| Co-Investigator(Kenkyū-buntansha) |
SAKAI Akio SHINSHU UNIV.SCH.OF MED.ASSOCIATE PROFESSOR, 医学部・附属心脈管研究施設, 助教授 (70020758)
FUJIMOTO Keisaku SHINSHU UNIV.SCH.OF MED.ASSISTANT, 医学部・附属病院, 助手 (70242691)
HONDA Takayuki SHINSHU UNIV.SCH.OF MED.ASSISTANT, 医学部・附属病院, 助手 (80238815)
KOBAYASHI Toshio SHINSHU UNIV.SCH.OF MED.ASSISTANT PROFESSOR, 医学部・附属病院, 講師 (80020775)
SEKIGUCHI Morie SHINSHU UNIV.SCH.OF MED.PROFESSOR, 医学部, 教授 (70075232)
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| Research Abstract |
In this project four stuies were performed. First study was to see the effects of specific neutrophil elastase inhibitor, ONO-5046, on lung dysfunction in endotoxin (ETX)-induced acute lung injury in sheep. E.coli ETX, lug/kg, infusion over 30 min into awake sheep resulted in transient pulmonary hypertension, neutropenia and in increased pulmonary permeability during the late phase. Histologically the early neutropenia was associated with the accumulation of neutrophils in the lungs. Continuous infusion of ONO-5046, 10mg/kg/h, 1h before ETX infusion remarkably blocked these dysfunctions. Second, continous infusion of ONO-5046,1 mg/kg/h, attenuated these dysfunctions with dose dependent manner. Third, continuous infusion of ONO-5046, 10mg/kg/h, 1h after the start of ETX infusion attenuated these dysfunctions. Last study was to see the effects of ONO-5046 on lung dysfunction in microair-embolism-induced acute lung injury in awake sheep. Microair, 1.25 ml/h, over 2 h, was infused through elastic tube (ID 0.3 mm) inserted in the main trunk of the pul monary artery resulted in pumlmary hypertension during air infusion and in increased pulmonary permeability. Neutropenia did not occur. Continuous infusion of ONO-5046, 10mg/kg/h, did not attenuated these dysfunctions induced by air embolism. From these study neutrophil and neutrophil elastase plays an important role of endotoxin-induced lung injury in sheep, but does not relate to air-embolism-induced lung injury.
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