| Budget Amount *help |
¥3,300,000 (Direct Cost: ¥3,300,000)
Fiscal Year 2002: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2001: ¥900,000 (Direct Cost: ¥900,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
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| Research Abstract |
The first purpose of this study was to evaluate pathological changes of DAD with various lung injury parameters, (MMP)-2 and -9 activities, and the secound was to evaluate whether lung abnormalities on high-resolution computed tomography (HRCT) scans in experimental hyperoxic lung injury correlate with the pathologic phases of DAD.
The PaO2/FiO2 ratio decreased and the lung wet-to-dry weight ratio increased after hyperoxic exposure. BALF differential cell analysis showed the number of neutrophils to be significantly elevated after hyperoxic exposure. The histological progression of acute lung injury in this model ranged from the early exudative to the early proliferative phase of DAD. There was significant correlation between the exposure periods and histological changes. MMP-2 and -9 activities in BALF were elevated under prolonged hyperoxic exposure. MMP-2 expression in BALF tended to elevate much earlier than MMP-9. MMP-9 activity in BALF correlated significantly with the PaO2/FiO2 r
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atio, the lung wet-to-dry weight ratio, and the number of neutrophils in BALF, whereas MMP-2 activity did not correlate at all with these factors. In immunohistochemical evaluation, strong MMP-2 expression was observed in alveolar macrophages. In contrast, MMP-9 was expressed in neutrophils, alveolar macrophages, and alveolar lining epithelium. MMP-9 activity correlated more closely with the pathological findings of DAD than did MMP-2 activity. These results suggest that this hyperoxic exposure pig is useful for experimental ALI/ARDS model, and MMP-2 and MMP-9, especially MMP-9, play important roles in the pathogenesis of early phase of DAD.
In the experimental hyperoxic DAD model, HRCT findings correlated well with histologic findings from the exudative phase to the early proliferative phase of DAD (rs=0.86, p<0.001). The appearance of traction bronchiolectasis on CT was the earliest, most reliable sign of the progression from the exudative to the early proliferative phase of DAD. The CT findings corresponding to the early exudative phase of DAD were areas of normal attenuation. Thus, the utility of CT may not cover the onset of lung injury to the early exudative phase of DAD. HRCT findings reflect the pathologic phases of DAD, though the early exudative phase cannot be specifically detected by HRCT. The presence of traction bronchiolectasis or bronchiectasis on a CT scan would have potentially useful implications for treatment strategies and prognosis. Less
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