| Japanese |
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| Title | イソフルランのHPV抑制作用へのNOあるいはシクロオキシゲナーゼ代謝産物の関与 |
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| Subtitle | 原著 |
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| Authors | 大嶋嘉明, 石部裕一, 岡崎直人, 日高康蔵, 坂本成司, 佐藤暢 |
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| Organization | 鳥取大学医学部麻酔学教室 |
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| Journal | 循環制御 |
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| Volume | 16 |
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| Number | 4 |
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| Page | 538-544 |
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| Year/Month | 1995/ |
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| Article | 原著 |
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| Publisher | 日本循環制御医学会 |
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| Abstract | 「要旨」吸入麻酔薬は低酸素性肺血管収縮(hypoxic pulmonary vasoconstriction：HPV)を抑制するが, その抑制機序は明らかでない. 今回, イソフルランのHPV反応の抑制機序に一酸化窒素(nitric oxide：NO)あるいはシクロオキシゲナーゼ代謝産物が関与するか否か家兎灌流肺を用いて検討した. 自家血加PSS液を定流量で再灌流し, 吸入酸素濃度を21%から5分間3%に切り替えたときの肺動脈圧上昇値をHPV反応の強さの指標とした. 家兎灌流肺を無処置群, NO合成酵素阻害剤であるNG-monomethyl L-arginine(L-NMMA)30μMを灌流液中に投与した群, インドメタシン10mg・kg-1を全身投与後さらに20μMを灌流液中に投与したシクロオキシゲナーゼ阻害群に分け, それぞれイソフルラン非吸入下, 0.5, 1, 2MAC吸入下のHPV反応を観察した. イソフルラン非吸入下のHPV反応をRMAXとし, 各濃度吸入下のHPV反応(%RMAX)とイソフルラン濃度(MAC)間の用量一反応曲線を非線形最小二乗法で求めた. イソフルランは各群とも用量依存性にHPV反応を抑制した. しかし, ED50は無処置群で0.65±0.12MAC, NO合成酵素阻害群で0.70±0.09MAC, シクロオキシゲナーゼ阻害群で0.96±0.11(mean±SE)MACで, 曲線の傾きslopeは無処置群で1.30±0.13, NO合成酵素阻害群で1.35±0.16, シクロオキシゲナーゼ阻害群で1.88±0.17(mean±SE)であった. シクロオキシゲナーゼ阻害群のED50は無処置群のそれに比較してやや大きく(p=0.08)かつ, 同群のslopeは無処置群のそれに比較して有意に大きく, 同群でイソフルランのHPV抑制作用の減弱を認めた. 以上の結果, イソフルランのHPV抑制機序にNOは関与しないが, シクロオキシゲナーゼ代謝産物は少なからず関与すると考えられた. |
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| Practice | 基礎医学・関連科学 |
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| Keywords | HPV, Isoflurane, NO, Indomethacin, Isolated perfused lung |
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| English |
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| Title | Contribution of NO and/or Cyclooxygenase Products to Isoflurane-induced HPV Inhibition |
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| Authors | Yoshiaki Oshima, Yuichi Ishibe, Naoto Okazaki, Kozo Hidaka, Seiji Sakamoto, Toru Sato |
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| Authors(kana) | |
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| Organization | Department of Anesthesiology, Faculty of Medicine, Tottori University |
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| Journal | Circulation Control |
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| Volume | 16 |
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| Number | 4 |
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| Page | 538-544 |
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| Year/Month | 1995/ |
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| Article | Original article |
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| Publisher | Japan Society of Circulation Control |
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| Abstract | The aim of this study is to test a hypothesis that nitric oxide (NO) and/or cyclooxygenase products are involved with inhibition of hypoxic pulmonary vasoconstriction (HPV) by isoflurane. Lungs isolated from eighteen rabbits were perfused in constant-flow recirculation manner with a mixture of the physiological salt solution and the autologous blood. The HPV response was induced by changing the inspired oxygen concentration from 21 % to 3 % for five min and was evaluated by an increase of the pulmonary artery pressure. End-tidal isoflurane concentration of 0.5, 1, and 2 MAC were tested at random order. The HPV response in the presence of isoflurane was expressed as a percentage of the pressor response in the absence of isoflurane, and the dose-response relationships were calculated using the the nonlinear least-squares method. The following three groups were studied：1) without pretreatment (n=6), 2) pretreatment with NO synthase inhibitor；NG-monomethyl-L-arginine (L-NMMA) 30μM in the reservoir (n=6), and 3) pretreatment with indomethacin 10 mg・kg-1 before surgery and additional indomethacin 20μM in the reservoir (n=6). In all three groups isoflurane depressed HPV in a dose-related manner. The halfinhibition values(ED50) of HPV with isoflurane in the group 1, 2 and 3 were 0.65±0.12, 0.70±0.09, 0.96±0.11MAC(mean±SE), respectively. Slopes of dose response curves in the group 1, 2 and 3 were 1.30±0.13, 1.35±0.16, 1.88±0.17 (mean±SE), respectively. There was a statistical difference of slopes between group 1 and 3. Inhibition of HPV by isoflurane was slightly attenuated with indometthacin pretreatment but L-NMMA pretreatment exerted no more effect on the dose-response curve. It is conceivable that isoflurane may inhibit HPV partially through cyclooxygenase pathway. (Circ Cont 16：538〜544, 1995) |
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| Practice | Basic medicine |
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| Keywords | HPV, Isoflurane, NO, Indomethacin, Isolated perfused lung |
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