Efficacy of Curosurf in a rat model of acute respiratory distress syndrome.
Curosurf, a natural lung surfactant, is considered a potential candidate for improving the treatment of acute respiratory distress syndrome (ARDS). To investigate this in a rat model of early-stage ARDS, Curosurf (62.5, 125 or 250 mg x kg(-1)) was administered by intratracheal bolus at 10 or 24 h following an intratracheal lipopolysaccharide (LPS; 1.6 mg x kg(-1)) challenge. Survival, respiratory frequency (fR), lung wet weight (LWW), total protein and cell differentiation in bronchoalveolar lavage fluid (BALF) were assessed. Curosurf treatment at 10 h after LPS challenge resulted in 100% survival at both 62.5 and 125 mg x kg(-1); at a dose of 250 mg x kg(-1) administered at 10 h after LPS, 1 out of 6 animals died. At a dose of 125 mg x kg(-1) Curosurf administered at 24 h after LPS, 1 out of 6 animals died. In contrast, only 35% of animals survived when not treated with Curosurf. Curosurf treatment resulted in an improved fR and in a significantly decreased LWW, total protein and number of polymorphonuclear cells in BALF. In conclusion, Curosurf treatment improved respiratory frequency and decreased mortality, pulmonary oedema and inflammation. As the decreased mortality was observed in spontaneously breathing nonoxygenated animals, the results cannot be extrapolated to human artificially ventilated acute respiratory distress syndrome patients with the expectation of a decreased mortality. The results suggest, however, that Curosurf may be an important therapeutic measure in early-stage acute respiratory distress syndrome.
van Helden
H P
HP
TNO Prins Maurits Laboratory, Research Group Pharmacology, Rijswijk, The Netherlands.
Kuijpers
W C
WC
Langerwerf
P E
PE
Langen
R C
RC
Haagsman
H P
HP
Bruijnzeel
P L
PL
D000704:Analysis of Variance; D000818:Animals; D001688:Biological Products; D001985:Bronchial Provocation Tests; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry / Q000166:cytology; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D007278:Injections, Spinal; D008070:Lipopolysaccharides / Q000494:pharmacology; D008168:Lung / Q000473:pathology; D008297:Male; D009929:Organ Size / Q000187:drug effects; D010743:Phospholipids; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D051381:Rats; D017208:Rats, Wistar; D012016:Reference Values; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D012129:Respiratory Function Tests; D015996:Survival Rate; D016896:Treatment Outcome
D001688:Biological Products; D008070:Lipopolysaccharides; D010743:Phospholipids; D011663:Pulmonary Surfactants; C068291:poractant alfa