DISTRIBUTION OF AIRWAY NARROWING DURING HYPERPNEA-INDUCED BRONCHOCONSTRICTION IN GUINEA-PIGS

Increasing minute ventilation of dry gas shifts the principal burden of respiratory heat and water losses from more proximal airway to airways farther into the lung. If these local thermal transfers determine the local stimulus for bronchoconstriction, then increasing minute ventilation of dry gas might also extend the zone of airway narrowing farther into the lung during hyperpnea-induced bronchoconstriction (HIB). We tested this hypothesis by comparing tantalum bronchograms in tracheostomized guinea pigs before and during bronchoconstriction induced by dry gas hyperpnea, intravenous methacholine, and intravenous capsaicin. In eight animals subjected to 5 min of dry gas isocapnic hyperpnea [tidal volume (V(T)) = 2-5 ml, 150 breaths/min], there was little change in the diameter of the trachea or the main stem bronchi up to 0.75 cm past the main carina (zone 1). In contrast, bronchi from 0.75 to 1.50 cm past the main carina (zone 2) narrowed progressively at all minute ventilations ≥300 ml/min (V(T) = 2 ml). More distal bronchi (1.50-3.10 cm past the main carina; zone 3) did not narrow significantly until minute ventilation was raised to 450 ml/min (V(T) = 3 ml). The estimated V(T) during hyperpnea needed to elicit a 50% reduction in airway diameter was significantly higher in zone 3 bronchi [4.3 ± 0.8 (SD) ml] than in zone 2 bronchi (3.5 ± 1.1 ml, P < 0.012). In marked contrast, the diameter changes in zone 2 and 3 bronchi were always similar when intravenous methacholine was given [estimated dose for 50% reduction in airway diameter (ED50) was 3.5 ± 2.9 vs. 2.8 ± 3.3 x 10-8 mol, respectively, P = NS] or when endogenous tachykinins were released by intravenous capsaicin (ED50 = 13.6 ± 9.1 vs. 14.3 ± 12.6 μg/kg, respectively, P = NS). These data suggest that increasing minute ventilation results in more severe HIB both by increasing the severity of zone 2 bronchial narrowing and by recruiting more distal zone 3 bronchi into the bronchoconstrictor response. Furthermore these results are not explained by axially distributed differences in the ability of airway smooth muscle to narrow airway lumen or by differences in sensory nerve or tachykinin receptor function between zone 2 and 3 bronchi. These results support the hypothesis that local heat/water exchanges determine the severity of local airway narrowing induced by dry gas hyperpnea.