Published ahead of print on June 12, 2008, doi:10.1164/rccm.200709-1429OC Am. J. Respir. Crit. Care Med., Volume 178, Number 5, September 2008, 506-512 A more recent version of this article appeared on September 1, 2008
Submitted on September 26, 2007 Triiodo-l-thyronine Rapidly Stimulates Alveolar Fluid Clearance in Normal & Hyperoxia Injured LungsManeesh Bhargava1,1 Divisions of Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota Medical School, Minneapolis, MN, USA, 2 Division of Endicrinology, University of Minnesota Medical School, Minneapolis, MN, USA, 3 Departments of Medicine and Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA, 4 Divisions of Pulmonary, Allergy, Critical Care, and Sleep, University of Minnesota Medical School, Minneapolis, MN, USA; Departments of Medicine and Integrative Biology and Physiology, University of Minnesota Medical School, Minneapolis, MN, USA * To whom correspondence should be addressed. 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 is stimulated by 3,3',5 triiodo-l-thyronine (T3). Methods and Measurements: Alveolar fluid clearance (AFC) was measured in in situ ventilated lungs and ex vivo isolated lungs by instilling isosmolar 5% BSA solution with fluorescein-labeled albumin tracer and measuring the change in FITC-albumin concentration over time. Main Results: Systemic treatment with intraperitoneal injections of T3 for 3 consecutive days increased AFC by 52.7% compared to saline injected control rats. Membranes prepared from alveolar epithelial cells from T3 treated rats had higher Na,K-ATPase hydrolytic activity. T3 (10-6M), 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 > 95% oxygen for 60 hours increased wet to dry lung weights, decreased AFC while the expression of thyroid receptor was not markedly changed. Conclusions: Airspace T3 rapidly restored the AFC in rat lungs with hyperoxia induced lung injury. In summary, airspace T3 rapidly stimulates alveolar fluid clearance by direct effects on the alveolar epithelium in rat lungs with and without lung injury. Key words: Alveolar fluid clearance; ARDS; pulmonary edema; alveolar NA,K-ATPase; alveolar epithelium
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