Surfactant dysfunction is a primary pathophysiologic component in patients with adult respiratory distress syndrome (ARDS). In this study we tested the efficacy of aerosolized surfactant (Sf ) replacement in a severe lung injury model of endotoxin-induced ARDS. Twenty-one certified healthy pigs were anesthetized, surgically prepared for measurement of hemodynamic and lung function, then randomized into one of four groups: (1) control (n = 5), surgical instrumentation only; (2) lipopolysaccharide (LPS) (n = 6), infused with Escherichia coli LPS (100 microgram/kg) without positive end- expiratory pressure (PEEP) and ventilated with a nonhumidified gas mixture of 50% N2O and 50% O2; (3) LPS + PEEP (n = 4), infused with LPS, placed on PEEP (7.5 cm H2O), and ventilated with a humidified gas mixture; and (4) LPS + PEEP + Sf (n = 6), infused with LPS, placed on PEEP, and ventilated with aerosolized Sf (Infasurf, ONY, Inc.). All animals were studied for 6 h. Arterial PO2 significantly decreased in both the LPS and LPS + PEEP groups (LPS + PEEP = 74 +/- 19 mm Hg; LPS = 74 +/- 19 mm Hg, p < 0.05) while venous admixture (Q S/Q T) increased in these groups (LPS + PEEP = 43.3 +/- 3.9%; LPS = 47.7 +/- 11%, p < 0.05) as compared with the control group. PEEP + Sf reduced the fall in PO2 (142 +/- 20 mm Hg) and rise in Q S/Q T (15.1 +/- 3.6%) caused by LPS. Delayed induction of PEEP (2 h following LPS) did not significantly improve any parameter over the LPS group without PEEP in this ARDS model. LPS without PEEP (3.4 +/- 0.2 cells/6,400 micrometer2) caused a marked increase in the total number of sequestered leukocytes in the pulmonary parenchyma as compared with the control group (1.3 +/- 0.1 cells/6,400 micrometer2). LPS + PEEP + Sf (2.3 +/- 0.2 cells/6,400 micrometer2) significantly decreased while LPS + PEEP significantly increased (4.0 +/- 0.2 cells/6,400 micrometer2) the total number of sequestered leukocytes as compared with the LPS without PEEP group. In summary, aerosolized surfactant replacement decreased leukocyte sequestration and improved oxygenation in our porcine model of endotoxin-induced lung injury.

Lutz, C.; Gatto, L. A.; Picone, A.; Paskanik, A.; Nieman, G.; Langenback, E.; Tice, D.; Geller, E. Author Information

Objective: To test the hypothesis that coronary artery reperfusion performed too late to reduce infarct size improves survival by altering left ventricular remodeling and preventing progressive left ventricular dilation.Background: Several clinical trials have suggested that late coronary artery reperfusion without infarct size reduction is associated with a survival benefit. Although the mechanism is not known, survival benefits could be related to decreased infarct expansion associated with late coronary artery reperfusion. Decreased infarct expansion results in decreased left ventricular volume, and the resulting decreased wall stress could prevent or attenuate progressive left ventricular dilation and improve survival.Methods: Rats (n=84) were randomized to undergo sham operation, permanent left coronary artery ligation, or 2 hours of left coronary artery ligation followed by reperfusion. Ten weeks later, hemodynamic measurements were made before and after volume loading. The rats were killed, the hearts were removed, and passive pressurevolume curves were obtained. The hearts were fixed at a constant pressure and analyzed morphometrically.Results: When examined 10 weeks after experimental myocardial infarction, late reperfusion's effects on left ventricular remodeling resulted in reduced left ventricular volume when compared to hearts with infarcts supplied by a permanently occluded coronary artery (1.9 ± 0.1 ml/kg vs. 2.1 ± 0.2 ml/ kg; p < 0.01). Although there was a trend toward less thinning (0.95 ± 0.13 mm vs. 1.00 ± 0.10 mm; p=NS) and less expansion (2.3 ± 0.4 vs. 2.8 ± 0.9; p=NS) in reperfused hearts compared to hearts with a permanently occluded coronary artery, changes in infarct shape 10 weeks after infarction were not significantly different. Reperfusion's beneficial effects on remodeling of noninfarcted myocardium were associated with improved survival. Mortality was higher in the permanently occluded rats than in the reperfused rats (35% vs. 12%; p < 0.05).Conclusion: Late coronary artery reperfusion has a beneficial effect on remodeling of noninfarcted myocardium that results in reduced left ventricular volume in rat hearts examined 10 weeks after infarction. These beneficial effects on left ventricular remodeling are associated with improved survival.

ARTICLESMeasurement of tracheal and bronchial mucus velocities in man: relation to lung clearanceW. M. Foster, E. Langenback, and E. H. BergofskyW. M. Foster, E. Langenback, and E. H. BergofskyPublished Online:01 Jun 1980https://doi.org/10.1152/jappl.1980.48.6.965MoreSectionsPDF (2 MB)Download PDF ToolsExport citationAdd to favoritesGet permissionsTrack citations ShareShare onFacebookTwitterLinkedInWeChat Previous Back to Top Next Download PDF FiguresReferencesRelatedInformation Cited ByInhaled Therapy in Respiratory Disease: The Complex Interplay of Pulmonary Kinetic ProcessesCanadian Respiratory Journal, Vol. 2018Engineering nanomaterials to overcome the mucosal barrier by modulating surface propertiesAdvanced Drug Delivery Reviews, Vol. 124The role of mucus on drug transport and its potential to affect therapeutic outcomesAdvanced Drug Delivery Reviews, Vol. 124A prolonged cough treatment strategy “prolonged cough and airway secretion”Nihon Shoni Arerugi Gakkaishi. The Japanese Journal of Pediatric Allergy and Clinical Immunology, Vol. 32, No. 2Ciliary Function and the Role of Cilia in ClearanceJournal of Aerosol Medicine, Vol. 19, No. 1Deposition Patterns of Polydisperse Aerosols Within Human LungsJournal of Aerosol Medicine, Vol. 6, No. 4The lung mucosa: A critical environmental battlegroundThe American Journal of Medicine, Vol. 91, No. 4Contemporary approaches in aerosolized drug delivery to the lungJournal of Controlled Release, Vol. 17, No. 2Characterizing Lung Aerosol PenetrationJournal of Aerosol Medicine, Vol. 4, No. 3Series distribution of mucociliary clearance of magnetized iron particles in anesthetized dogsRespiration Physiology, Vol. 79, No. 1Airway mucus membrane: effects of beta-adrenergic and anticholinergic stimulationThe American Journal of Medicine, Vol. 81, No. 5Sedimentational deposition of 5 μm aerosol particles in the small airways of the human lungJournal of Aerosol Science, Vol. 15, No. 6 More from this issue > Volume 48Issue 6June 1980Pages 965-971 Copyright & PermissionsCopyright © 1980 the American Physiological Societyhttps://doi.org/10.1152/jappl.1980.48.6.965PubMed7380708History Published online 1 June 1980 Published in print 1 June 1980 Metrics