Intravascular FC-77 attenuates phorbol myristate acetate-induced acute lung injury in isolated rat lungs

Abstract

To evaluate whether intravascular Fluorinert (FC-77) attenuates phorbol myristate acetate (PMA)-induced acute lung injury in rats. Randomized, controlled animal study. Animal care facility procedure room in a medical center. Thirty-six adult male Sprague-Dawley rats each weighing 250-350 g. PMA (2 microg/kg) was injected into lung perfusate and induced acute lung injury. Different doses of FC-77 were given before PMA administration. The isolated rat lungs were randomly assigned to two control groups (saline and 1% FC-77 only) and four PMA groups (PMA, 0.1% FC-77 + PMA, 0.5% FC-77+PMA, and 1% FC-77+PMA); each condition was maintained for 60 mins. The extent of acute lung injury was assessed by microvascular permeability (measured using the capillary filtration coefficient), lung weight gain, wet lung-to-body weight ratio, pulmonary arterial pressure, and protein concentration of the bronchoalveolar lavage fluid. The concentration of tumor necrosis factor-alpha in lung perfusate was determined. Parts of the right lung were excised for myeloperoxidase and malondialdehyde measurements, whereas the rest was examined for histopathological changes. PMA produced a significant increase in the capillary filtration coefficient, lung weight gain, wet lung-to-body weight ratio, pulmonary arterial pressure, and protein concentration of the bronchoalveolar lavage fluid. Tumor necrosis factor-alpha in lung perfusate and myeloperoxidase and malondialdehyde in lung tissue were also significantly increased. In addition, the pathologic picture showed increased neutrophil infiltration in lung tissues. In contrast, pretreatment with intravascular FC-77 significantly attenuated these variables in a dose-dependent manner compared with the PMA group. Intravascular FC-77 significantly ameliorated acute lung injury induced by PMA in rats in a dose-dependent manner. The protective mechanism may act, in part, by decreasing neutrophil infiltration, inhibiting proinflammatory cytokine production, and preventing the release of free radicals.