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.

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