Changes in lung fluid volumes and hyaluronan clearance were measured i
n six awake sheep during increased microvascular permeability induced
by pulmonary air embolism (AE). After a 1- to 2-h baseline, filtered r
oom air was infused through a proximal port of a Swan-Ganz catheter fo
r 2 h at a rate sufficient to double pulmonary vascular resistance. Th
e air infusion was discontinued, and the sheep were monitored for an a
dditional 2 h (recovery). Lung lymph flow and protein flux increased d
uring air infusion and continued to increase during recovery. During A
E, lymph-to-plasma ratio for albumin decreased while lymph-to-plasma r
atio for large protein remained the same. This would suggest that both
microvascular pressure and microvascular permeability increase during
AE. Protein clearance increased similarly for all protein sizes durin
g AE and recovery. After 2 h of recovery, interstitial and extravascul
ar volumes were elevated with no change in cellular volume. The volume
of the interstitium available to albumin was more than twice control.
The fraction of the interstitium that excludes albumin was calculated
to be 0.32 +/- 0.04, with a 51% reduction in absolute excluded volume
2 h after AE. Clearance of hyaluronan by the lymphatics (normalized t
o baseline) increased 6- to 10-fold during and after AE. It was estima
ted that <2% of the total hyaluronan in the lung would be cleared in 2
4 h under baseline conditions. This amount increased to approximately
11% under AE conditions and approximately 15% under recovery condition
s. Changes in lung fluid volumes and protein clearance indicate increa
sed microvascular permeability 2 h after AE. However, other factors, s
uch as clearance of hyaluronan from the interstitium, may have influen
ced the substantial reduction in albumin exclusion in the lung interst
itium.