Possibility of evaluation of oxygen transport function in PAH patients on effective selexipag-based therapy

In the complex pathogenesis of idiopathic pulmonary arterial hypertension (IPAH), which includes changes in biochemical and biophysical processes in various cell types as the cause of structural and functional impairment, inflammation and thrombosis of the pulmonary vessels, hypoxia also plays an important role due to conformational changes in hemoglobin molecules with changes in their structure and oxygen transport function impairment.Aim: Using the method of Raman (Raman scattering) spectroscopy, to study changes in the conformation and ability of hemoglobin (Hb) to bind oxygen in blood erythrocytes from the cubital vein in IPAH patients and healthy people. Materials and methods: The study included 39 patients with newly diagnosed IPAH with functional class I - 2 patients, II - 13 patients, III - 22 patients, IV - 2 patients. 15 patients were treatment naive. In 24 patients a “washout” period of trial therapy was conducted for 5-7 days. The control group included 10 healthy volunteers.Results: It was established that the Raman spectra of Hb of whole blood erythrocytes and isolated red blood cells (RBC) of IPAH patients have significant differences from the control group. The IPAH group was characterized by an increase in the probability of finding heme in a «dome-shaped form», which is typical for the deoxygenated form of Hb, changes in the conformation of globin and the porphyrin macrocycle were revealed. A significant role in the change in the oxygen-transport function of Hb in IPAH was played by a change in the conformation of membrane-bound hemoglobin, which was characterized by an increase in the contribution of symmetrical vibrations of pyrrole rings in hemoporphyrin relative to the control, which required further study. Probably, the reason for the decrease in the ability of the oxygen transport function of membrane-bound hemoglobin was the decrease in the efficiency of electrostatic interaction with the protein of band 3. In clinical case positive changes in spectroscopy parameters were shown in IPAH patient with the effective use of selexipag.Conclusions: For the first time, the possibility of using a non-invasive method of Raman spectroscopy to study changes in the oxygen transport function of erythrocytes in IPAH patients has been proven, which can serve as an additional method in the diagnostic algorithm of this disease.