ROLE OF SEROTONIN AND ITS METABOLITE 5-HIAA IN THE DEVELOPMENT OF PULMONARY HYPERTENSION. NEW APPROACHES TO TREATMENT AND NON-INVASIVE DIAGNOSTICS?

Abstract

Objective: Development of new methods for diagnostics and new approaches to treatment of PAH from the standpoint of serotonergic regulation. The obtained data points out that a potential marker of PAH is an increase in the concentration of 5-HIAA in urine which is shown by a positive correlation with the stage of PAH. Design and method: I.The patients (n = 43, 20 days - 16 y.o.): Patients with congenital heart disease (CHD) and severe PAH; Patients with CHD with mild to moderate PAH; Healthy children (controls). II.PAH was induced in immature rats by subcutaneous injection of monocrotaline (MCT) (60 mg / kg) at the age of 4 weeks. The studies were carried out 1, 2, 4 weeks after the administration of MCT, namely: - study of 5-HIAA in urine in ELISA - invasive study of pressure in the right heart and pulmonary artery - immunohistochemical and morphological examination of the right and left ventricle, pulmonary artery and aorta. Results: A statistically significant increase in pressure in the right ventricle was found in MIPHM, which indicates the adequacy of the selected model of PAH; - Patients with PH have significantly increased plasma 5-HIAA levels compared to other groups; - There were statistically significant intergroup differences in amount of 5-HIAA in urine; - Direct positive dependence of amount of 5-HIAA in urine on the stage of PAH was revealed. Conclusions: Comparing the data of our studies, it can be concluded that 5-HIAA levels characterize the activity of pathogenetic processes in PAH. Thus, the possibility of plasma or urine 5-HIAA levels measurement in order to assess the severity of PAH and the effectiveness of its therapy is assumed. The hypothesis based on our results give us the opportunity to continue working in direction with the aim of introducing drugs of 5-HT receptor antagonists class for the PAH therapy. Simplicity, availability and non-invasiveness of the assessment method of PAH process activity makes it promising to introduce the determining of 5-HIAA levels in urine in the clinical pathology of the PAH stage and the effectiveness of its therapy.