Triiodo-L-thyronine rapidly stimulates alveolar fluid clearance in normal and hyperoxia-injured lungs.
BACKGROUND
Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na, K-ATPase and other ion transport proteins.


OBJECTIVE
In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T(3)).


METHODS
AFC was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% bovine serum albumin solution with fluorescein-labeled albumin tracer and measuring the change in fluorescein isothiocyanate-albumin concentration over time.


RESULTS
Systemic treatment with intraperitoneal injections of T(3) for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T(3)-treated rats had higher Na, K-ATPase hydrolytic activity. T(3) (10(-6) M), but not reverse T(3) (3,3',5' triiodo-L-thyronine), applied to the alveolar space increased AFC by 31.8% within 1.5 hours. A 61.5% increase in AFC also occurred by airspace instillation of T(3) in ex vivo isolated lungs, suggesting a direct effect of T(3) on the alveolar epithelium. Exposure of rats to an oxygen concentration of greater than 95% for 60 hours increased wet-to-dry lung weights and decreased AFC, whereas the expression of thyroid receptor was not markedly changed. Airspace T(3) rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury.


CONCLUSIONS
Airspace T(3) rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.
Bhargava
Maneesh
M
Division of Pulmonary, Allergy, Critical Care, and Sleep, Department of Medicine, University of Minnesota Medical School, Minneapolis, Minnesota 55455, USA.
Runyon
Marie R
MR
Smirnov
Dmitri
D
Lei
Jianxun
J
Groppoli
Thomas J
TJ
Mariash
Cary N
CN
Wangensteen
O Douglas
OD
Ingbar
David H
DH
D000818:Animals; D002478:Cells, Cultured; D007274:Injections, Intraperitoneal; D008297:Male; D011654:Pulmonary Edema / Q000188:drug therapy*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D020545:Respiratory Mucosa / Q000166:cytology / Q000187:drug effects; D000254:Sodium-Potassium-Exchanging ATPase / Q000378:metabolism; D014284:Triiodothyronine / Q000494:pharmacology*
D014284:Triiodothyronine; D000254:Sodium-Potassium-Exchanging ATPase