Effects of edema on small airway narrowing

Numerous mediators of inflammation have been demonstrated to cause airway microvascular fluid and protein extravasation. That fluid extravasation results in airway wall edema leading to airway narrowing and enhanced reactivity has not been confirmed. In anesthetized, ventilated sheep (n = 30), airway vascular fluid extravasation was induced by infusing bradykinin (10(-6) M) through a cannulated, blood-perfused bronchial artery. Airway wall edema and luminal narrowing were determined morphometrically. Airway reactivity to methacholine (MCh; 10 microg/ml, intrabronchial artery) was determined by measuring conducting airway resistance (Raw) by forced oscillation. Raw measurements were made and lung lobes were excised and quick frozen before or after a 1-h bradykinin infusion. In 10 airways per lobe (range 0.2- to 2.0-mm relaxed diameter), wall area occupied 32 +/- 2% (SE) of the total normalized airway area (n = 9). Bradykinin infusion increased wall area to 42 +/- 5% (P = 0.02); luminal area decreased by <5%; and smooth muscle perimeter, a measure of smooth muscle constriction, was not altered (n = 5). Raw showed no change from baseline (1.4 +/- 0.4 cmH2O . l-1 . s) after bradykinin infusion (n = 10). During MCh challenge, Raw increased by 3.2 +/- 04 cmH2O . l-1 . s, and this change did not differ after administration of bradykinin. MCh challenge caused similar decreases in smooth muscle perimeter (10%) and luminal area (72 vs. 68%) before and after bradykinin infusion. However, the time constant of recovery of Raw from MCh constriction was increased from control (40 +/- 3 s) to 57 +/- 10 s after bradykinin infusion (P = 0.03). When lung lobes were excised at the same time after MCh challenge was terminated (n = 5), luminal area was greater before bradykinin infusion than after (86 vs. 78%; P = 0.007), as was smooth muscle perimeter. The results of this study demonstrate that airway wall edema limits relaxation after induced constriction rather than enhancing constriction.