Aminophylline reduces air-flow-induced constriction in the canine lung periphery

We examined the effect of aminophylline on air-flow-induced constriction in the canine lung periphery. A wedged bronchoscope technique was used to measure airway wall temperature (Taw) and collateral resistance (Rcs) before and after air flow was increased from a baseline flow of 200 to 500, 1,000, 1,500, or 2,000 ml/min for 2-min periods. When a sublobar segment was challenged with dry air, Taw fell during the challenge (p<0.05) and Rcs increased 5 min postchallenge (p<0.01). Pretreatment with aminophylline (20 mg/kg) reduced the fall in Taw by 31% and reduced the increase in Rcs by 53%. Aminophylline did not significantly affect either the concentrations of PGD₂, TxB₂, and histamine or the cell numbers and profiles obtained by bronchoalveolar lavage performed 5 min postchallenge. However, trends were consistent with the decreased physiologic responses observed. Finally, aminophylline proved ineffective in reducing the constrictor response of peripheral lung challenged directly with aerosolized histamine or PGD₂. Because preaminophylline and postaminophylline peripheral lung sensitivity (as assessed by the ratio ΔRcs/ΔTaw) were not significantly different, we conclude that aminophylline attenuates physiologic responses by reducing the strength of the stimulus. Aminophylline could do this by facilitating the replacement of heat and water removed during dry air challenge by increasing bronchial or pulmonary blood flow, or by reducing heat and water loss via changes in mucosal permeability.