Placental insufficiency and labor anomalies

Placental pathology, including its insufficiency, accounts for 20-28% of the causes of perinatal pathology and mortality. Chronic placental insufficiency against the background of a high degree of its immaturity and disruption of compensatory-adaptive mechanisms, primarily vascular ones, can lead to absolute placental insufficiency and numerous complications during childbirth. At the same time, the available literature does not contain information on the specific functions of the placenta and changes in its structure during complicated pregnancy and childbirth.

It has been shown that for clinicians conducting labor, the most important are the phases of compensation of placental insufficiency (compensated, subcompensated, decompensated). It has been established that each phase corresponds to certain clinical symptoms (complications of pregnancy and labor, extragenital diseases, duration of the pathological process) and various types of pharmacotherapeutic effects.

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

Universal regulators of adaptive reactions of the cell are cyclic nucleotides. The structure and hormonal function of the placenta are closely related to the metabolism of proteins, fats, carbohydrates and electrolytes. Integration of all structural and metabolic reactions is carried out in the cell - the final link of biological processes. It has been established that as pregnancy progresses, the content of cyclic nucleotides AMP and GMP increases in the placenta. With weak labor activity, the level of cAMP decreases more than 3 times, indicating the maximum decrease in adaptive mechanisms. The level of cGMP, which was 15.5 pmol/g of tissue in the control group, decreases with weak labor activity by almost 2 times (to 7.9 pmol/g of tissue).

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 action of cAMP and cGMP. The cAMP/cGMP ratio also increases as pregnancy progresses. During normal labor, this indicator is 31.7, and during weak labor, 32.9, indicating 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 were studied, the content of ribosomes, the content of glycogen in the placenta, enzymes of the pentose phosphate cycle and total lipids were investigated. The study of enzymes of the pentose phosphate cycle revealed significant differences in their content during normal labor and weakness of labor.

The activity of SDH in the placentas of the control group of women in labor is quite high due to the accumulation of blue formazan along the periphery of the villi, although there are areas with a predominance of red formazan grains. The basal membranes are clearly outlined. In cases of weak labor, a significant decrease in SDH activity was noted, with its preservation along the periphery of the villi and a predominance of red formazan compared to the control.

The enzyme activity remained at a low level (below control), being detected only at the periphery of the villi.

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

The activity of NADP in the control group was characterized by blue formazan, clearly outlining the villi due to its location on their periphery. In case of weak labor activity, some decrease in NADP activity was found, expressed in focal location of red formazan.

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

Lipid metabolism studies also revealed significant changes in total lipid levels. The decrease in total lipid levels indicates disorganization of the lipid bilayer of placental cells.

Histological and morphometric studies of placentas did not reveal changes specific to weak labor activity - the placentas of mothers in labor were visually indistinguishable from the controls. Histologically, multiple areas with circulatory disorders were determined in the form of uneven plethora of vessels of membranes and villi, focal perivascular hemorrhages, in some vessels - stasis, initial stages of thrombus formation.

In case of weak labor activity, there is a breakdown of molecular, cellular and tissue adaptive-homeostatic reactions leading to decompensated course of placental insufficiency, and this breakdown occurs within a short period of time (14-18 hours) and, in the absence of appropriate treatment, almost immediately passes into the sub- and decompensation phase. The transition to the decompensation phase in healthy women occurs more slowly than in the presence of placental insufficiency caused by obstetric and/or extragenital pathology. That is why therapy of chronic placental insufficiency undertaken before the development of weak labor activity, with the addition of the said pathology, should be intensive and continuous and take into account the negative effect of tonomotor drugs on placental homeostasis in accordance with modern principles of perinatal pharmacology.

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

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

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

Methylxanthines were used as cAMP exchange modifiers: trental at a dose of 7 mg/kg body weight and euphyllin at 4 mg/kg body weight, which are cAMP phosphodiesterase inhibitors.

In order to activate protein biosynthesis, phenobarbital was used at a dose of 40 mg/kg body weight, stimulating RNA polymerase activity and increasing the content of ribosomes in cells, and the estrogen hormone estradiol dipropionate at a dose of 50 mcg/kg body weight, which has an anabolic effect and improves uteroplacental blood circulation.

In order to protect biomembrane lipids from toxic effects, bioantioxidants and vitamins (vitamin E and Essentiale) were used: alpha-tocopherol acetate at a dose of 50 μg/kg body weight and Essentiale at a dose of 0.5 mg/kg body weight. To stimulate cAMP synthesis through the system of cellular beta-adrenoreceptors and the structural (improved microcirculation) and biochemical effects mediated by them, Alupent was used at a dose of 0.01 mg/kg body weight.

As a result of the treatment, the cAMP/cGMP ratio approached normal against the background of the use of methylxanthines.

Protein biosynthesis modifiers (phenobarbital and estradiol) have a significant normalizing effect, the latter is especially pronounced for phenobarbital. Even more promising is the use of a new drug, zixorin (Hungary), similar in its effect on microsomal oxidation to phenobarbital, but lacking a hypnotic effect. It is possible that the molecular basis for the corrective action of protein synthesis activators is the normalization of the total ribosome content and the ratio between free and membrane-bound polyribosomes.

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

The presented data substantiate the advisability of using drugs that affect not one, but several metabolic regulation pathways (Essentiale, 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 disorders in the myometrium and placenta in anomalies of labor. The failure of the humoral mechanisms of the systems that ensure labor also leads to its anomalies. At the same time, the activity of the cholinergic, sympathetic-adrenal and quinine systems decreases, a clear decrease in biologically active substances is noted - acetylcholine, norepinephrine and adrenaline, serotonin, histamine and quinines.

Prostaglandins, steroid hormones, the hypothalamic-pituitary-adrenal system of the mother and fetus, electrolytes and microelements, and oxytocin play a major role in the pathogenesis of labor anomalies.

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