Effect of exogenous surfactant instillation on experimental acute lung injury

Abstract

Pulmonary surfactant replacement has previously been shown to be effective in the human neonatal respiratory distress syndrome. The value of surfactant replacement in models of acute lung injury other than quantitative surfactant deficiency states is, however, uncertain. In this study an acute lung injury model using rats with chronic indwelling arterial catheters, injured with N-nitroso-N-methylurethane (NNNMU), has been developed. The NNNMU injury was found to produce hypoxia, increased mortality, an alveolitis, and alterations in the pulmonary surfactant system. Alterations of surfactant obtained by bronchoalveolar lavage included a reduction in the phospholipid-to-protein ratio, reduced surface activity, and alterations in the relative percentages of the individual phospholipids compared with controls. Treatment of the NNNMU-injured rats with instilled exogenous surfactant (Survanta) improved oxygenation; reduced mortality to control values; and returned the surfactant phospholipid-to-protein ratio, surface activity, and, with the exception of phosphatidylglycerol, the relative percentages of individual surfactant phospholipids to control values.

Surfactant for Pediatric Acute Lung Injury

“…Aspiration of acid [82][83][84]or meconium [85][86][87][88] Anti-lung serum infusion [89] Bacterial or endotoxin-induced injury [90][91][92][93][94][95] Bilateral vagotomy [96] Hyperoxic lung injury [97][98][99][100][101] In vivo lung lavage with mechanical ventilation [102][103][104][105][106][107] NNNMU-induced lung injury [108][109][110] Viral pneumonia [111,112] NNNMU is N-nitroso-N-methylurethane. See text for discussion.…”

Synthetic liposomes are protective from bleomycin-induced lung toxicity

“…Since a major component of lung surfactant is phosphatidylcholine, it is possible that liposomes may have been partly protective by reducing lung surface tension and/or by enhancing fluid clearance in response to bleomycin-induced alveolar edema (42). Because surfactant replacement therapy has been successful in the treatment of neonatal respiratory distress syndrome (1,8,14), it has been considered for the treatment of respiratory diseases in which lung surfactant deficiency or dysfunction also exist, such as acute lung injury or ARDS (2,3,11,13,20,26,27,32,38,44) and pulmonary fibrosis or IPF (17,40), but these applications have had minimal success.…”

“…Surfactant protein (SP)-A and -D are also critical components of innate pulmonary defense (24,43). Lung surfactant deficiency and/or dysfunction have been shown to exist in a number of pulmonary diseases such as neonatal respiratory distress syndrome (RDS) (1,8,14,37), acute lung injury from drugs or toxins (2,13,16,17,20,23,30,32,36,40), ARDS (3,10,11,26,27,38,44), and IPF (12,29). Lung surfactant therapy using protein-free natural animal-derived lung surfactant extracts or synthetic surfactants is a mainstay of current therapy for RDS in neonates (1,8,14) but has met with minimal success in the treatment of adult acute lung injury/ ARDS (3,11,26,44).…”

Pharmacotherapy of Acute Lung Injury and Acute Respiratory Distress Syndrome

“…Abnormalities in surfactant in lung lavage from patients with ALI/ARDS are well-documented [122][123][124][125][126][127][128][129], and exogenous surfactant therapy has a strong rationale based on extensive biophysical research showing that raising surfactant concentration can overcome inhibition by endogenous compounds present in injured lungs ( [52,53,[130][131][132] for review). In addition, the ability of exogenous surfactants to improve pulmonary mechanics and function has been established in multiple animal models of ALI/ARDS including acid aspiration [133][134][135], meconium aspiration [136][137][138][139], anti-lung serum [140], bacterial or endotoxin injury [141][142][143][144][145][146], vagotomy [147], hyperoxia [148][149][150][151][152], in vivo lung lavage [153][154][155][156][157][158], N-nitroso-Nmethylurethane (NNNMU) injury [159][160][161], and viral pneumonia [162,…”