TIME COURSE OF BRONCHOCONSTRICTION INDUCED BY DRY GAS HYPERPNEA IN GUINEA-PIGS

We examined the effects of hyperpnea duration and abrupt changes in inspired gas heat and water content on the magnitude and time course of hyperpnea-induced bronchoconstriction (HIB) in anesthetized mechanically ventilated male Hartley guinea pigs. In 12 animals subjected to 5, 10, and 15 min (random order) of dry gas isocapnic hyperpnea [tidal volume (VT) 4-6 ml, 150 breaths/min) followed by quiet breathing of humidified air (VT 2-3 ml, 60 breaths/min), severe bronchoconstriction developed only after the cessation of hyperpnea; the magnitude of respiratory system resistance (Rrs) increased with the duration of dry gas hyperpnea [peak Rrs 1.0 +/- 0.2, 1.8 +/- 0.3, and 2.3 +/- 0.3 (SE) cmH2O.ml-1.s, respectively]. Seven other guinea pigs received, in random order, 10 min of warm humidified gas hyperpnea, 10 min of room temperature dry gas hyperpnea, and 5 min of dry gas hyperpnea immediately followed by 5 min of warm humidified gas hyperpnea. After each hyperpnea period, the animal was returned to quiet breathing of humidified gas. Rrs rose appreciably after the 10 min of dry and 5 min of dry-5 min of humidified hyperpnea challenges (peak Rrs 1.3 +/- 0.2 and 0.7 +/- 0.2 cmH2O.ml-1.s, respectively) but not after 10 min of humidified hyperpnea (0.2 +/- 0.04 cmH2O.ml-1.s). An additional five animals received 10 min of room temperature dry gas hyperpnea followed by quiet breathing of warm humidified air and 10 min of room temperature dry gas hyperpnea followed by 30 min of warm humidified gas hyperpnea in random order. The continued humid gas hyperpnea fully suppressed the expression of bronchoconstriction seen after the 10 min of dry gas hyperpnea (peak Rrs 1.2 +/- 0.2 vs. 0.5 +/- 0.1 cmH2O.ml-1.s, quiet recovery vs. continued hyperpnea, respectively). Inspection of the Rrs values during the 10-min periods of room temperature dry gas hyperpnea from all the above experiments revealed a small but significant rise in resistance (P < 0.01) that was not evident during warm humidified gas hyperpnea. Additional studies in 16 animals confirm that neither propranolol (1 mg/kg iv) nor elevated inspired O2 tension during hyperpnea (95% O2) and recovery (50% O2) significantly alters the magnitude of HIB in guinea pigs. In all, these data suggest that nonthermal effects of hyperpnea per se effectively inhibit bronchoconstriction elicited by dry gas hyperpnea in the guinea pig.