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Show Quantitative Morphology of the Lung Following Three Weeks of Continuous Mechanical Ventilation Introduction: Chronic lung disease of early infancy, often called bronchopulmonary dysplasia (BPD), is a major cause of morbidity and mortality in premature infants. The pathology of this condition includes non-uniform patterns of inflation, saccular appearance of the distal air spaces, accumulation of elastic fibers in the walls of the distal air spaces, and lung inflammation and edema. The causes of these pathologic changes have not been identified, but they are associated with the use of prolonged mechanical ventilation and high concentrations of supplemental oxygen. Dr. Albertine and his colleagues developed a large-animal model of this disease to determine whether alterations in pulmonary development occur after prolonged mechanical ventilation of immature lungs in an experimental model designed to achieve normal respiratory gas exchange without excessive oxygen exposure. Continuous mechanical ventilation for three weeks, in the absence of high concentrations of oxygen in arterial blood, resulted in structural abnormalities in the lungs of prematurely delivered lambs. Compared to control term lambs that were matched for gestation age or postnatal age, chronically ventilated preterm lambs had pulmonary histopathology characterized by non-uniform inflation patterns, impaired alveolar formation, abnormal abundance of elastin, increased muscularization of terminal bronchioles, and inflammation and edema. One of the weaknesses of those studies is they did not include control experiments using normal term lambs that were mechanically ventilated for 3 weeks, as was the case for the preterm lambs. Thus, the purpose of my project was to analyze the lungs of the normal term lambs that were ventilated for three weeks. Methods: The lungs of five term lambs that were mechanically ventilated for 3 weeks were preserved in fixative, from which slices were cut and mounted on microscope slides. These experiments were approved by the IACUC at the University of Utah. 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 alveolar formation (where oxygen and carbon dioxide are exchanged), the number of small blood vessels that are located around the alveoli, and the amount of elastin that was present in the tissue that surrounds the alveoli. Alveolar formation was assessed by examining the partitions (called secondary crests) that divide the distal air spaces into anatomic alveoli. The results (mean standard ± deviation) from my analysis showed that secondary crests occupied 0.209 ± 0.086% of the distal lung tissue, there were 5.55 ± 1.90 small blood vessels (average diameter of 68.57 ± 6.82 mm) per 100 tissue points, and the fraction of elastin in the alveolar walls was 0.283 ± 0.030%. None of these results were different from the historical groups of control lambs that were matched for gestation age or postnatal age. Conclusion: We conclude that mechanical ventilation alone of a normal, term lung is not sufficient to cause pulmonary histopathology that is characteristic of chronic lung disease of early infancy. Therefore, the pulmonary histopathology that is seen in preterm lambs (and by inference, preterm infants) with chronic lung disease of early infancy appears to require immaturity of the lung, as occurs when birth is premature. Conrad Stutznegger Class Standing: Junior Major: History E-mail: conradstutznegger@ hotmail.com Faculty Sponsor:Kurt H. Albertine, Ph.D., Professor Pediatrics, Medicine, and Neurobiology & Anatomy E-mail: kurt.albertine@hsc.utah.edu |
