Pharmacological studies of bronchial constriction inhibited by parasympatholytics and cilomilast using equine precision-cut lung slices.

This research article demonstrates the effectiveness of various drugs (atropine, ipratropium, tiotropium, and cilomilast) in reducing bronchial constriction caused by methacholine in horse lung tissue, with implications for treatments of bronchial diseases.

Research Methodology and Experimental Design

• The researchers used precision cut lung slices (PCLS) from 20 horses, collected after euthanasia and comprehensive lung examination.
• The tissue samples were gathered from three different lobes – cranial, caudal, and accessory – for a detailed histological examination.
• PCLS with an average thickness of 250 +/- 20 micrometers exhibited viability, confirmed observing the movement of cilia and bronchial contraction when exposed to increasing concentrations of methacholine (MCh), a substance that induces bronchial constriction.
• The bronchial tubes were made to reopen by washing the lung slices with pure RPMI (Roswell Park Memorial Institute) medium.

Drug Incubation and Effect Assessment

• The lung slices were incubated for 20 minutes in an RPMI solution containing either atropine, ipratropium, tiotropium (each at 10(-7) mol/l concentration), or cilomilast (at 10(-5) mol/l concentration).
• Each group of lung slices was then subjected to methacholine treatment again.
• The unaffected viability of lung slices after reopening was confirmed by reapplying MCh.
• The half-maximal effective concentration (EC50) values of MCh – which represent the concentration of MCh at which 50% maximum contraction occurs – were calculated for each contraction from bronchial slices.

Research Results and Conclusion

• The research observed a significant increase in EC50 values following the application of atropine, ipratropium, and tiotropium, suggesting a reduced contractile response, hence, bronchodilatory effects of these compounds.
• There were no observable differences with cilomilast or within control slices.
• The statistical analysis pointed out a significant variation between individual horses but only small differences within an individual.
• There was no correlation observed between the clinical examination, histological findings, and the responsiveness of PCLS’s to the methacholine.
• The results of this research supported those of Vietmeier’s 2007 study on the responsiveness of equine PCLS to MCh, but it also provided insight into the bronchodilatory effects of several new drugs using a technique that facilitates substance assessment in the same horse.