TITLE:
The in Vitro Characterisation of the Effect of Selexipag on Small Human Pulmonary Arteries
AUTHORS:
Salman Arif, Mohamed Abdi, Bilal Qaddoura, Ghazi Elshafi, Syed Qadri, Mubarak Chaudhry, Mahmoud Loubani, Azar Hussain
KEYWORDS:
Pulmonary Arterial Hypertension, Selexipag, Human Pulmonary Artery, Prostacyclin, Vasodilation
JOURNAL NAME:
World Journal of Cardiovascular Surgery,
Vol.12 No.12,
December
31,
2022
ABSTRACT: Objective: There is a lack of data on the direct effects of
Selexipag, a novel prostacyclin Inositol phosphate-3 receptor (IP3) agonist
with a long half-life, on human pulmonary arteries. This study aims to
establish the efficacy and potency of Selexipag on human pulmonary arteries. Methods: Patient consent was obtained prior to lung
resection for primary lung cancer. The pulmonary artery rings (n = 23 from 6
patients) were cut to 2 - 4 mm length and 2 - 4 mm internal diameter. They
were mounted on a wire myograph under physiological
conditions and were pre-constricted to prostaglandin F2α. Concentration response curves were constructed to
Selexipag by cumulative addition to the myograph chambers. The viability of the
rings was confirmed with Acetylcholine and potassium chloride. Results: The Selexipag caused dose dependent vasodilation to
human pulmonary arteries. The range of doses used was from 1 pM to 30 uM, n = 4 were excluded
due to non-reactivity and n = 19 were included. Initial significant
vasodilation of PAs was noted at 3 uM. Maximal response was achieved at 10 uM of Selexipag (EC50 =
1.21 uM). Conclusion: The study demonstrated the vasodilatory effect of
Selexipag on PAs. Selexipag may be clinically effective in the treatment of
pulmonary arterial hypertension. However, additional data are needed to validate the
results of this study and determine its clinical significance.