Methods: Female Wistar rats were divided into 4 groups: BD (submitted to BD for 6 h), sham (false-operated), E2-T0 (treated with E2 immediately after BD; 50 μg/ml, 2 ml/h), and E2-T3 (treated with E2 after 3 h of BD; 50 μg/ml, 2 ml/h). Lung edema, hemorrhage, and leukocyte infiltration were analyzed. Adhesion molecules were evaluated and analysis of NO synthase gene and protein expression was performed using RT-PCR and immunohistochemistry, respectively. Release of chemokines and matrix degradation in the lungs were analyzed.
Results: BD increased leukocyte infiltration, as shown by intravital microscopy (P=0.017), bronchoalveolar lavage cell count (P=0.016), the release of inflammatory mediators (P=0.02), and expression of adhesion molecules. BD also increased microvascular permeability and the expression and activity of MMP-9 in the lungs. E2 treatment reduced leukocyte infiltration, especially in the E2-T3 group, release of inflammatory mediators, adhesion molecules, and MMP activity in the lungs.
Conclusions: E2 treatment was successful in controlling the lung inflammatory response in females submitted to BD. Our results suggest that E2 directly decreases the release of chemokines, restraining cell traffic into the lungs. Thus, E2 has a therapeutic potential, and its role in improving donor lung quality should be explored further.