in the early postnatal ontogeny of rats: a multi-stage organization, inconstancy, irregularity of components. In frequency spectra of secondary oscillations of the heart rate obtained by means of fast Fourier transform of R–R intervals of the periodogram, age-related changes of the spectral frequency power are demonstrated in 4 ranges, 0.01–0.03, 0.03–0.1, 0.1–1.0, and 1.0–2.5 Hz, which correspond to the about-one-minute, decasecond, and about-one-second waves of the heart rhythm oscillations and to sinus arrhythmia. It is shown that the dominating frequencies of the secondary rhythms in each range do not have regular age-related changes, which is characteristic of all endogenous secondary rhythms.