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Decreased lung hyaluronan in a model of ARDS in the rat: effect of an inhibitor of leukocyte elastase

Authors
 CHUL MIN AHN  ;  HÅKAN SANDLER  ;  TOM SALDEEN 
Citation
 UPSALA JOURNAL OF MEDICAL SCIENCES, Vol.117(1) : 1-9, 2012 
Journal Title
 UPSALA JOURNAL OF MEDICAL SCIENCES 
ISSN
 0300-9734 
Issue Date
2012
MeSH
Animals ; Bronchoalveolar Lavage Fluid ; Disease Models, Animal* ; Enzyme Inhibitors/pharmacology* ; Hyaluronic Acid/blood ; Hyaluronic Acid/metabolism* ; Leukocyte Elastase/antagonists & inhibitors* ; Lung/enzymology ; Lung/metabolism* ; Male ; Rats ; Rats, Sprague-Dawley ; Respiratory Distress Syndrome, Adult/enzymology ; Respiratory Distress Syndrome, Adult/metabolism*
Keywords
Acute lung injury ; acute respiratory distress syndrome ; hyaluronan ; leukocyte elastase inhibitor ; pulmonary edema
Abstract
BACKGROUND: Hyaluronan (HA) is a component of the extracellular matrix in lung tissue and is normally present at low concentrations in blood. HA is rapidly cleared from blood by the liver. Increased concentrations of plasma HA have been found in patients with acute respiratory distress syndrome (ARDS). We investigated changes in HA levels in plasma, bronchoalveolar lavage fluid (BALF), and lung, and their relationship to pretreatment with a leukocyte elastase inhibitor in a rat model of ARDS. METHODS: Rats were randomly assigned to three groups: control, thrombin, and thrombin plus elastase inhibitor. By use of a radiometric assay, HA was measured in lungs, BALF, and plasma. Tissue samples from the lungs were stained for HA and examined microscopically. Liver circulation and cardiac output were monitored using radiolabeled microspheres. RESULTS: Infusion of thrombin produced a pronounced increase in wet weight to dry weight ratio, and relative lung water content. This increase was blunted by a leukocyte elastase inhibitor. A decrease in lung HA and increases in both BALF and plasma HA were found. The leukocyte elastase inhibitor counteracted not only the decrease in lung tissue HA, but also the increase in plasma HA. Histologically, there was decreased HA-staining of peribronchial and perivascular areas in the injured rat lung. Decreased liver perfusion was observed after infusion of thrombin. CONCLUSIONS: The decrease in lung HA may be involved in the development of pulmonary edema in this ARDS model, and leukocyte elastase may be one cause of this decrease. In addition, an elevated plasma HA level may be an indicator of lung injury.
Files in This Item:
T201203126.pdf Download
DOI
22283425
Appears in Collections:
1. College of Medicine (의과대학) > Dept. of Internal Medicine (내과학교실) > 1. Journal Papers
Yonsei Authors
Ahn, Chul Min(안철민)
URI
https://ir.ymlib.yonsei.ac.kr/handle/22282913/91995
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