| Project/Area Number |
10470316
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| Research Category |
Grant-in-Aid for Scientific Research (B).
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Anesthesiology/Resuscitation studies
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| Research Institution | Kanazawa University |
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Principal Investigator |
KOBAYASHI Tsutomu Kanazawa U., School.Med., Professor, 医学部, 教授 (40019922)
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| Co-Investigator(Kenkyū-buntansha) |
TASHIRO Katsumi Kanazwa U.Hospital, Associate Prof., 医学部・附属病院, 講師 (30242556)
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| Project Period (FY) |
1998 – 2000
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| Project Status |
Completed (Fiscal Year 2000)
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| Budget Amount *help |
¥10,200,000 (Direct Cost: ¥10,200,000)
Fiscal Year 2000: ¥2,600,000 (Direct Cost: ¥2,600,000)
Fiscal Year 1999: ¥2,400,000 (Direct Cost: ¥2,400,000)
Fiscal Year 1998: ¥5,200,000 (Direct Cost: ¥5,200,000)
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| Keywords | ARDS / surfactant / dextran / surfactant protein / surfactant inhibitor / surface activity / palmitoyl radical / polymer / 胎便吸入症候群 / 血清蛋白質 / 酸素化能 / 呼吸機能 / 肺サーファクタント / 急性呼吸急迫症候群 / テキストラン / ポリエチレン・グリコール / 血液ガス / 肺コンプライアンス / 急性呼吸窮迫症候群 / アルプミン / 表面吸着速度 / 表面張力 |
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| Research Abstract |
In ARDS, surfactant inhibitors appear and cause respiratory failure. In studies to develop an inhibitor-resistant surfactant, the following results were obtained.
(I) Effects of polysaccharides (dextran). (1) Addition of dextran (40-70kDa) to a mixture of surfactant and serum (a surfactant inhibitor) reversed the inhibited activity and increased tidal volumes of immature newborn rabbits. (2) In rats with ARDS, inhalation of aerosolized surfactant followed by aerosolized dextran improved the lung functions significantly better than that of aerosolized surfactant alone. (3) Dextran reduced surfactant inhibition by meconium, suggesting the therapeutic effects on meconium aspiration syndrome.
(II) Modulation of surfactant proteins. (1) ARDS rats were treated with reconstituted surfactants consisted of synthetic phospholipids plus various doses of surfactant proteins B and C (SP-B ＆ SP-C). It was demonstrated that >0.7% in SP-B and >1.4% in SP-C were needed for the reconstituted surfactant to bring about the therapeutic effects. (2) Monomeric form of SP-C (mSP-C) which lacks palmitoyl radical in the molecular structure does not improve the physiologic function, but polymeric form of mSP-C shows the physiologic function better than normal SP-C.An application of polymeric form of mSP-C was strongly suggested for development of artificial surfactant to treat ARDS patients.
(III) Additional studies. (1) In immature rabbits, positive end-expiratory pressure reversed serum-inhibited function of lung surfactant. (2) Surfactant replacement reversed respiratory failure caused by inhalation of fabric protector. (3) Propofol reduced inflamatory responses.
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