Effects of C1 inhibitor and r-SP-C surfactant on oxygenation and histology in rats with lavage-induced acute lung injury.
OBJECTIVE
To assess the effects of C1 inhibitor (INH) administration and r-SP-C surfactant application on oxygenation and lung histology in an acute respiratory distress syndrome model.


METHODS
Randomized, controlled experimental study in an animal research laboratory.


METHODS
36 adult male Sprague-Dawley rats.


METHODS
Animals were subjected to repetitive lung lavage. Four experimental groups and two control groups were studied: groups 1 and 2 served as controls. Animals of groups 3-6 received 200 U/kg body weight C1-INH (group 3), 25 mg/kg r-SP-C surfactant (group 4) or both (group 5) at 60 min postlavage (pl). Animals of group 6 were treated with 200 U/kg C1-INH1 at 10 min pl. Animals of group 1 were killed 60 min (min) pl, animals of groups 2-6 were killed at 210 min pl. Thereafter the lungs were excised for histological examination.


RESULTS
Hyaline membrane formation, intra-alveolar neutrophil (PMN) accumulation and intra-alveolar/perivascular haemorrhage were graded semiquantitatively (0-4). Blood gases were determined 120, 150, 180 and 210 min pl. At 210 min pl pO(2) in group 4 (456+/-74 mmHg) and group 5 (387+/-155 mmHg) was significantly higher than in controls (72+/-29 mmHg) or after C1-INH monotherapy (group 3: 120+/-103, group 6: 63+/-12 mmHg). PMN infiltration after C1-INH monotherapy was significantly less severe than in controls. The combination of r-SP-C surfactant and C1-INH led to significantly lower PMN infiltration than surfactant monotherapy.


CONCLUSIONS
In this lavage-induced acute respiratory distress syndrome model the administration of C1-INH might be followed by a higher clinical efficacy of exogenously supplied recombinant SP-C surfactant.
Vangerow
B
B
Department of Anaesthesia, Hannover Medical School, 30625 Hannover, Germany.
Häfner
D
D
Rueckoldt
H
H
Marx
G
G
Ott
N
N
Leuwer
M
M
Frerking
I
I
Germann
P G
PG
D000818:Animals; D001706:Biopsy; D001784:Blood Gas Analysis; D003174:Complement C1 Inactivator Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D008297:Male; D009504:Neutrophils; D010101:Oxygen Consumption / Q000187:drug effects*; D011510:Proteolipids / Q000494:pharmacology / Q000627:therapeutic use*; D011663:Pulmonary Surfactants / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use*; D012128:Respiratory Distress Syndrome / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism* / Q000473:pathology; D012720:Severity of Illness Index; D013997:Time Factors
D003174:Complement C1 Inactivator Proteins; D011510:Proteolipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins