Background: Meconium displaces surfactant from the alveolar surface and inhibits its function. The development of active synthetic surfactants is complicated, especially to synthesize the hydrophobic surfactant proteins SP-B and SP-C. A synthetic surfactant, CHF5633 containing SP-B and SP-C analogs, has been designed to act similarly to the natural surfactant poractant alfa. Objective: To test the resistance to meconium inactivation of CHF5633 compared to poractant alfa. Secondary outcome measurements were respiratory and inflammatory parameters. Methods: Twenty-six newborn pigs, bodyweight 1.4-2.0 kg were randomized to receive either poractant alfa or CHF5633. After anesthesia, surgery and final stabilization, meconium was instilled endotracheally followed by surfactant. Bronchial lavage fluid was obtained before intervention and every second hour. Respiratory parameters were registered and blood samples drawn before intervention and every hour. Results: Surfactant was inactivated in both groups 6 h after meconium instillation, but CHF5633 was more resistant than poractant alfa in terms of lipid peroxidation. Respiratory parameters were similar in both groups. Inflammatory and hemostatic parameters differed between groups, suggesting that the surfactants may play different roles in the meconium-induced inflammatory process. Due to the differential effects and complex pattern observed, the data do not indicate that one of the surfactants was superior with respect to inflammatory and hemostatic responses. Conclusion: This study indicates that CHF5633 is as efficient as poractant alfa in experimental meconium aspiration syndrome.

1.
Sato A, Ikegami M: SP-B and SP-C containing new synthetic surfactant for treatment of extremely immature lamb lung. PLoS One 2012;7:e39392.
2.
Cleary GM, Wiswell TE: Meconium-stained amniotic fluid and the meconium aspiration syndrome. An update. Pediatr Clin North Am 1998;45:511-529.
3.
Chen CT, Toung TJ, Rogers MC: Effect of intra-alveolar meconium on pulmonary surface tension properties. Crit Care Med 1985;13:233-236.
4.
Clark DA, Nieman GF, Thompson JE, Paskanik AM, Rokhar JE, Bredenberg CE: Surfactant displacement by meconium free fatty acids: an alternative explanation for atelectasis in meconium aspiration syndrome. J Pediatr 1987;110:765-770.
5.
Castellheim A, Lindenskov PH, Pharo A, Fung M, Saugstad OD, Mollnes TE: Meconium is a potent activator of complement in human serum and in piglets. Pediatr Res 2004;55:310-318.
6.
Mollnes TE, Castellheim A, Lindenskov PH, Salvesen B, Saugstad OD: The role of complement in meconium aspiration syndrome. J Perinatol 2008;28(suppl 3):S116-S119.
7.
Salvesen B, Fung M, Saugstad OD, Mollnes TE: Role of complement and CD14 in meconium-induced cytokine formation. Pediatrics 2008;121:e496-e505.
8.
El Shahed, Dargaville P, Ohlsson A, Soll R: Surfactant for meconium aspiration syndrome in full term/near term infants. Cochrane Database Syst Rev 2007;3:CD002054.
9.
Dargaville PA, Mills JF: Surfactant therapy for meconium aspiration syndrome: current status. Drugs 2005;65:2569-2591.
10.
Salvesen B, Mollnes TE, Saugstad OD: Albumin lavage does not improve the outcome of meconium aspiration syndrome. J Matern Fetal Neonatal Med 2008;21:719-725.
11.
Salvesen B, Stenvik J, Rossetti C, Saugstad OD, Espevik T, Mollnes TE: Meconium-induced release of cytokines is mediated by the TRL4/MD-2 complex in a CD14-dependent manner. Mol Immunol 2010;47:1226-1234.
12.
Moeser AJ, Blikslager AT, Swanson C: Determination of minimum alveolar concentration of sevoflurane in juvenile swine. Res Vet Sci 2008;84:283-285.
13.
Hodgson DS: Comparison of isoflurane and sevoflurane for short-term anesthesia in piglets. Vet Anaesth Analg 2007;34:117-124.
14.
Mollnes TE, Lea T, Harboe M: Detection and quantification of the terminal C5b-9 complex of human complement by a sensitive enzyme-linked immunosorbent assay. Scand J Immunol 1984;20:157-166.
15.
Mollnes TE, Lea T, Froland SS, Harboe M: Quantification of the terminal complement complex in human plasma by an enzyme-linked immunosorbent assay based on monoclonal antibodies against a neoantigen of the complex. Scand J Immunol 1985;22:197-202.
16.
Schurch S, Bachofen H, Goerke J, Possmayer F: A captive bubble method reproduces the in situ behavior of lung surfactant monolayers. J Appl Physiol 1989;67:2389-2396.
17.
Schoel WM, Schurch S, Goerke J: The captive bubble method for the evaluation of pulmonary surfactant: surface tension, area, and volume calculations. Biochim Biophys Acta 1994;1200:281-290.
18.
Almlen A, Stichtenoth G, Linderholm B, et al: Surfactant proteins B and C are both necessary for alveolar stability at end expiration in premature rabbits with respiratory distress syndrome. J Appl Physiol 2008;104:1101-1108.
19.
Dargaville PA, South M, McDougall PN: Surfactant and surfactant inhibitors in meconium aspiration syndrome. J Pediatr 2001;138:113-115.
20.
Moses D, Holm BA, Spitale P, Liu MY, Enhorning G: Inhibition of pulmonary surfactant function by meconium. Am J Obstet Gynecol 1991;164:477-481.
21.
Dargaville PA, Copnell B, Mills JF, et al: Randomized controlled trial of lung lavage with dilute surfactant for meconium aspiration syndrome. J Pediatr 2011;158:383-389.
22.
Seehase M, Collins JJ, Kuypers E, et al: New surfactant with SP-B and C analogs gives survival benefit after inactivation in preterm lambs. PLoS One 2012;7:e47631.
23.
Castellheim A, Lindenskov PH, Pharo A, Aamodt G, Saugstad OD, Mollnes TE: Meconium aspiration syndrome induces complement-associated systemic inflammatory response in newborn piglets. Scand J Immunol 2005;61:217-225.
24.
Okazaki K, Kondo M, Kato M, et al: Serum cytokine and chemokine profiles in neonates with meconium aspiration syndrome. Pediatrics 2008;121:e748-e753.
25.
Warren JS: Interleukins and tumor necrosis factor in inflammation. Crit Rev Clin Lab Sci 1990;28:37-59.
26.
Horvath GL, Schrum JE, De Nardo CM, Latz E: Intracellular sensing of microbes and danger signals by the inflammasomes. Immunol Rev 2011;243:119-135.
27.
Levi M, Ten CH: Disseminated intravascular coagulation. N Engl J Med 1999;341:586-592.
28.
Levi M, van der Poll T, Schultz M: New insights into pathways that determine the link between infection and thrombosis. Neth J Med 2012;70:114-120.
29.
Saetre T, Lindgaard AK, Lyberg T: Systemic activation of coagulation and fibrynolysis in a porcine model of serogroup A streptococcal shock. Blood Coagul Fibrinolysis 2000;11:433-438.
30.
Schultz MJ, Determann RM, Royakkers AA, Wolthuis EK, Korevaar JC, Levi MM: Bronchoalveolar activation of coagulation and inhibition of fibrinolysis during ventilator-associated lung injury. Crit Care Res Pract 2012;2012:961784.
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