Dose-response comparisons of five lung surfactant factor (LSF) preparations in an animal model of adult respiratory distress syndrome (ARDS).
1. We have examined the effects of five different lung surfactant factor (LSF) preparations in the rat lung lavage model. In this model repetitive lung lavage leads to lung injury with some similarities to adult respiratory distress syndrome with poor gas exchange and protein leakage into the alveolar spaces. These pathological sequelae can be reversed by LSF instillation soon after lavage. 2. The tested LSF preparations were: two bovine: Survanta and Alveofact: two synthetic: Exosurf and a protein-free phospholipid based LSF (PL-LSF) and one Recombinant LSF at doses of 25, 50 and 100 mg kg-1 body weight and an untreated control group. 3. Tracheotomized rats (10-12 per dose) were pressure-controlled ventilated (Siemens Servo Ventilator 900C) with 100% oxygen at a respiratory rate of 30 breaths min-1, inspiration expiration ratio of 1:2, peak inspiratory pressure (PIP) of 28 cmH2O at positive end-expiratory pressure (PEEP) of 8 cmH2O. Two hours after LSF administration, PEEP and in parallel PIP was reduced from 8 to 6 (1st reduction), from 6 to 3 (2nd reduction) and from 3 to 0 cmH2O (3rd reduction). 4. Partial arterial oxygen pressure (PaO2, mmHg) at 5 min and 120 min after LSF administration and during the 2nd PEEP reduction (PaO2(PEEP23/3)) were used for statistical comparison. All LSF preparations caused a dose-dependent increase for the PaO2(120'), whereas during the 2nd PEEP reduction only bovine and recombinant LSF exhibited dose-dependency. Exosurf did not increase PaO2 after administration of the highest dose. At the highest dose Exosurf exerted no further improvement but rather a tendency to relapse. The bovine and the Recombinant LSF are superior to both synthetic LSFpreparations.5. In this animal model and under the described specific ventilatory settings, even between bovine LSFpreparations there are detectable differences that are pronounced when compared to synthetic LSFwithout any surfactant proteins. We conclude that the difference between bovine and synthetic LSFpreparations can be overcome by addition of the surfactant protein C.
Häfner
D
D
Byk Gulden, Department of Respiratory Pharmacology, Konstanz, Germany.
Beume
R
R
Kilian
U
U
Krasznai
G
G
Lachmann
B
B
D000818:Animals; D001688:Biological Products; D001784:Blood Gas Analysis; D002417:Cattle; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004338:Drug Combinations; D005233:Fatty Alcohols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D005240:Feasibility Studies; D008055:Lipids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D008297:Male; D010313:Partial Pressure; D010743:Phospholipids; D010767:Phosphorylcholine; D011092:Polyethylene Glycols / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D011175:Positive-Pressure Respiration; D011650:Pulmonary Alveoli / Q000187:drug effects; D011659:Pulmonary Gas Exchange / Q000187:drug effects*; D011663:Pulmonary Surfactants / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D011669:Pulmonary Wedge Pressure / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011994:Recombinant Proteins / Q000494:pharmacology / Q000627:therapeutic use; D012128:Respiratory Distress Syndrome / Q000188:drug therapy*; D014132:Trachea / Q000187:drug effects
D001688:Biological Products; D004338:Drug Combinations; D005233:Fatty Alcohols; D008055:Lipids; D010743:Phospholipids; D011663:Pulmonary Surfactants; D011994:Recombinant Proteins; C078272:SF-RI 1, bovine surfactant preparation; D010767:Phosphorylcholine; D011092:Polyethylene Glycols; C047049:dipalmitoylphosphatidylcholine, hexadecanol, tyloxapol drug combination; C072197:beractant