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.

[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 formation of activity-rest cycles in early ontogeny]. / Formirovanie tsiklov aktivnost'--pokoi v rannem ontogeneze.

The cyclic variations of the motor activity consist of many rhythmic components which appear nonsimultaneously in the ontogenesis. The earliest component is the autogenic periodic motility with the duration about one minute which can be observed in rats during first two-three weeks after the birth. From the second week a new type of cyclic activity appears. It can be qualified as a sleep-wakefulness cycle with the duration about several minutes. It is suggested that this cycle is a true novel rhythm which is able to modulate the earliest more frequent periodicity.

[The effect of 6-hydroxydopamine on the autogenic motor activity of newborn rat pups]. / Vliianie 6-oksidofamina na autogennuiu motornuiu aktivnost' novorozhdennykh krysiat.

At the 1st, 2nd and 3rd days after birth, subcutaneous injections of 6-oxydopamine in physiological solution containing 0.1% of ascorbic acid have been made to rat puppies in a dose 100 mg/kg per one injection. Within first three weeks, electromyographic studies were made on outbursts of autogenic periodic motor activity which is typical of animals at this age. It was shown that at the 3rd day of postnatal life, after 6-oxydopamine administration, total duration of motor excitation is significantly lower, whereas mean duration of the outbursts of continuous activity is lower even at the 7th day. Beginning from the 10th day, these parameters undergo opposite changes at the background of the increase in the number of outbursts and the decrease of intervals between the latter. The data obtained are discussed in relation to the role of catecholaminergic systems in regulation and realization of age dynamics of autogenic motor activity.

[The role of the dopamine and noradrenaline systems in regulating autogenic motor activity in rat pups]. / O roli dofaminovoi i noradrenalinovoi sistem v reguliatsii autogennoi motornoi aktivnosti krysiat.

In experiments on 3-day rat puppies, studies have been made of the effect of a stimulator of noradrenaline receptors--clonidine, and a stimulator of dopamine receptors--apomorphine on autogenic motor activity. It was shown that clonidine injections result in a significant increase of this activity, whereas apomorphine slightly decreases the latter. The data obtained in the present work together with those described earlier for l-DOPA effects, suggest that double regulation of autogenic activity is realized at early stages of ontogenesis. This regulation includes excitatory noradrenergic mechanisms and inhibitory influences which are mediated presumably by dopaminergic systems of the brain.

[The action of L-DOPA on the structure of spontaneous motor activity in rat pups]. / Deistvie L-DOFA na strukturu spontannoi motornoi aktivnosti krysiat.

In experiments on 2-3-, 7-8-, 10- and 16-day old rat pups, basic age differences have been observed in the effect of a precursor of catecholamine mediator, i.e. L-DOPA on the activity on the spinal and brain mechanisms of autogenic periodic motor excitation. Strong stimulation of the spinal motor rhythm was observed during the first week. At this period, supraspinal rhythm becomes even less evident. On further development, the effect is an opposite one. In 10- and 16-day rat pups, at the background of total inhibition of the spontaneous activity, administration of L-DOPA significantly increases the activity of supraspinal generator of the motor rhythm. The data obtained reveal ontogenetic changes in regulatory mechanisms of autogenic motor activity.