IN-VIVO, IN-VITRO CORRELATION OF ACETYLCHOLINE AIRWAY RESPONSIVENESS IN SENSITIZED GUINEA-PIGS - THE ROLE OF MODIFIED EPITHELIAL FUNCTIONS

Many attempts have failed to correlate in vivo airway responsiveness w ith in Vitro airway smooth muscle functions. We have reexamined this r elation by taking account of airway epithelial functions in guinea pig s sensitized with inhaled ovalbumin (OA). In vivo responses were asses sed by the provocative concentration of acetylcholine (ACh) required t o double the airway opening pressure (PC200) under mechanical ventilat ion. In vitro responses were measured in a perfused whole-tracheal pre paration. The negative logarithm of the molar concentration of ACh req uired to produce a 10% reduction in diameter was calculated both for e pithelial-side stimulation (PC10(in) and for serosal-side stimulation (PC10(out)). OA-sensitized guinea pigs showed significantly smaller lo g PC200 than control animals (0.51 +/- 0.07 and 0.81 +/- 0.10, respect ively, p < 0.01). In in vitro study, there were variable differences i n PC10(in) and PC10(out)) in each animal. The difference in sensitivit y between epithetial- and serosal-side stimulation (PC10(in-out)) show ed a significant correlation in PC10(in) (r = 0.82, n = 9, p < 0.01) b ut not to PC10(out) (r = 0.39, p > 0.1), indicating that the variation in PC10(in-out) resulted from the changes in PC10(in). For in vivo-in vitro correlation, log PC200 correlated significantly with PC10(in) ( r = 0.68, n = 9, p < 0.05) but not with PC10(out)) (r = 0.18, p > 0.1) . These results indicate that the sensitization by inhalation of OA pr oduces increased airway responsiveness to ACh in vivo and that this ai rway responsiveness may be related, at least in part, to the altered a irway epithelial functions.