This study examined the effects of acute administration of bleomycin (
BLM) on lung liquid and protein exchange in anesthetized sheep prepare
d with caudal mediastinal lung lymph fistulas. Six sheep received BLM
(15 U IV) after a baseline period, while seven others were given BLM a
fter a steady state was obtained following elevation of left atrial pr
essure (P-LA) a procedure intended to minimize changes in pulmonary mi
crovascular surface area and produce high lung lymph flow (Q(L)). Plas
ma and lung lymph angiotensin converting enzyme (ACE) activities were
measured in order to independently assess the effects of BLM on pulmon
ary endothelial integrity. Q(L) rose significantly in all animals foll
owing BLM. The ratio of lymph to plasma protein concentration (C-L/C-P
) did not change in the group given BLM alone, and fell continuously d
uring the period of P-LA elevation after BLM in that group. Plasma and
lung lymph ACE activities were unchanged following BLM administration
in either group. The ultrastructure of the gas-exchanging region of l
ungs from animals in each group was examined by transmission electron
microscopy. The data suggest that acute administration of a low dose o
f BLM does not increase pulmonary microvascular permeability, but may
induce an increase in perfused pulmonary microvascular surface area re
sponsible for increased Q(L).