Vitamin A Supplementation by Endotracheal Application of a Nano-encapsulated Preparation Is Feasible in Ventilated Preterm Lambs

Holger B. Wahl, Matthias C. Hutten, Dominik Monz, Erol Tutdibi, Daan Ophelders, Maria Nikiforou, Thomas Tschernig*, Ludwig Gortner, Donatus Nohr, Hans K. Biesalski, Boris W. Kramer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

Abstract

Background: Vitamin A (VA) is crucial for lung growth and development. In premature infants, inadequate VA levels are associated with an increased risk of bronchopulmonary dysplasia (BPD). Intramuscular VA supplementation has been shown to decrease the incidence of BPD, but is not widely used in the clinical setting due to concerns about feasibility and pain. We studied VA kinetics, distribution, and the induction of early genetic expression of retinoid homeostatic genes in the lung after endotracheal and intravenous application in a preterm lamb model. Methods: Lambs were delivered prematurely after 85% of gestation, intubated, and ventilated for 3 hours. The animals were randomized to receive no VA (control), a bolus of VA intravenously (i.v.), or VA endotracheally directly after administration of surfactant (e.t.). Results: Animals treated with VA endotracheally directly after administration of surfactant showed significant increases of VA in serum and lung compared to controls. Animals treated with a bolus of VA intravenously showed significant increases of VA in serum, lung, and liver; however, peak serum concentrations and mRNA levels of homeostatic genes raised concerns about toxicity in this group. Conclusions: Endotracheal VA supplementation in preterm lambs is feasible and might offer advantages in comparison to i.v. Further studies are warranted to explore biological effects in the context of BPD.
Original languageEnglish
Pages (from-to)323-330
Number of pages8
JournalJournal of Aerosol Medicine and Pulmonary Drug Delivery
Volume31
Issue number6
DOIs
Publication statusPublished - 1 Dec 2018

Keywords

  • aerosol distribution
  • inhaled therapy
  • small airways
  • ventilation
  • BIRTH-WEIGHT INFANTS
  • CHRONIC LUNG-DISEASE
  • BRONCHOPULMONARY DYSPLASIA
  • RESPIRATORY-DISTRESS
  • RETINYL PALMITATE
  • RETINOIDS
  • INHALATION
  • SURFACTANT
  • CHILDREN
  • PLACEBO
  • ACID
  • PLASMA

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