Airway and tissue responses to antigen challenge in sensitized brown Norway rats

It has recently been shown in several species that lung tissue resistance increases after administration of exogenous bronchoconstrictors. This finding suggests the possibility that lung parenchymal tissues could be involved in the pathophysiology of pulmonary allergic responses. To test this hypothesis, we sensitized Brown Norway rats with ovalbumin (OA) and performed experiments in anesthetized, open-chested, mechanically ventilated (respiratory frequency [f] = 1 Hz, tidal volume [VT] = 9 ml/kg, positive end-expiratory pressure [PEEP] = 3 cm H2O) animals. We affixed alveolar capsules to the lungs to measure alveolar pressure and calculated the resistance of lung (RL), tissue (Rti), and airway (Raw) under control conditions and after aerosol administration of saline (S) (n = 10) or OA (n = 14). To assess lung morphometry during the late response, the lungs of six S and six OA animals were frozen with liquid nitrogen (PEEP = 3 cm H2O) and processed via freeze substitution. Airway constriction was assessed by measuring the ratio of the airway lumen (A) to the ideally relaxed airway (Ar). Tissue distortion was assessed by measuring the mean linear intercept between alveolar walls (Lm), an atelectasis index (ATI) derived by calculating the ratio of tissue/airspace, and the standard deviation (SD) of Lm and ATI. In the OA group, all animals demonstrated an early response (ER; RL, Rti, Raw = 183.5 +/- 7.7, 159.7 +/- 9.9, 232.5 +/- 17.2% baseline, respectively) and 11 animals showed a late response (LR; RL, Rti, Raw = 178.9 +/- 5.1, 191.3 +/- 11.5, 176.6 +/- 17.3% baseline, respectively). Neither ER nor LR were observed in the saline group.(ABSTRACT TRUNCATED AT 250 WORDS)