Endothelial dysfunction and its role in the prevention, treatment and complications of critical conditions in obstetrics
Authors: Jong-Din Kim 
Published: July 2021

Background. Preeclampsia (PE) remains the leading cause of maternal and perinatal morbidity and mortality. As of today, there is no treatment for PE, and the childbirth is the only way to completely eliminate this condition. However, early childbirth is associated with a high risk of fetal morbidity and mortality.

Objective. To describe the role of endothelial dysfunction (ED) in the development of PE and the possibility of its correction; to evaluate the effectiveness of Tivortin (“Yuria-Pharm”) in the correction of uterine-fetal-placental dysfunction.

Materials and methods. Analysis of literature sources on this topic; own PLACENTA study. The study involved 535 women with mild PE at 26-29 weeks of gestation. Group I received standard therapy, group II – standard therapy in combination with Tivortin (4.2 g per day for 7-10 days).

Results and discussion. Until the fetus reaches viability, PE treatment is aimed at correcting hypertension, however, antihypertensive therapy does not have a beneficial effect on the condition of the kidneys and placental blood flow. Decreased blood flow in placenta leads to the syndrome of limited fetal development (SLFD) and multisystem ED. The development of PE is inextricably linked with the systemic damage to maternal endothelial cells and a further decrease in endothelium-dependent vasodilators, which promotes vasospasm and activates the coagulation cascade. PE is accompanied by the imbalance in the systems of prostacyclin and nitric oxide (NO), as well as thromboxane and endothelin. Superficial placentation with insufficient remodeling of the spiral arteries and impaired response to changes in blood flow is one of the main causes of PE. ED is the most studied pathogenetic mechanism of PE. NO has a potent vasodilating effect and is involved in inhibiting thromboxane formation, platelet aggregation and stimulating prostacyclin formation. NO-synthase of endothelial cells, the substrate of which is L-arginine, is the main enzyme of NO production. Disorders of vasodilation in pregnant women with PE can be eliminated by prescribing L-arginine. Literature data show that L-arginine is successfully used in the need to continue pregnancy, as well as to eliminate hypertension and correct SLFD. Canadian guidelines for the treatment of hypertensive complications of pregnancy state that L-arginine is able to improve uteroplacental blood flow. According to a study by J. Chen (2016), the inclusion of L-arginine contributes to both maternal and perinatal outcomes of pregnancy. The effect of L-arginine on fetal growth is mediated by promoting the production of creatine, skeletal muscle protein and growth hormone. L-arginine also promotes the synthesis of polyamines, which can stimulate the growth and development of placenta. Own studies have shown that the use of L-arginine (Tivortin, “Yuria-Pharm”) in the combined PE therapy had improved the growth rate of the fetus and its functional condition, which allowed to prolong pregnancy to the optimal term of childbirth, as well as improve the consequences of childbirth and adaptation of newborns in the early neonatal period. PE is not the only field of application of Tivortin: its intravenous administration in community-acquired pneumonia and pyelonephritis of pregnant women helps to quickly eliminate the pathological process. The results of the PLACENTA study found that Tivortin helped to improve uterine-fetal-placental blood flow and reduce the centralization of blood circulation. In the Tivortin group there was a smaller number of cesarean sections, a tendency to lower blood loss (by 19.5 %), a higher average score of newborns on the Apgar scale. Comparison of clinical and morphological changes showed that the administration of Tivortin in the late second and early third trimester of pregnancy reduces the likelihood of premature placental maturation by 2.1 %, halves the likelihood of placental necrosis, 10 times reduces the signs of hypoxia.

Conclusions. 1. ED, caused by a decrease in NO, is the main link in the PE pathogenesis. 2. In the human body NO is produced from L-arginine. 3. The use of L-arginine (Tivortin) improves uterine-fetal-placental blood flow, growth rate and functional status of the fetus, reduces fetal distress and allows to prolong pregnancy to the optimal term of childbirth.