Polymer-surfactant treatment of meconium-induced acute lung injury.
Substances (for example, serum proteins or meconium) that interfere with the activity of pulmonary surfactant in vitro may also be important in the pathogenesis or progression of acute lung injury. Addition of polymers such as dextran or polyethylene glycol (PEG) to surfactants prevents and reverses surfactant inactivation. The purpose of this study was to find out whether surfactant/polymer mixtures are more effective for treating one form of acute lung injury than is surfactant alone. Acute lung injury in adult rats was created by tracheal instillation of human meconium. Injured animals, which were anesthetized, paralyzed, and ventilated with 100% oxygen and not treated with surfactant mixtures, remained hypoxic and required high ventilator pressures to maintain Pa(CO(2)) in the normal range over the 3 h of the experiment. Uninjured animals maintained normal values for oxygen and compliance of the respiratory system. The greatest improvement in both oxygenation (178%) and compliance (42%) occurred in animals with lung injury that were treated with Survanta and PEG (versus untreated control animals; p < 0.01), whereas little improvement was found after treatment with Survanta alone. Similar results were found when postmortem pulmonary pressure-volume curves and histology were examined. We conclude that adding PEG to Survanta improves gas exchange, pulmonary mechanics, and histologic appearance of the lungs in a rat model of acute lung injury caused by meconium.
Department of Pediatrics and Physiology, and the Cardiovascular Research Institute, University of California-San Francisco, San Francisco, California, USA. klu@sfghpeds.ucsf.edu
K W
KW
Lu
H
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William Taeusch
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Robertson
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J
Goerke
J A
JA
Clements
D000818:Animals; D001688:Biological Products; D003911:Dextrans / Q000008:administration & dosage*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008168:Lung / Q000473:pathology; D008297:Male; D008471:Meconium Aspiration Syndrome / Q000188:drug therapy* / Q000473:pathology; D009929:Organ Size; D011015:Pneumonia, Aspiration / Q000188:drug therapy* / Q000473:pathology; D011092:Polyethylene Glycols / Q000008:administration & dosage*; D011663:Pulmonary Surfactants / Q000008:administration & dosage*; D051381:Rats; D017207:Rats, Sprague-Dawley
D001688:Biological Products; D003911:Dextrans; D011663:Pulmonary Surfactants; D011092:Polyethylene Glycols; C072197:beractant