Protection of rats against perfluoroisobutene (PFIB)-induced pulmonary edema by curosurf and N-acetylcysteine.
Airborne exposure to lung-toxic agents may damage the lung surfactant system and epithelial and endothelial cells, resulting in a life-threatening pulmonary edema that is known to be refractory to treatment. The aim of this study was to investigate in rats (1) the respiratory injury caused by nose-only exposure to perfluoroisobutene (PFIB), and (2) the therapeutic efficacy of a treatment at 4 and/or 8 h after exposure consisting of the natural surfactant Curosurf and/or the anti-inflammatory drug N-acetylcysteine (NAC). For that purpose, the following parameters were examined: respiratory frequency (RF), lung compliance (Cdyn), airway resistance (Raw), lung wet weight (LWW), airway histopathology; and in brochoalveolar lavage (BAL) fluid, total protein, total phospholipid, cell count and differentiation, and changes in the surface tension of the BAL fluid. The mean (+/- SEM) surface tension of BAL fluid derived from PFIB-exposed (C . t = 1100-1200 mg min(-1) m(-3), approximately 1LCt50; t = 20 min) animals at 24 h following exposure (11 +/- 3 mN/m) was higher than that of unexposed rats (0.8 +/- 0.4 mN/m), reflecting damage to the surfactant system and justifying treatment with exogenous surfactant. Curosurf treatment (62.5 mg/kg i.t.) decreased pulmonary edema caused by PFIB, reflected by a decreased LWW, and decreased the amount of protein in BAL fluid. NAC treatment (1000 mmol/kg ip) inhibited the interstitial pneumonia reflected by a decreased percentage of neutrophils in the alveolar space. It was concluded that a combined treatment of Curosurf + NAC improved respiration, that is, RF and Cdyn, whereby Curosurf predominantly decreased pulmonary edema and NAC predominantly reduced the inflammatory process. A combined treatment may therefore be considered a promising therapeutic approach in early-stage acute respiratory distress caused by PFIB, although the treatment regimes need further investigation.
van Helden
Herman P M
HP
Department of Medical Countermeasures TNO Prins Maurits Laboratory, Rijswijk, the Netherlands. helden@pml.tno.nl
van de Meent
Dory
D
Oostdijk
John P
JP
Joosen
Marloes J A
MJ
van Esch
Joep H M
JH
Hammer
Arnold H
AH
Diemel
Robert V
RV
D000111:Acetylcysteine / Q000627:therapeutic use*; D000280:Administration, Inhalation; D000818:Animals; D021461:Animals, Outbred Strains; D001688:Biological Products / Q000627:therapeutic use*; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004359:Drug Therapy, Combination; D005100:Expectorants / Q000627:therapeutic use*; D005466:Fluorocarbons / Q000008:administration & dosage / Q000633:toxicity*; D019570:Inhalation Exposure; D008168:Lung / Q000187:drug effects / Q000473:pathology / Q000503:physiopathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids / Q000032:analysis / Q000627:therapeutic use*; D011506:Proteins / Q000032:analysis; D011654:Pulmonary Edema / Q000209:etiology / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017208:Rats, Wistar; D012129:Respiratory Function Tests; D013047:Specific Pathogen-Free Organisms; D013500:Surface Tension / Q000187:drug effects
D001688:Biological Products; D005100:Expectorants; D005466:Fluorocarbons; D010743:Phospholipids; D011506:Proteins; C016648:perfluoroisobutylene; C068291:poractant alfa; D000111:Acetylcysteine