Modified natural and synthetically reconstituted surfactant therapies for acute lung injury caused by endotoxin in rats.
BACKGROUND
Impairment of surfactant is involved in development of acute respiratory distress syndrome. To develop artificial surfactant substitute for clinical use, we prepared synthetically reconstituted surfactant (SRS) by adding porcine surfactant-associated protein B and C (SP-B and SP-C) to synthetic phospholipids, and compared its effect with that of modified natural surfactant (MNS) in rats with acute lung injury caused by endotoxin.


METHODS
Escherichia coli endotoxin (71+18 mg x kg(-1), mean+/-SD) was injected into the tracheas of 27 anesthetized and mechanically ventilated rats (FI(O2) of 1.0). When the PaO2 had decreased to below 26.7 kPa, the rats were randomly assigned to three groups. The MNS and SRS groups (n=9, each) were given 100 mg x kg(-1) of MNS and SRS through the airway, respectively. The control group (n=9) was given air in the same volume.


RESULTS
The PaO2 of the control group remained below 13.3 kPa until the end of the experiment (6 h after the assignment). The PaO2 of the MNS group increased to 45.3+/-9.5 kPa and that of the SRS group to 45.5+/-3.7 kPa 0.5 h after the assignment (P<0.05 vs. control group). The PaO2 of both groups remained above 40 kPa throughout the experiment.


CONCLUSIONS
In this acute lung injury model, the effects of replacement therapy with surfactant consisting of synthetic phospholipids, SP-B and SP-C, were the same as those observed with MNS. These results warrant development of surfactant substitutes based on natural SP-B and SP-C, and synthetic phospholipids.
Tashiro
K
K
Department of Emergency and Critical Care Medicine, Kanazawa University Hospital, Japan.
Nishizuka
K
K
Matsumoto
Y
Y
Ohta
K
K
Suzuki
Y
Y
Kobayashi
T
T
D015060:1,2-Dipalmitoylphosphatidylcholine / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004731:Endotoxins / Q000009:adverse effects*; D004926:Escherichia coli; D005500:Follow-Up Studies; D008297:Male; D010100:Oxygen / Q000097:blood; D010313:Partial Pressure; D010713:Phosphatidylcholines / Q000627:therapeutic use; D010715:Phosphatidylglycerols / Q000627:therapeutic use; D011175:Positive-Pressure Respiration; D011510:Proteolipids / Q000627:therapeutic use; D011663:Pulmonary Surfactants / Q000138:chemical synthesis / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*
D004731:Endotoxins; D010713:Phosphatidylcholines; D010715:Phosphatidylglycerols; D011510:Proteolipids; D011663:Pulmonary Surfactants; D015060:1,2-Dipalmitoylphosphatidylcholine; C017251:1,2-oleoylphosphatidylcholine; D010100:Oxygen