The <i>in Vitro</i> Characterisation of the Effect of Selexipag on Small Human Pulmonary Arteries

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.