Evaluation of the mechanism of decreased airway responsiveness in lambs.

In this study we investigated three possible mechanisms for the decreased airway responsiveness (AR) found in young lambs. To evaluate aerosol delivery, 6 adult sheep (9 mo-3 yr old) and 12 lambs (4-8 wk old) were challenged with aerosol (aH) and intravenous histamine (ivH). Awake animals were intubated and studied in a plethysmograph, which measured dynamic compliance (Cdyn), resistance of the lung, and functional residual capacity. AR to histamine was measured by administration of increasing concentrations of histamine until a significant change in lung mechanics occurred or until the maximum dose of histamine was given. In all six adult sheep, the response to both aH and iVH was a decrease in Cdyn. In two lambs Cdyn was decreased with both aH and ivH, in five lambs with neither, in three lambs with aH only, and in two lambs with ivH only. To examine the role of beta-adrenergic activity in determining AR, six adult sheep and six lambs received ivH and on a separate day ivH with propranolol pretreatment (p + ivH). The median effective dose of histamine that caused a reduction in Cdyn to 65% of normal saline control (ED65Cdyn) for the adult sheep given ivH was 3.60 (range 0.23-4.85) and 0.70 (range 0.49-8.0) micrograms.kg-1.min-1 for p + ivH (P = NS). The median ED65Cdyn for the six lambs was 8.0 micrograms.kg-1.min-1 for both ivH alone and p + ivH. To evaluate the role of airway smooth muscle (SM), AR to aH was quantitated in six adult sheep and six lambs, and then an open-lung biopsy was performed.(ABSTRACT TRUNCATED AT 250 WORDS)