Sulforhodamine B interacts with albumin to lower surface tension and protect against ventilation injury of flooded alveoli

J Appl Physiol (1985). 2015 Feb 1;118(3):355-64. doi: 10.1152/japplphysiol.00818.2014. Epub 2014 Nov 20.

Abstract

In the acute respiratory distress syndrome, alveolar flooding by proteinaceous edema liquid impairs gas exchange. Mechanical ventilation is used as a supportive therapy. In regions of the edematous lung, alveolar flooding is heterogeneous, and stress is concentrated in aerated alveoli. Ventilation exacerbates stress concentrations and injuriously overexpands aerated alveoli. Injury degree is proportional to surface tension, T. Lowering T directly lessens injury. Furthermore, as heterogeneous flooding causes the stress concentrations, promoting equitable liquid distribution between alveoli should, indirectly, lessen injury. We present a new theoretical analysis suggesting that liquid is trapped in discrete alveoli by a pressure barrier that is proportional to T. Experimentally, we identify two rhodamine dyes, sulforhodamine B and rhodamine WT, as surface active in albumin solution and investigate whether the dyes lessen ventilation injury. In the isolated rat lung, we micropuncture a surface alveolus, instill albumin solution, and obtain an area with heterogeneous alveolar flooding. We demonstrate that rhodamine dye addition lowers T, reduces ventilation-induced injury, and facilitates liquid escape from flooded alveoli. In vitro we show that rhodamine dye is directly surface active in albumin solution. We identify sulforhodamine B as a potential new therapeutic agent for the treatment of the acute respiratory distress syndrome.

Keywords: acute respiratory distress syndrome; alveolar mechanics; rhodamine; surface tension; ventilation injury.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Albumins / metabolism*
  • Animals
  • Lung Injury / drug therapy*
  • Lung Injury / metabolism
  • Male
  • Pulmonary Alveoli / drug effects*
  • Pulmonary Alveoli / metabolism
  • Pulmonary Edema / drug therapy*
  • Pulmonary Edema / metabolism
  • Pulmonary Gas Exchange
  • Rats
  • Rats, Sprague-Dawley
  • Respiration / drug effects
  • Respiration, Artificial / methods
  • Respiratory Distress Syndrome / drug therapy
  • Respiratory Distress Syndrome / metabolism
  • Rhodamines / pharmacology*
  • Surface Tension / drug effects*

Substances

  • Albumins
  • Rhodamines
  • rhodamine WT
  • lissamine rhodamine B