Surfactant pretreatment ameliorates ischemia-reperfusion injury of the lung

Abstract

To investigate whether surfactant pretreatment provides lung protection in an animal model of lung ischemia-reperfusion injury (LIRI). Male Sprague-Dawley rats (n=100) were randomised to receive intratracheally administered surfactant or no pretreatment. One hour thereafter, animals underwent 120min of warm ischemia of the left lung, or were sham-operated. A third group served as healthy untreated controls. Animals were killed on day 1, 3 or 7. Blood gas values were measured and lung compliance was recorded. Broncho-alveolar lavage fluid (BALf) was obtained to assess the amount of alveolar protein, the ratio of small to large aggregate surfactant phospholipids (SA/LA ratio), and leukocyte infiltration (granulocytes, macrophages and lymphocytes, measured by Flow Cytometry). LIRI resulted in a mortality rate of 17% and significantly decreased lung compliance and PaO(2) (day 1 and 3 P<0.001, day 7 P<0.05) as compared to sham-operated and healthy controls. On day 1 more protein was present in the alveoli of ischemic lungs (P<0.001) than in sham-operated and healthy controls. Furthermore, LIRI resulted in an increased SA/LA ratio in the left lung on day 1 (P<0.05) and caused infiltration of granulocytes (day 1, 3 and 7 (P<0.01)), macrophages (day 3 (P<0.05) and 7 (P<0.01) and lymphocytes (day 3 and 7 (P<0.01)) in the BALf as compared to sham-operated and healthy controls. Surfactant pretreatment improved survival, lung compliance (day 3 P<0.001) and PaO(2) (day 1, 3 (P<0.01 and 7 (P<0.05)). It also reduced protein leakage (P<0.05) and prevented an increase in the SA/LA ratio (P<0.01). Although the number of macrophages and granulocytes in the BALF was increased on day 1 and 3 (P<0.01) after surfactant pretreatment as compared to all other groups, the number of lymphocytes was reduced on day 3 (P<0.05). The present study shows that surfactant pretreatment enhances recovery of lung function and lung mechanics after LIRI, resulting in normal parameters from day 3 onwards. Surfactant pretreatment in this LIRI model may provide useful information to improve donor lung function after lung transplantation.