Physiological responses of the airway wall and lung in hyperresponsive pigs

Abstract

Airway hyperresponsiveness (AHR) might be driven by mechanisms inherent to the airway wall, and/or by factors arising from outside the airways. A porcine model of allergen-induced AHR was utilized to investigate physiological responses in intact airways in vitro and their contribution to responsiveness in vivo. Responsiveness to acetylcholine (ACh) was measured in eight ovalbumin (OA)-sensitized/challenged pigs (tests) and eight saline-challenged controls. In vivo responsiveness to ACh was determined from pulmonary resistance (RL). In vitro responsiveness to ACh was determined from airway pressure in isovolumic bronchial segments, after exposure via the adventitial or the luminal surface. Test pigs had lung (255±26% increase in RL, p<0.0001) and skin responses to OA, and AHR to ACh (p<0.0001). In vitro, test bronchi were less sensitive than controls to ACh applied to the airway adventitia (negative log of the ACh concentration producing half the maximum response (pD2)=4.18 and 4.58 respectively, p<0.01), but not the lumen. Test bronchi had an increased amount of smooth muscle normalized for airway size versus controls (p<0.05). Maximum responses to lumenal ACh in vitro showed a weak positive correlation with maximum changes to ACh in vivo (r=0.599, p=0.05). This study concludes that the effect of antigen challenge on bronchial responsiveness varies with the route of exposure to acetylcholine. In vitro responses to lumenal acetylcholine are increased despite a possible reduction in responsiveness of airway smooth muscle. Responsiveness of the bronchial wall only partially explains responsiveness of the lungs in vivo.