Effect of Direct and Mediated through Maternal Organism Activation of the Catecholaminergic System on Heart Rate Parameters in Rat Fetuses.

We performed a comparative analysis of direct and mediated through the maternal organism effects of elevated catecholamine concentration on changes in the cardiac activity parameters in female rats and their fetuses on gestation days 18 and 20 under in vivo conditions. Administration of L-DOPA, a precursor of catecholaminergic transmitters, did not cause chronotropic effects in fetuses. Analysis of HR variability showed that in fetuses, irrespective of the administration route, there was an increase in nervous influences while the leading role of humoral-metabolic factors in the regulation of HR was preserved. In females receiving L-DOPA injection on day 18 of gestation, a decrease in humoral-metabolic and an increase in nerve effects were observed; in rats injected with L-DOPA on day 20 of gestation, an increase in sympathetic influences was found. Administration of L-DOPA to fetuses provoked a slight increase in the power of all components of the heart rhythm periodogram spectrum in females on day 18 of gestation and their decrease on day 20. Changes in the parameters of HR variability in females can confirm the hypothesis that in the "mother-fetus" system, the heart rhythm in the mother can be affected by both maternal and fetal influences presumably through the humoral-metabolic regulation.

Effect of Muscarinic Cholinergic Receptor Blockade on Heart Activity in Rat Fetuses.

Cardiac activity parameters were analyzed in rat fetuses with preserved placental circulation on gestation days 17-20 after administration of muscarinic receptor blocker atropine either directly to the fetuses, or to the females. The obtained results attested to the absence of chronotropic effect from the cholinergic system in rats during the fetal period. At the same time, changes in heart rate variability observed after atropine injection showed that cholinergic receptors are involved into heart rhythm regulation in rat fetuses and that their role increases from the 17th to 20th day of the embryonic period.

[QUANTITATIVE ASSESSMENT OF THE RELATIONSHIP BETWEEN SLOW-WAVE OSCILLATIONS OF HEART RHYTHM AND MOTOR ACTIVITY IN RAT FETUSES WITH FEMALE RESPIRATORY AND CARDIAC ACTIVITY].

A mathematical analysis of correlation of slow-wave processes in the system <> during the last 4 days of bearing was performed in experiments on rat fetuses with retained placental connection with the female. The parallel recording of physiological indicators of the female and fetus state revealed the existence of a relationship between oscillations of heartbeat rhythms and breathing in about-one-minute and many-minute ranges. The highest values of connection between the heart rhythms of female and fetus are characteristic for days 17 and 20 of gestation. On day 18-19 the interrelationships are slightly weaker. The specific mechanism providing this synchronization between heartbeat oscillations of mother and fetus is unclear. There are two hypothetic possibilities: an oscillation driver close in parameters for mother and fetus, and the maternal rhythm directly affecting the fetus.

[Quantitative estimation of connection of the heart rate rhythm with motor activity in rat fetuses].

In rat fetuses at E17-20 with preserved placental circulation with use of mathematical analysis there were revealed value and character of connections of slow wave oscillations of the heart rhythm with motor activity for 30 min of observation. In the software "PowerGraph 3.3.8", normalization and filtration of the studied signals were performed at three frequency diapasons: D1 - 0.02-0.2 Hz (5-50 s), D2 - 0.0083-0.02 Hz (50 s-2 min), and D3 - 0.0017-0.0083 Hz (2-10 min). The EMG curves filtrated by diapasons or piezograms were compared with periodograms in the corresponding diapasons of the heart rhythm variations. In the software "Origin 8.0", quantitative estimation of the degree of intersystemic interrelations for each frequency diapason was performed by Pearson correlation of coefficient, by the correlation connection value, and by the time shift of maximum of cross-correlation function. It has been established that in the frequency D1, regardless of age, the connection of heart rhythm oscillations with motor activity is expressed weakly. In the frequency diapason D2, the connection in most cases is located in the zone of weak and moderate correlations. In the multiminute diapason (D3), the connection is more pronounced. The number of animals that have a significant value of the correlation connection rises. The fetal MA fires in the decasecond diapason in all age groups are accompanied by short-time decelerations of the heart rhythms. In the minute diapason, there is observed a transition from positive connections at E17 and E18 to the negative ones at E19-20. Results of the study are considered in association with age-related changes of ratios of positive and negative oscillations of the heart rhythm change depending on the character of motor activity.

Dynamics of the formation of rhythmic activity of the heart in fetuses and newborn rats.

The development of heart activity and its relationship with respiratory and motor activities were studied in rat fetuses with preserved placental circulation on gestation days 15-20 (E15-20) and in newborn rats (P0). During the studied period, the heart rate in fetuses increased from 175.93±6.10 bpm (E15) to 271.82±5.93 bpm (E20). After birth, the heart rate decreased to 220.94±8.73 bpm. Heart rate variability in the decasecond and near-minute ranges was detected. At E16 stage it is presented by slow regular oscillations lasting for 20-35 sec with an amplitude of 10-45 msec. Comparison of functional activities of the cardiac and somatic motor systems showed that at E16, fluctuations in heart rate are independent of the bouts of motor excitation. During growing, the degree of synchronization of heart rate variability with physical activity increased. E17-18 stage is characterized by short-term episodes of heart rate deceleration associated with motor activity; their duration and amplitude did not depend much on the force of movement. At E19-20, decelerations typical of early gestation terms were replaced by acceleration-type reactions typical for mature organism, which is related to maturation of coordination function of the nervous system. In the heart rhythm, respiratory arrhythmia appears during episodes of rhythmic breathing. Newborn rats demonstrated acceleration episodes; their parameters depend on the force of motor bouts; respiratory arrhythmia was not observed.

[Effect of change in activity level of catecholaminergic systems on motor, respiratory, and cardiac activities in rat embryos].

Parameters of motor, respiratory and cardiac activities were studied in rat embryos (E17-20) after changes in activity level of catecholaminergic systems. To produce conditions for excessive level of catecholamines, the animal were administered individually with preparation of L-DOPA at doses of 25, 50 and 100 mg/kg. Also studied was action of L-DOPA after blockade of D1-(antagonist - SCH-23390, 0.1 mg/kg), D2-(antagonist - sulpiride, 50 mg/kg) dopaminic, and beta2-(antagonist - propranolol, 1 mg/kg) adrenergic receptors. It was found out in E17-18 that the DOPA administration regardless of dose, while in E19-20 dose-dependently produces continuous generalized activity. Between E18 and E19, ontogenetically new is the appearance in 92 % of embryos of stereotypical head movements (circular movements, lateral and dorso-ventral flexions) following in the nearsecond rhythm. Injection of DOPA to rat embryos increased 2-6 times the number of respiratory movements by the gasping type in E17-20 and decreased the amount of episodes of continuous rhythmical respiration in E19-20. No significant heart rate changes were observed after introduction of DOPA to E17-20. There was noted a tendency for a weak acceleration of the heart rate. The changes in activities of the motor and respiratory systems due to a rise of catecholamine level are not connected with activation of the dopamine system, as they are not reduced by blockade of dopamine receptors.

[Study of cardiac, respiratory, and motor activity in rat fetuses].

Development of the cardiac, respiratory, and motor activity was studied in rat fetuses with preserved placenta circulation was studied at the 16th, 18th, and 20th gestation days. The presence of three main movement types has been found: complexes of generalization activity, local movements, and jerks. In development of respiratory function, there is observed a gradual transition from individual inspirations to series of respiratory movements and then to formation of periodic respiration episodes. At the studied period, the heart rate has been found to increase. The existence of the slow-wave modulations it the heart rate with a period of 20-40 s has been revealed. Analysis of interrelations between the respiratory and motor systems has shown that in the 16-day fetuses, each respiratory movement is accompanied by extensor jerk. By the 20th days of embryonic development (E20), uncoupling of the respiratory and motor activities occurs. Comparison of the activity observed in the cardiac and somatomotor systems has shown that at E16, the cardiac rhythm fluctuations do not depend on the motor excitation jerks. In the 18-day fetuses, brief slowing down (decelerations) of the cardiac rhythm appeared during the motor activity jerks, whereas at E20, on the contrary, an increase of frequency (accelerations) of the cardiac rhythm occurred.

[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.

[Peculiarities of regulation of high-frequency oscillations of cardiac rhythm in rat ontogenesis].

Dynamics of high-frequency components of heart periodogram whose main part is respiratory arrhythmia (RA) as well as consequences of vagotomy, block of M-cholinoreceptors by atropine and of beta-adrenoreceptors by propranolol was studied in Wistar white rats in a large age diapason from 2-4 days to adults. It was established that results of the actions in immature rats did not essentially differ from those observed in adult rats and described in animals of other species and in human. In rats of young age, predominant in genesis of RA is peripheral mechanism. Vagotomy produces an elevation of the RA amplitude due to a sharp increase of the inspiration time as well as to deafferentation. Sympathetic nervous system produces restricting action on RA. This role is preserved in animals of all age groups. Participation of parasympathetic innervation in the RA genesis is revealed from the third week and continues increasing to the mature age. However, in adult rats, the peripheral mechanism of the RA formation is preserved, as disturbance of parasympathetic innervation leads not to the disappearance of RA, but only to a decrease of its amplitude.

[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.

[The possible pathways of age-related inhibition of the spinal generators of motor excitation in rat pups]. / O vozmozhnykh putiakh vozrastnogo tormozheniia spinal'nykh generatorov motornogo vozbuzhdeniia u krysiat.

In experiments on rat puppies, it has been demonstrated that cutting the dorsal part of the spinal cord at the 10th day of postnatal life results at the 17-18th day in a relative hyperactivity, which is revealed in significantly higher volume of the spontaneous motor activity, duration and number of discharges, as well as in significant facilitation of reactions of late discharge type. Therefore, in rat puppies, the pathways of age inhibition of the activity of spinal pacemakers of motor excitation are located in dorsal and dorsolateral parts of the spinal cord.