Placental insufficiency and anomalies of the ancestral forces

The pathology of the placenta, including its insufficiency in the structure of the causes of perinatal pathology and mortality is 20-28%. Chronic insufficiency of the placenta against the background of a high degree of its immaturity and the violation of compensatory-adaptive mechanisms, primarily vascular, can lead to absolute placental insufficiency and numerous complications in childbirth. At the same time, in the available literature there is no information on the specific functions of the placenta and changes in its structure in the complicated course of pregnancy and in childbirth.

It is shown that for clinicians leading the birth, the most important are the phases of compensation of placental insufficiency (compensated, subcompensated, decompensated). It is established that each phase corresponds to a certain clinical symptomatology (complications of pregnancy and childbirth, extragenital diseases, duration of the pathological process) and various types of pharmacotherapeutic effects.

The compensation phases were developed on the basis of the study of the molecular, cellular and tissue adaptation-homeostatic reactions of the placenta.

Universal regulators of cell adaptations are cyclic nucleotides. The structure and hormonal function of the placenta is closely related to the metabolism of proteins, fats, carbohydrates and electrolytes. Integration of all structural and metabolic reactions is carried out in a cell - the final link of biological processes. It was found that as the pregnancy progresses in the placenta, the content of cyclic nucleotides AMP and HMF increases. With the weakness of labor, the level of cAMP decreases more than 3-fold, indicating a maximum decrease in adaptive mechanisms. The cGMP level, which in the control group is 15.5 pmol / g tissue, is reduced almost twice (to 7.9 pmol / g tissue) when the birth activity is weak.

Of particular interest are not only the dynamics of changes in the content of cyclic nucleotides, but also the ratio between them, since most cellular reactions are mediated by the combined effect of cAMP and cGMP. The ratio of cAMP to cGMP as pregnancy progresses is also increasing. At normal delivery, this indicator is 31.7, with weakness of labor activity - 32.9, which indicates the preservation of the hierarchical regulation of the adaptive homeostatic reaction.

The molecular mechanisms of protein biosynthesis in the placenta in the dynamics of pregnancy have been studied, the content of ribosomes, the content of glycogen in the placenta, the enzymes of the pentose phosphate cycle and total lipids have been studied. Investigation of the enzymes of the pentose-phosphate cycle revealed significant differences in their content during normal delivery and weakness of labor.

The activity of SDH in the placentas of the control group of parturient women is quite high due to the accumulation of blue formazan at the periphery of the villi, although there are areas with a predominance of red formazan grains. The basal membranes are clearly delineated. With the weakness of labor activity, there was a significant decrease in SDG activity with its preservation along the periphery of the villi and the predominance of red formazan compared with the control.

The enzyme activity was kept at a low level (below the control), revealing itself only around the periphery of the villi.

The activity of NAD in the control group was quite high - a well-pronounced blue formazan was determined with a special activity at the periphery of villi in the zone of syncytial points. With the weakness of labor activity, a decrease in the activity of NAD with a predominance of red formazan in zones of usual localization was noted.

The activity of NADP in the control group was characterized by a blue formazan, clearly defining the villi, due to its location along their periphery. With the weakness of labor activity, a certain decrease in the activity of NADP was found, expressed in the focal location of the red formazan.

The activity of G-6-PD in the placentas of the control group of parturient women was quite high, the fine-dispersed blue formazan was evenly distributed around the periphery of the villi. A significant decrease in the activity of G-6-PD was noted in the case of weakness in labor activity, it was retained mainly due to red formazan located in the form of separate clusters alternating with areas of almost complete absence.

The study of lipid metabolism also revealed significant changes in the content of total lipids. A decrease in the content of total lipids indicates disorganization of the lipid bilayer of placental cells.

Histological and morphometric studies of the placenta revealed no changes specific to the weakness of the labor activity, the placentas of the puerperas did not visually differ from the control ones. Histologically, multiple sites were identified with circulatory disorders in the form of uneven embolism of the vessels of the membranes and villi, focal perivascular hemorrhages, in the vessels part - stasis, the initial stages of thrombo-formation.

With the weakness of labor activity, the molecular, cellular and tissue adaptation-homeostatic reactions are broken, leading to a decompensated course of placental insufficiency, and this disruption occurs within a short time (14-18 hours) and, in the absence of appropriate treatment, almost immediately goes into the sub- and decompensation. The transition to the phase of decompensation in healthy women is slower than in the presence of placental insufficiency due to obstetric and / or extragenital pathology. That is why the therapy of chronic placental insufficiency, undertaken before the development of the weakness of labor, when joining this pathology, should be intense and continuous and take into account the negative impact of tonomotor drugs on placental homeostasis in accordance with modern principles of perinatal pharmacology.

There is almost no information on changes in biochemical parameters of placental metabolism under the influence of various drugs used in obstetric practice. The main objectives of the use of drug therapy were:

• protection of the biological membrane;
• activation or (more often) maintenance of a high level of cAMP and cGMP;
• increase of protein-synthesizing activity of cells;
• restoration of equilibrium of metabolic pathways of bioenergetics (activation of glycolysis enzymes and stimulation of microsomal oxidation).

For the purposeful correction of metabolic disorders in cells caused by damage to membranes and a protein synthesizing apparatus, various groups of drugs have been studied.

As modifiers of cAMP exchange, methylxanthines were used: trentalum at a dose of 7 mg / kg of mass and euphyllin - 4 mg / kg of mass, which are inhibitors of cAMP phosphodiesterase.

In order to activate the protein biosynthesis, phenobarbital 40 mg / kg of mass stimulating RNA polymerase activity and increasing ribosomal content in cells was used, and estrogenic hormone-estradiol-dipropionate at a dose of 50 μg / kg of body weight with anabolizing effect and improving uterine- placental circulation.

To protect lipids of biomembranes from toxic effects, bioantioxidants and vitamins (vitamin E and essential oil) were used: alpha-tocopherol acetate in a dose of 50 mcg / kg of mass and essential at a dose of 0.5 mg / kg of body weight. To stimulate the synthesis of cAMP through a system of cellular beta-adrenergic receptors and the structural (improving microcirculation) and biochemical effects mediated by them , alupent was used at a dose of 0.01 mg / kg of mass.

As a result of the treatment, the cAMP / cGMP ratio against the background of the use of methylxanthines was approaching the norm.

Modifiers of protein biosynthesis (phenobarbital and estradiol) have a significant normalizing effect, the latter is especially pronounced in phenobarbital. Even more promising is the use of a new zixorin drug (Hungary), similar in its effect on microsomal oxidation with phenobarbital, but devoid of hypnotic effect. It is not excluded that the molecular basis for the corrective action of activators of protein synthesis is the normalization of the total content of ribosomes and the relationship between free and membrane-bound polyribosomes.

The effect of alpha-tocopherol on placental metabolism is similar to estradiol.

The presented data justify the expediency of using drugs that affect not one but several ways of metabolic regulation (essential, alupent, phenobarbital, euphyllin, trental, alpha-tocopherol) for the treatment of placental insufficiency.

Thus, studies conducted by many modern authors have shown the importance of metabolic disturbances in myometrium and placenta in anomalies of labor. The inconsistency of the humoral mechanisms of the systems providing for the generic activity also leads to its anomalies. At the same time, the activity of cholinergic, sympathic-adrenal and quinine systems decreases, a clear decrease in biologically active substances - acetylcholine, noradrenaline and adrenaline, serotonin, histamine and quinine.

Great importance in the pathogenesis of abnormalities of labor is assigned to prostaglandins, steroid hormones, hypothalamic-pituitary-adrenal system of mother and fetus, electrolytes and trace elements, oxytocin.

[1], [2], [3], [4], [5], [6], [7], [8], [9], [10], [11]