The influence of pulmonary vascular congestion on the response of the airwa
ys and lung tissue to low doses of inhaled methacholine (MCh) was studied b
y inflating a balloon catheter in the left atrium of the heart in six pigle
ts, with an additional five piglets serving as control animals. Congestion
alone resulted in small increased in baseline airway (Raw) (14.6 +/- 3.7%)
and tissue (Rti) resistance (8.1 +/- 6.5%). Low-dose inhaled MCh (0.3 mg/ml
) increased Raw and Rti in the control group by 10.8 +/- 10.3% and 42.2 +/-
29.5%, respectively. The increase in Raw with MCh in the presence of vascu
lar engorgement was significantly greater (67.8 +/- 18.9%) but the increase
in Rti (38.1 +/- 13.2%) was similar to that seen in the control group. Mor
phometric measurements were performed on transverse sections of large and s
mall airways from nine additional piglets (three congested only, three MCh
only, and three congestion plus MCh). The thickness of the inner airway wal
l was similar in all groups. Compared with MCh only piglets, the thickness
of the outer airway wall (between the outer border of the smooth muscle and
the surrounding lung parenchyma) was increased (p < 0.05) in engorged only
and engorged plus MCh piglets. Compared with MCh only and engorgement only
, the amount of airway smooth muscle shortening was greater (p < 0.05) in a
ll airway size groups in piglets that underwent engorgement plus MCh challe
nge. The results of this study demonstrate that pulmonary vascular engorgem
ent, induced by increased left atrial pressure, selectively enhances the ai
rway, but not the parenchymal, response to inhaled MCh. These changes are a
ssociated with increased thickness of the outer airway wall in response to
vascular congestion, suggesting that uncoupling of the mechanical interdepe
ndence between the airway smooth muscle and the lung parenchyma may have oc
curred. Mechanical uncoupling may reduce the load opposing smooth muscle sh
ortening resulting in increased airway narrowing in response to low doses o
f inhaled methacholine.