TITLE:
In Vitro Characterisation of Pharmacological Effect of Prostacyclin Analogues in Comparison to Phosphodiesterase Inhibitors on Small Human Pulmonary Vessels
AUTHORS:
Azar Hussain, Robert Bennett, Zaheer Tahir, Ahmed Habib, Michael Cowen, Mubarak Chaudhry, Mahmoud Loubani, Alyn Morice
KEYWORDS:
Pulmonary Artery Rings, Human, Vasodilators, In Vitro, Pulmonary Hypertension Study
JOURNAL NAME:
World Journal of Cardiovascular Surgery,
Vol.7 No.11,
November
24,
2017
ABSTRACT: 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.