Histological and immunohistochemical study of nerve fibers and ganglia in the periarterial adipose tissue of the pulmonary artery bifurcation in patients with and without pulmonary hypertension

Background. One of the possible methods of reducing pressure in the pulmonary artery (PA) in pulmonary hypertension (PH) is radiofrequency damage of the periarterial nerve fibers. At the same time, the impact of the autonomic nervous system has not been fully determined yet. It is also known that dopamine induces LA vasorelaxation, however, the subtypes of dopamine receptors involved in this mechanism have not yet been identified.

Objective. To assess the morphology of nerve fibers and ganglia in the periarterial adipose tissue of the PA bifurcation in patients with and without PH. Design and methods. Tissue samples of the PA bifurcation zone with surrounding fatty tissue were taken from 8 patients with PH and 9 patients without PH (autopsy material): 7 women aged 59 ± 22 years and 10 men 62 ± 15 years. An immunohistochemical reaction was performed with antibodies to S100 protein, tyrosine hydroxylase (TH), M1 muscarinic receptor, D1, D2, D5 dopamine receptors. The number of nerve fibers and ganglia per area of the preparation, their diameter and depth relative to the PA intima were estimated.

Results. There were no statistically significant differences in the structure and size of nerve fibers and ganglia in patients with and without PH. In general, the average number of nerve fibers per area of the preparation (4 cm2) was 29,1 ± 15,5; ganglia — 1,1 ± 1,3; the average fiber diameter was 130,6 ± 35,1 pm, ganglia — 532,0 ± 790,7 pm; the average fiber-intima distance was 2141,4 ± 663,3 pm, the ganglion-intima — 1799,0 ± 500,5 pm. The density of fibers around the PA bifurcation was significantly higher (p = 0,04) in patients with chronic heart failure (CHF) II NYHA functional class (FC) (20 ± 10 fibers / 4 cm2) compared to patients with CHF III-IV FC (11 ± 4 fibers / 4 cm²). The expression of M1 and TH was determined on nerve fibers and ganglia, in the endothelium and smooth muscle cells of the PA, in the epithelium of the bronchi. At the same time, unlike M1, the expression of TH was not observed in all nerve cells, and its level ranged from 1 to 4 points. No D2 receptor expression was detected, D1 expression was mild, and D5 was 4 points in all cases in the endothelium and smooth muscle cells of the LA.

Conclusions. Morphometric analysis of nerve fibers and ganglia revealed no differences between patients with and without PH. There was a significant decrease in the number of nerve fibers with the progression of heart failure. TH expression on nerve fibers and ganglia was less pronounced and was not observed in all cells as compared with the M1 receptor. Expression of dopamine receptors was detected only in the endothelium and smooth muscle cells of the PA. Further morphological study involving larger sample will allow the substantiation for the validity of the interventional innervation of the PA.

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