iIn Vitro/iCharacterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels

摘要

Background and Aim of Study: The phosphodiesterase inhibitors (Sildenafil and Milrinone), Nitric Oxide donor Sodium Nitroprusside (SNP) and prostacyclin analogs are commonly used pulmonary vasodilators to treat pulmonary hypertension. In the past few years, we have used human pulmonary artery rings in vitro to evaluate pulmonary vascular resistance. The main objective of the current study is to document the pharmacological impact of clinically used prostacyclin analogs on the human pulmonary system in parallel with phosphodiesterase inhibitors and SNP. Methods: The study used human pulmonary artery rings of internal diameter of 2 - 4 mm and length of 2 mm. These were extracted from patients with lung resections. These rings were then mounted on a multiwire myograph, and changes in isometric tension were noted. Then, concentration response curves were constructed to Sildenafil (Sd), Milrinone (Mil), Sodium Nitroprusside (SNP), Epoprostenol (Ep), Iloprost (Ip) and Treprostinil (Tp). Results: 52 pulmonary artery rings were used in these experiments. Sildenafil, Milrinone, SNP, Epoprostenol, Iloprost and Treprostinil caused a concentration-dependent vasodilation in small human pulmonary arteries (pEC50: 5.97 ± 0.22, 5.99 ± 0.12, 7.64 ± 0.08, 7.53 ± 0.14, 8.84 ± 0.15 and 9.48 ± 0.13 respectively, n = 8 to 12). The efficacy for the same was in the order: Tp = Ip > Ep > Mil > SNP > Sd. The potency varied in the order: Tp > Ip > SNP > Ep > Mil > Sd. Conclusion: This research showed the efficacy as well as the potency of SNP and phosphodiesterase inhibitors and prostacyclin analogs on the human pulmonary vasculature. Treprostinil and Iloprost exhibited maximum relaxation. However, Sildenafil and SNP showed lesser impact. These effects need to be considered for clinical studies for enhanced patient outcomes.