| Budget Amount *help |
¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1991: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1990: ¥900,000 (Direct Cost: ¥900,000)
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| Research Abstract |
Introduction
It is reported that pulmonary intravascular macrophages (PIMs) play an important role in the formation of lung injury in sheep. In this study, we attempted to elucidate the mechanism of lung injury induced by rabbit anti-sheep albunin serum (AAS) in sheep. Nine unansthetized sheep with chronic lung lymph fistulae were used in this study. AAs were prepared by immunizing rabbits with sheep albumin.
Methods
Study-I. Small amounts of AAS (0.5 ml) were injected intraarterially, and changes in the pulmonary arterial pressure were measured in four sheep. In three sheep, we studied the effects of indomethacin on the AAs-induced rises in pulmonary arterial pressure.
Study-II. Pulmonary hemodynamic and lymph dynamic changes in three unanesthetized sheep with lung lymph fistulae were studied after the AAS injections (3 ml). In two sheep, we examined whether pretreatment with neutrophil elastase inhibitor (ONO 548, 3mg/kg, iv) attenuated AAS-induced lung injury or not, because leukocytopenia was found after the AAS injections.
Results
Study-I. AAS injection induced transitory pulmonary hypertension. Pulmonary arterial pressure rose from the base-line value (14.6 Torr) to 27.3 Torr immediately after the injection. However, this rise was completely blocked pretreatment with indomethacin. Fluorescent microscopic examination demonstrated that anti-sheep albumin antibodies were located on the surface of the PIMs.
Study-II. AAS injection produced pulmonary hypertension with increased lung lymph flow and a sustained lymph-to -plasma protein concentration ratio. The number of arterial-blood neutrophils was decreased, but not inhibitor did not attenuate lung injury or pulmonary hypertension.
Conclusion
From these data, we conclude that rabbit anti-sheep albumin serum injection produces lung permeability edema in which pulmonary intravascular macrophages are involved.
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