Bronchoalveolar Lavage with KL4-Surfactant in Models of Meconium Aspiration Syndrome

Lavage Administration of Dilute Surfactant in a Piglet Model of Meconium Aspiration

“…In prior studies, meconium was simply administered directly into the normal lung of an animal, including piglets, rats, rabbits, and monkeys [6,8,[25][26][27][30][31][32]. Using this technique, both Cochrane et al [10] and 1 Sun et al [9] suggested that the meconium was unevenly distributed in the lung, leaving certain residual lung regions that appeared well expanded and even normal, presumably because they were beyond the reach of the meconium.…”

“…This has been the basis for exogenous surfactant administration in this disorder. Accordingly, animal [6,[25][26][27][30][31][32]38] and human [1,12,17,18,22] studies have addressed the question of exogenous surfactant treatment in MAS. While the results in animal studies were promising, only one randomized trial of bolus exogenous surfactant has been reported in infants with MAS [12].…”

“…In the past 10 years, several investigators [6,11,18,25,27], including our group [2,3] have reported on a new administration technique for surfactant called "lavage administration." Unfortunately, there are significant differences in the administration technique amongst the studies.…”

Surfactant for Pediatric Acute Lung Injury

“…Two important conceptual approaches being followed to develop synthetic exogenous surfactants are: (1) Combining human sequence recombinant proteins or synthetic amphipathic peptides with synthetic biological glycerophospholipids; and (2) combining synthetic amphipathic peptides with novel synthetic lipids designed to have favorable physicochemical properties such as high surface activity and structural resistance to inflammatory phospholipases during lung injury. Surfaxin® (KL4) [87,107,123,[189][190][191][192][193][194][195] and Venticute® (recombinant SPC surfactant) [26,[196][197][198][199][200][201] are two current examples of the first of these approaches (Table 3). However, the 21 amino acid KL4 peptide is only a very rough structural analog to native SP-B, and advances in peptide molecular modeling and synthesis technology support the feasibility of preparing new SP-B peptides with significantly greater sequence and molecular folding specificity, and correspondingly higher activity ( [202][203][204] for review).…”

“…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.…”