Am. J. Respir. Crit. Care Med., Volume 160, Number 2, August 1999, 718-724

Ultrastructural Alterations in Intraalveolar Surfactant Subtypes after Experimental Ischemia and Reperfusion

MATTHIAS OCHS, ILIJA NENADIC, ANTONIA FEHRENBACH, JOHANNES M. ALBES, THORSTEN WAHLERS, JOACHIM RICHTER, and HEINZ FEHRENBACH

Division of Electron Microscopy, Department of Anatomy, University of Göttingen, Göttingen, Germany; Division of Thoracic and Cardiovascular Surgery, Medical School Hannover, Hannover, Germany; and Institute of Pathology, University Clinics Carl Gustav Carus, TU Dresden, Dresden, Germany

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° 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.

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