{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,21]],"date-time":"2026-03-21T08:05:30Z","timestamp":1774080330623,"version":"3.50.1"},"reference-count":47,"publisher":"Oxford University Press (OUP)","issue":"11","license":[{"start":{"date-parts":[[2008,6,1]],"date-time":"2008-06-01T00:00:00Z","timestamp":1212278400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2008,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Rationale<\/jats:title>\n                    <jats:p>In acute inflammatory lung disease in newborn infants, exogenous surfactant only transiently improves lung function. We hypothesized that the transient nature of this protection is in part explained by elevated acid sphingomyelinase (a-SMase) activity that may inactivate surfactant and promote proinflammatory responses.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>We investigated the intermediate-term effects (&amp;gt;12 h) of a-SMase inhibition in a neonatal piglet model of repeated airway lavage by the intratracheal use of the a-SMase inhibitor imipramine, together with exogenous surfactant as a carrier substance.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>After surfactant washout and induction of pulmonary inflammation, lung function was monitored over 24 hours of mechanical ventilation and followed by ex vivo analyses. In addition, we studied the effect of lipopolysaccharide inhalation in a-SMase\u2013deficient mice at 48 hours.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Measurements and Main Results<\/jats:title>\n                    <jats:p>Surfactant washout increased both pulmonary a-SMase activity and ceramide content; this was attenuated by surfactant and prevented in the surfactant plus imipramine group. Compared with surfactant alone, PaO2, dynamic compliance, and extravascular lung water were improved in the final 12 hours in the surfactant plus imipramine group. At 24 hours, lavage fluid leukocyte counts and IL-8 concentrations decreased, and physical surfactant film properties improved. In the mouse model at 48 hours, a-SMase\u2013deficient mice showed reduced pulmonary ceramide levels and attenuated leukocyte influx into the alveolar space.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>We conclude that stabilization of exogenous surfactant by adding imipramine to create a \u201cfortified surfactant preparation\u201d improves lung function in a clinically relevant piglet model, and that this effect can be attributed to the inhibition of a-SMase as evidenced in the mouse model.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1164\/rccm.200705-752oc","type":"journal-article","created":{"date-parts":[[2008,5,17]],"date-time":"2008-05-17T03:52:56Z","timestamp":1210996376000},"page":"1233-1241","source":"Crossref","is-referenced-by-count":52,"title":["Improved Pulmonary Function by Acid Sphingomyelinase Inhibition in a Newborn Piglet Lavage 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Aachen, Germany; and"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Sch\u00fctze","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Universit\u00e4tsklinikum Schleswig-Holstein, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Dieter","family":"Adam","sequence":"additional","affiliation":[{"name":"Institute of Immunology, Universit\u00e4tsklinikum Schleswig-Holstein, Kiel, Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Burkhard","family":"Lachmann","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology, Erasmus University Medical Center, Rotterdam, The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefan","family":"Uhlig","sequence":"additional","affiliation":[{"name":"Institute of Pharmacology and Toxicology, Rheinisch-Westf\u00e4lische Technische Hochschule, Aachen, Germany; 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