Hypothermia is intentionally imposed during the harvesting of lungs for tra
nsplantation. The aim of this study was to investigate the fluid balance al
terations in rat lung preparations exposed to hypothermic perfusion. Loweri
ng perfusate temperature from 37 degreesC to values between 27 and 7 degree
sC caused an immediate, marked pulmonary hypertension and vasoconstriction
accompanied by rapid development of pulmonary edema (+1.15 g, or similar to
90%, gain in lung weight within 5 min). However, on rewarming, vasoconstri
ction was immediately reversed. Edema was resolved, but along a two-compone
nt time course: an immediate reduction of lung weight on rewarming (t(1/2)
of 0.5 min) that mirrored the recovery of pulmonary artery pressure and vas
oconstriction, and also a slower pressure-independent component of recovery
(t(1/2) of 3.5 min). Ouabain (300 muM) markedly inhibited the lung's abili
ty to recover from edema, indicating that fluid clearance from lung tissue
was the result of activation of ouabain-sensitive (Na+,K+)-ATPase pump. Res
ults could not be explained by vascular or airspace injury as lung sections
from hypothermic lungs appeared normal. The findings indicate that hypothe
rmia induces pulmonary edema formation, which can be rapidly cleared upon r
ewarming by activation of ouabain -sensitive (Na+,K+)-ATPase pump. Thus, im
paired fluid clearance from lung extravascular spaces may be a critical fac
tor limiting gas exchange in transplanted lungs exposed to hypothermia.