OCR Text |
Show Effect of Vitamin A Treatment on Lung Structural Development in During Continuous Drainage of Lung and Amniotic Liquids to Simulate Oligohydramnios Introduction: Alveolar formation in the developing lung is impaired in utero by continuous loss of amniotic liquid (oligohydramnios). In this disease, the lungs remain underdeveloped (hypoplastic). Structurally, the saccules that form the potential gas-exchange spaces do not become partitioned by secondary crests, in preparation for birth and air breathing. In animal models of other lung diseases in which alveolar formation is disrupted, alveolar formation can be promoted by treatment with vitamin A derivatives. Whether vitamin A therapy promotes structural formation of potential air spaces (alveoli) during the evolution of oligohydramnios is unknown. Dr. Albertine and his colleagues developed a large-animal model of this disease to determine whether alterations in pulmonary development that occur after continuous drainage of lung and amniotic liquids can be overcome by daily treatment of the affected animals with vitamin A. Thus, the purpose of my project was to analyze the lungs of those animals and two groups of control animals. Methods: I analyzed the lungs from 8 fetal lambs, 4 each that had lung and amniotic fluid drainage for 2 weeks. One set of 4 animals was treated with vitamin A (~5,000 U/day, iv). We also studied 2 sets of 4 animals each at 115d gestation (control for when drainage was begun) and 130d gestation (control for when the experiments were ended). This gestation period in sheep spans the transition from the saccular to the alveolar stages of lung development. These experiments were approved by the IACUC at the University of Utah. The lungs were preserved in fixative, from which slices were cut and mounted on microscope slides. The tissue sections were counterstained to reveal structural details. I used a microscope and an image analysis system (R&M Biometrics, Inc.) to quantify the extent of structural development of the potential gas exchange spaces of the lung (the future alveoli where oxygen and carbon dioxide are exchanged) and the number of small blood vessels that are located around the developing alveoli. Alveolar formation was assessed by examining the partitions (called secondary crests) that divide the distal air spaces into anatomic alveoli. The results are summarized in the table below (mean standard ± deviation). Drainage + Drainage 115d Control 130d Control Vitamin A Secondary Crest Vv (%) 0.20 ± 0.05* 0.12 ± 0.06 0.06 ± 0.02 0.09 ± 0.01 IAS Face Length (mm) 60 ± 6* 138 ± 23 105 ± 16 65 ± 7 Vessels/1000 Tissue Pts 50.6±9.76* 56.0± 20.7 20.9± 6.5 48.7± 0 Drainage + vitamin A treatment was associated with significantly greater formation of secondary crests, significantly smaller wall length between contiguous secondary crests and more vessels per 1000 tissue points compared to the drainage alone group and the 115d control group (*, P<0.05 by ANOVA). Conclusion: We conclude that vitamin A given to fetal lambs during 2 weeks of continuous drainage of lung and amniotic liquids promoted lung development, as reflected by greater formation of distal air spaces (future alveoli). These observations indicate that lung hypoplasia and inhibition of alveolar formation associated with oligohydramnios can be partially counteracted by exogenous vitamin A. Brent Reyburn Class standing: Senior Major: Exercise and Sports Science E-mail: breyburn@yahoo.com Faculty Sponsor: Kurt H. Albertine, Ph.D., Professor Pediatrics, Medicine, and Neurobiology & Anatomy E-mail: kurt.albertine@hsc.utah.edu |