Diagnosis of labor anomalies

The central problem in modern obstetrics is the regulation of labor activity, since the clarification of the nature of the mechanisms stimulating the contractile activity of the uterus is a necessary prerequisite for reducing the number of pathological births, surgical interventions, hypo- and atonic bleeding and reducing perinatal mortality. At present, groups of pregnant women at high risk for the development of labor anomalies have been identified.

The introduction of new pharmacological drugs and non-drug methods of treatment into medical practice has significantly expanded the capabilities of practicing physicians in the treatment of anomalies of labor. However, this has not solved the problem of regulating smooth muscle tone, since it is largely due to the prevalence of empirical methods in the process of searching for new drugs, especially in the search for myotropic drugs, and the current lack of sufficiently deep knowledge of the mechanisms that form the tone of smooth muscles during complicated pregnancy and labor and contractile activity of the uterus during labor.

In the course of many years of research into the nature of muscle contraction, significant progress has been made in solving the central problems of biological mobility:

• identification of the ultrastructure of the contractile apparatus;
• study of the physicochemical properties and mechanisms of interaction of the main contractile proteins - actin and myosin;
• searching for ways to convert the chemical energy of adenosine triphosphate (ATP) into mechanical energy;
• in a comparative analysis of the morphofunctional properties of contractile systems of various muscle cells.

The issues of regulation of muscle activity have only begun to be addressed in the last decade, and these studies are focused primarily on identifying the trigger mechanisms of the contractile act itself.

It is now generally accepted that the mechanical work performed by various contractile systems of a living cell, including the mechanical work of a contracting muscle, is performed by the energy accumulated in ATP and is associated with the functioning of actomyosin adenosine triphosphatase (ATPase). The connection between the process of hydrolysis and contraction is undeniable. In addition, understanding the molecular mechanism of muscle contraction, which also requires precise knowledge of the nature of muscle contraction and the structural interaction between actin and myosin, will further deepen our knowledge of the molecular processes associated with the work of actomyosin ATPase.

The biochemical mechanisms that regulate the energy and contractile apparatus of the muscle cell are analyzed, and the relationship of these biochemical mechanisms of ATPase control with the phenomenon of muscle fatigue is discussed. The indicators of fatigue in a contracting muscle are a decrease in the force of contraction and the rate of its increase, as well as a decrease in the rate of relaxation. Thus, the magnitude of the force developed by the muscle during a single contraction or in an isometric mode, as well as the maximum speed of muscle shortening, are proportional to the activity of actomyosin ATPase, and the rate of relaxation correlates with the activity of reticulum ATPase.

In recent years, more and more researchers have been paying attention to the study of the features of regulation of smooth muscle contraction. This has led to the emergence of various, often contradictory points of view, concepts, and hypotheses. Smooth muscles, like any other, contract in the rhythm of the interaction of proteins - myosin and actin. In smooth muscles, a dual system of Ca ²⁺ regulation of actin-myosin interaction, and therefore contraction, has been demonstrated. The presence of several pathways for regulating actin-myosin interaction, apparently, has great physiological meaning, since the reliability of regulation increases with the activity of two or more control systems. This seems to be extremely important in maintaining such homeostatic mechanisms as control of arterial pressure, labor, and others associated with the work of smooth muscles.

A number of regular changes in physiological and biochemical parameters characterizing the relaxation of smooth muscles under the influence of drugs, especially antispasmodics, have been established: an increase in membrane potential observed simultaneously with the suppression of spontaneous or evoked peak activity, a decrease in oxygen consumption by smooth muscles and the content of ATP in them, an increase in the concentration of adenosine diphosphoric acid (ADP), adenosine monophosphoric acid (AMP) and cyclic 3,5-AMP.

To understand the nature of the intracellular events involved in the process of myometrial contraction and its regulation, the following model is proposed, which includes four interrelated processes:

• interaction of a signal (eg, oxytocin, PGEg) with membrane receptors of the myometrial cell or with electrical depolarization of the cell membrane;
• calcium-stimulated translocation of phosphatidylinositol within the membrane and release of inositol triphosphate (a potent intracellular activator) and arachidonic acid;
• synthesis of prostaglandins (PGEg and PGF2 ₎ in the myometrium, which leads to an increase in the intracellular concentration of calcium and the formation of junction points in the intercellular spaces;
• calcium-dependent phosphorylation of myosin light chain and muscle contraction.

Myometrial relaxation is achieved through cyclic AMP and protein kinase C-dependent processes. Endogenous arachidonic acid released during muscle contraction can be metabolized to PG12 _, which stimulates cAMP production by activated receptors. Cyclic AMP activates A-kinase, which catalyzes the phosphorylation of myosin light chain kinase and phospholipase C (a phosphodiesterase involved in phosphatidylinositol metabolism), inhibiting their activity. Cyclic AMP also stimulates calcium deposition in the sarcoplasmic reticulum and calcium extrusion from the cell.

Prostaglandins (both endogenous and exogenous) have a number of stimulating effects on the myometrium.

First, they may act on secretory membrane receptors, stimulating the flow of phosphatidylinositol within the membrane and subsequent events leading to calcium mobilization and uterine contraction.

Second, excitatory prostaglandins (PGE2 _and PGF2 ₎, synthesized in the myometrium after the release of arachidonic acid, can mobilize more calcium from the sarcoplasmic reticulum and increase transmembrane calcium movement by acting as ionophores.

Third, prostaglandins increase electrical coupling of cell circuits by inducing the formation of junction points in intercellular spaces.

Fourth, prostaglandins have high diffusion capacity and can diffuse through cell membranes, thereby enhancing cell adhesion biochemically.

It is known that the myometrium is sensitive to the action of exogenous prostaglandins during pregnancy. The introduction of prostaglandins or their precursor - arachidonic acid - allows to bypass local suppression of prostaglandin biosynthesis by the inhibitory effect of phospholipase. Therefore, exogenous prostaglandins can find access and stimulate a cascade of intracellular events leading to synchronization and strengthening of myometrial contractions.

Such prostaglandin effects will result in an increase in the initial stimulatory signal (whether it be fetal or maternal oxytocin, or prostaglandins from the amnion or from the sloughing uterine membrane) and an increase in the intensity of contractions due to an increase in both the number of active cells and the power of contraction generated by a single cell.

The processes that contribute to the development of labour-related uterine contractions are interrelated, and each process may have additional metabolic bypasses at any level, with the result that the desired actions of certain drugs (eg, tocolytics) may not be achieved.

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