The pre-term guinea-pig: a model for the study of neonatal lung disease.
1. Research into the pathogenesis of acute and chronic neonatal lung disease has been hampered by the lack of a suitable small-animal model of prematurity. We describe such a model that has been developed and validated in the guinea-pig. 2. Pre-term guinea-pigs delivered by Caesarian section at 65 days gestation (normal gestation 68 days) exhibited transient respiratory distress. The survival of pre-term animals was lower than that of term animals after exposure to 95% O2 (pre-term 42% versus term 79% at 96 h, P less than 0.05). 3. Pulmonary histology in pre-term animals exposed to both 21% O2 and 95% O2 revealed evidence of acute lung injury with atelectasis, pulmonary oedema, fibrin deposition and inflammatory cell infiltration. No evidence of lung injury was observed in term animals exposed to 21% O2, whereas those exposed to 95% O2 showed a similar, but less pronounced, injury to that seen in pre-term pups. 4. The protein concentration in bronchoalveolar lavage fluid was similar in pre-term and term animals exposed to 95% O2, but neutrophil numbers in bronchoalveolar lavage fluid tended to be greater in pre-term pups. 5. Elastase-like activity, measured against succinyl-1-trialanine p-nitroanilide, was higher in bronchoalveolar lavage fluid from control pre-term animals compared with that from control term animals. Exposure to 95% O2 increased the elastase-like activity significantly in both groups. The majority of the elastase-like activity was EDTA-sensitive and thus is possibly due to metallo-elastase. Fractionation of bronchoalveolar lavage fluid indicated that the elastase-like activity was associated with a high-molecular-mass complex.(ABSTRACT TRUNCATED AT 250 WORDS)
Kelly
F J
FJ
Department of Human Nutrition, University of Southampton, U.K.
Town
G I
GI
Phillips
G J
GJ
Holgate
S T
ST
Roche
W R
WR
Postle
A D
AD
D000818:Animals; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D002452:Cell Count; D004195:Disease Models, Animal; D005865:Gestational Age; D006168:Guinea Pigs; D008168:Lung / Q000187:drug effects / Q000196:embryology* / Q000473:pathology; D008171:Lung Diseases / Q000151:congenital* / Q000473:pathology; D009504:Neutrophils / Q000737:chemistry; D010100:Oxygen / Q000494:pharmacology; D010196:Pancreatic Elastase / Q000032:analysis; D011506:Proteins / Q000032:analysis
D011506:Proteins; D010196:Pancreatic Elastase; D010100:Oxygen