title: Lodixanol inhibits exogenous surfactant therapy in rats with acute respiratory distress syndrome.
abstract: Optimal alveolar distribution of exogenous surfactant is an important determinant of its beneficial effect. This distribution can be determined by suspending surfactant in a radiological contrast medium before intratracheal instillation, followed by radiological imaging. Iodixanol is reported to be a safe contrast medium that causes no lung injury when instilled intratracheally. In this study, the effects of surfactant suspended in saline were compared with surfactant suspended either in 4:1 saline-iodixanol (64 mg iodine x mL(-1)) or in 1:1 saline-iodixanol (160 mg iodine x mL(-1)), on oxygenation and lung mechanics in a rat model of adult respiratory distress syndrome (ARDS) induced by lung lavage. After the induction of ARDS, surfactant instillation improved oxygenation, total lung volume at inflation with a distending pressure of 35 cmH2O, lung volume at transpulmonary pressure of 5 cmH2O and Gruenwald index. The effects of surfactant suspended in 4:1 saline-iodixanol were similar to those of surfactant alone. However, instillation of surfactant suspended in 1:1 saline-iodixanol resulted in significantly lower values in all measured parameters. Surface tension was the lowest in surfactant suspended in saline alone and addition of iodixanol led to an increase in surface tension in a dose-dependent manner. In conclusion, iodixanol at the higher dose caused an inhibition of the exogenous surfactant effect, characterized as a lack of improvement in oxygen tension in arterial blood, low total lung compliance, volume at 5 cmH2O end-expiration and Gruenwald index. This effect of iodixanol was probably due to its high surface tension, especially if a high concentration was used. Surfactant suspended in a lower concentration of iodixanol seems a better alternative, allowing for radiological imaging of the distribution of surfactant when intratracheally instilled.
authors.affiliation: Dept of Anaesthesiology, University Medical Centre Utrecht, The Netherlands. j.kesecioglu@azu.nl
authors.forename: J
authors.initials: J
authors.lastname: Kesecioglu
authors.forename: M J
authors.initials: MJ
authors.lastname: Schultz
authors.forename: J J
authors.initials: JJ
authors.lastname: Haitsma
authors.forename: G J
authors.initials: GJ
authors.lastname: den Heeten
authors.forename: B
authors.initials: B
authors.lastname: Lachmann
mesh_terms: D000818:Animals; D001784:Blood Gas Analysis; D001992:Bronchoalveolar Lavage Fluid / Q000737:chemistry; D003287:Contrast Media / Q000009:adverse effects*; D004347:Drug Interactions; D008171:Lung Diseases / Q000188:drug therapy*; D023421:Models, Animal; D010100:Oxygen / Q000097:blood; D011506:Proteins / Q000032:analysis; D011663:Pulmonary Surfactants / Q000493:pharmacokinetics* / Q000627:therapeutic use*; D051381:Rats; D012129:Respiratory Function Tests / Q000379:methods; D013500:Surface Tension / Q000187:drug effects; D014283:Triiodobenzoic Acids / Q000009:adverse effects*
chemical_list: D003287:Contrast Media; D011506:Proteins; D011663:Pulmonary Surfactants; D014283:Triiodobenzoic Acids; C044834:iodixanol; D010100:Oxygen