Ultrastructural alterations in intraalveolar surfactant subtypes after experimental ischemia and reperfusion

Am J Respir Crit Care Med. 1999 Aug;160(2):718-24. doi: 10.1164/ajrccm.160.2.9809060.


Ischemia and reperfusion (I/R) result in surfactant dysfunction. Whether the impairment of surfactant is a consequence or a cause of intraalveolar edema formation is still unknown. The cumulative effects of lung perfusion, ischemic storage, and subsequent reperfusion on surfactant ultrastructure and pulmonary function were studied in a rat isolated perfused lung model. The left lungs were fixed for electron microscopy by vascular perfusion either immediately after excision (control; n = 5) or after perfusion with modified Euro-Collins solution (EC), storage for 2 h at 4 degrees C in EC, and reperfusion for 40 min (n = 5). A stereological approach was chosen to discriminate between intraalveolar surfactant subtypes of edematous regions and regions free of edema. Intraalveolar edema seen after I/R in the EC group occupied 36 +/- 6% (mean +/- SEM) of the gas exchange region as compared with control lungs (1 +/- 1%; p = 0.008). Relative intraalveolar surfactant composition showed a decrease in surface active tubular myelin (3 +/- 1 versus 12 +/- 0%; p = 0.008) and an increase in inactive unilamellar forms (83 +/- 2 versus 64 +/- 5%; p = 0.008) in the EC group. These changes occurred both in edematous (tubular myelin, 3 +/- 1%; unilamellar forms, 88 +/- 6%) and in nonedematous regions (tubular myelin, 4 +/- 3%; unilamellar forms, 77 +/- 5%). The ultrastructural changes in surfactant were associated with an increase in peak inspiratory pressure during reperfusion. In conclusion, surfactant alterations seen after I/R are not directly related to the presence of edema fluid in the alveoli. Disturbances in intraalveolar surfactant after I/R are not merely the result of inactivation due to plasma protein leakage but may instead be responsible for an increased permeability of the blood-air barrier, resulting in a vicious cycle of intraalveolar edema formation and progressing surfactant impairment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blood-Air Barrier / physiology
  • Capillary Permeability / physiology
  • Ischemia / pathology*
  • Lung / blood supply*
  • Lung / pathology
  • Male
  • Microscopy, Electron
  • Organ Preservation
  • Pulmonary Alveoli / blood supply*
  • Pulmonary Alveoli / pathology
  • Pulmonary Edema / pathology
  • Pulmonary Gas Exchange / physiology
  • Pulmonary Surfactants / classification
  • Pulmonary Surfactants / ultrastructure*
  • Rats
  • Rats, Sprague-Dawley
  • Reperfusion Injury / pathology*


  • Pulmonary Surfactants