Intravascular FC-77 attenuates phorbol myristate acetate-induced acute lung injury in isolated rat lungs.
OBJECTIVE
To evaluate whether intravascular Fluorinert (FC-77) attenuates phorbol myristate acetate (PMA)-induced acute lung injury in rats.


METHODS
Randomized, controlled animal study.


METHODS
Animal care facility procedure room in a medical center.


METHODS
Thirty-six adult male Sprague-Dawley rats each weighing 250-350 g.


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Chang
Hung
H
Department of Surgery, Tri-Service General Hospital, Taipei, Taiwan, Republic of China.
Li
Min-Hui
MH
Chen
Chien-Wen
CW
Yan
Horng-Chin
HC
Huang
Kun-Lun
KL
Chu
Shi-Jye
SJ
D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects; D002273:Carcinogens / Q000037:antagonists & inhibitors* / Q000633:toxicity; D004195:Disease Models, Animal; D005466:Fluorocarbons / Q000627:therapeutic use*; D008297:Male; D009929:Organ Size / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D012128:Respiratory Distress Syndrome / Q000139:chemically induced / Q000473:pathology / Q000517:prevention & control*; D013755:Tetradecanoylphorbol Acetate / Q000037:antagonists & inhibitors* / Q000633:toxicity; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
D002273:Carcinogens; D005466:Fluorocarbons; D014409:Tumor Necrosis Factor-alpha; C429307:fluorocarbon 77; D009195:Peroxidase; D013755:Tetradecanoylphorbol Acetate