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Triiodo-L-thyronine Rapidly Stimulates Alveolar Fluid Clearance in Normal and Hyperoxia-injured Lungs

¹ Division of Pulmonary, Allergy, Critical Care, and Sleep, and ² Division of Endocrinology, Department of Medicine, and ³ Department of Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, Minnesota

Correspondence and requests for reprints should be addressed to David H. Ingbar, M.D., University of Minnesota School of Medicine, Pulmonary MMC 276, 420 Delaware Street SE, Minneapolis, MN 55455. E-mail: ingba001{at}umn.edu

Rationale: Edema fluid resorption is critical for gas exchange and requires active epithelial ion transport by Na,K-ATPase and other ion transport proteins.

Objectives: In this study, we sought to determine if alveolar fluid clearance (AFC) is stimulated by 3,3',5 triiodo-L-thyronine (T₃).

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.

Measurements and Main Results: Systemic treatment with intraperitoneal injections of T₃ for 3 consecutive days increased AFC by 52.7% compared with phosphate-buffered saline-injected control rats. Membranes prepared from alveolar epithelial cells from T₃-treated rats had higher Na,K-ATPase hydrolytic activity. T₃ (10^–6 M), but not reverse T₃ (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 T₃ in ex vivo isolated lungs, suggesting a direct effect of T₃ 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 T₃ rapidly restored the AFC in rat lungs with hyperoxia-induced lung injury.

Conclusions: Airspace T₃ rapidly stimulates AFC by direct effects on the alveolar epithelium in rat lungs with and without lung injury.

Key Words: alveolar fluid clearance • acute respiratory distress syndrome • alveolar Na,K-ATPase • type 2 cell • thyroid hormone

AT A GLANCE COMMENTARY Scientific Knowledge on the Subject Alveolar fluid clearance is decreased in conditions associated with pulmonary edema. Stimulation of pulmonary edema clearance might improve outcomes in lung injury and acute respiratory distress syndrome. What This Study Adds to the Field 3,3',5 Triiodo-L-thyronine (T3) stimulates alveolar fluid clearance. Airspace T3 rapidly restores the decreased alveolar fluid clearance in rat lungs with hyperoxia-induced lung injury.