Introduction: Asthma is a chronic inflammatory disease affecting the small airways. A relevant animal model allowing investigation of intralobular bronchi (ILB) would be of great interest for asthma research. The aim of this study was, therefore, to create a small airway ex-vivo model of guinea pig (GP) ILB and investigate functional responses.
Methods: GP (N=16) were sacrificed with an overdose of pentobarbital. Directly after death, the lungs were filled with Krebs-Henseleit buffer containing 1?M salbutamol, followed by the removal of the heart-lung package. Subsequently, the small airways located within the lung parenchyma were carefully dissected free into small airway segments, which were incubated in DMEM-F12 for 48h before functional experiments using myographs recording isometric tension. The following pharmacological agonists were investigated:
| Contractile study | Relaxant study (0.3µM CCh pre-contraction) |
| Histamine Carbachol (CCh) Thromboxane (TP) receptor agonist (U46619) PGE2 EP1 and EP3 receptor agonist (sulprostone) |
PGE2 |
Results: Histamine, CCh and U46619 induced concentration-dependent contractions (Emax 133±12%, 119±9%, 102±10%, respectively, compared to 60 mM KCl). Neither PGE2 nor sulprostone induced a contraction. In CCh pre-contracted segments, both PGE2 and ONO-AE1-259 caused concentration-dependent relaxations (Emin 44±7%, 47±14%, respectively).
Conclusion: This study presents a novel translational ex-vivo small airway model enabling functional characterizations, thus adding a valuable tool for asthma research.