Eleven to twenty-two of newborn human infants with respiratory difficulty treated with artificial ventilation and supplemental oxygen therapy develop a severe chronic lung disease called bronchopulmonary dysplasia (BPD). Anecdotal reports of treatment of BPD with glucocorticoid have suggested that such therapy may be beneficial, but its potential toxicity has limited testing in hyman infants. The chronic lung disease which develops in the newborn C57BL mouse, continuously exposed to increased concentrations of supplemental oxygen (100-80 percent) at normal atmospheric pressure is morphologically similar to BPD seen in the newborn human infant. The hypothesis to be tested in this investigation is that administration of a glucocorticoid (dexamethasone) will protect against the effects of pulmonary oxygen toxicity in the newborn mouse.
The specific aims of this research are to: 1. Determine and measure the protective effect of a glucocorticoid (dexamethasone) on pulmonary oxygen toxicity in the newborn C57BL mouse. 2. Determine the pattern of adminstration (i.e., time of initiation of treatment, dose range, and duration of treatment) which maximizes the protective effect and minimizes the side effect. Protection will be determined by measuring survival, body weight gain, lung wet and dry weight, lung volume, pleural fluid, lung DNA, protein, and hydroxyproline, and pulmonary structural alterations, including the fractional volume of the air space, alveolar interstitium and its individual components, alveolar eptihelial cells, and the thickness of the gas-blood barrier. Acute side effects of the drug will be determined by measuring, in addition to the above, thymus and brain weight, brain DNA, and by postmortem autopsy examination, including blood culture when appropriate.
| Ohtsu, N; Ariagno, R L; Sweeney, T E et al. (1989) The effect of dexamethasone on chronic pulmonary oxygen toxicity in infant mice. Pediatr Res 25:353-9 |
