Persistent increased lung response to methacholine after normobaric hyperoxia in rabbits

This study was performed to determine the occurrence and time course of airway hyperreactivity following exposure to normobaric hyperoxia. Twenty-six rabbits were studied. Twelve served as control (group 1), and 14 were exposed to normobaric hyperoxia (FiO2 > or = 95%) for 48 h: 9 rabbits (group 2) were studied after 1 day of recovery in room air and 5 (group 3) after 7 days. The rabbits were anesthetized, curarized and artificially ventilated. Respiratory resistance (Rrs) and elastance (Ers) and their respective changes induced by cumulative doses of aerosolized methacholine were assessed by the multiple linear regression analysis of airway pressure, tidal flow and volume. Weight-specific Rrs and Ers were significantly higher in group 2 (respectively, 87.7 +/- 6.5 cmH2O.L-1.sec.kg and 1100.2 +/- 87.1 cmH2O.L-1.kg, mean +/- SEM) than in group 1 (respectively, 65.2 +/- 3.2 cmH2O.L-1.sec.kg and 904.4 +/- 49.7 cmH2O.L-1.kg (P < 0.05)), but were not different from group 3 (79.4 +/- 7.9 cmH2O.L-1.sec.kg and 952.3 +/- 125.0 cmH2O.L-1.kg, respectively). The dose of methacholine required to increase Rrs by 50% (PDRrs50) was significantly lower in both treated groups: 0.37 +/- 0.11 mg in group 2 and 0.51 +/- 0.19 mg in group 3 vs 2.07 +/- 0.51 mg in group 1 (P < 0.05)). PDErs50 was significantly lower in group 2 (0.45 +/- 0.15 mg) and 3 (0.75 +/- 0.43 mg) compared with controls (1.11 +/- 0.26 mg (P < 0.05)). These results show that hyperoxia induces an increase in Rrs and Ers, and airway hyperreactivity in the rabbit. The latter is prolonged beyond the immediate post-exposure period.