Mechanism of Dilatory Action of Volatile Anesthetics on Hyperreactive Airway in Chronic Obstructive Pulmonary Disease Model

挥发性麻醉药对慢性阻塞性肺疾病模型高反应性气道的扩张作用机制

• 批准号: 15591648
• 负责人: YAMAKAGE Michiaki
• 金额: $ 2.05万
• 依托单位: Sapporo Medical University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2003
• 资助国家: 日本
• 起止时间: 2003 至 2005
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/en/grant/KAKENHI-PROJECT-15591648/
• 关键词: Smoking; Guinea Pig; Airway Resistance; Asthma; Ovalbamin; オバラミン(ovalamine)

Background : Little is known about the inhibitory effects of volatile anesthetics on various hyperreactive airway models and the different effects of volatile anesthetics on airway tone. Methods : The effects of sevoflurane (0〜2.0 MAC), the most widely used volatile anesthetic, on hyperreactive airways in ovalbumin-sensitized and chronic cigarette-smoking guinea pigs were investigated by measuring 1)total lung resistance (R_L), 2)muscle tension and intracellular concentration of free Ca^<2+> ([Ca^<2+>]_i) using tracheal ring preparations, 3)voltage-dependent Ca^<2+> channel (VDCC) activity of tracheal smooth muscle cells, and 4)cyclic AMP levels in tracheal smooth muscles. Results : Ovalbumin and muscarinic airway hyperreactivity was seen in ovalbumin-sensitized animals (acute asthmatic model). Muscarinic hyperreactivity and enlarged alveolar ducts/alveoli were observed in chronic cigarette-smoke animals [a chronic obstructive pulmonary disease (COPD), emphysema, model]. Although sevoflurane inhibited the acetylcholine-induced increase in R_L in the control and asthmatic models, the COPD model showed resistance to sevoflurane. Similarly, in the COPD model, carbachol-induced muscle contraction and increased [Ca^<2+>]_i showed resistance to sevoflurane. Sevoflurane had a smaller inhibitory effect on VDCC activity in the COPD group than in the other two groups. The sevoflurane-induced increase in cyclic AMP that was seen in the control and acute-asthmatic groups was significantly suppressed in the COPD group, resulting in an increase in [Ca^<2+>]_i. Conclusions : The COPD model showed resistance to the effects of sevoflurane. The in vitro mechanism of this resistance seemed to be, at least in part, due to the remodeled airway in which sevoflurane-induced cyclic AMP production was suppressed.

背景资料：关于吸入麻醉药对各种高反应性气道模型的抑制作用以及吸入麻醉药对气道张力的不同影响，人们知之甚少。研究方法：七氟烷的作用本实验观察了最常用的吸入麻醉剂0~2.0MAC对卵白蛋白致敏豚鼠和慢性吸烟豚鼠气道高反应性的影响，包括：1）肺总阻力（R_L），2）肌张力和细胞内游离Ca ^2+浓度。（3）气管平滑肌细胞的电压依赖性Ca ^<2 +>通道（VDCC）活性;（4）气管平滑肌中的cAMP水平。结果：卵白蛋白致敏动物（急性哮喘模型）可见卵白蛋白和毒蕈碱气道高反应性。在慢性吸烟动物[慢性阻塞性肺病（COPD），肺气肿模型]中观察到毒蕈碱高反应性和肺泡管/肺泡扩大。七氟醚可抑制哮喘和正常对照大鼠的R_L增加，但COPD模型对七氟醚有抵抗作用。类似地，在COPD模型中，卡巴胆碱诱导的肌肉收缩和[Ca ^<2 +>]_i增加显示对七氟醚的抵抗。七氟烷对COPD组VDCC活性的抑制作用小于其他两组。在COPD组中，七氟醚诱导的环磷酸腺苷升高（在对照组和急性哮喘组中观察到）被显著抑制，导致[Ca ^<2 +>]_i升高。结论：COPD模型对七氟醚的作用具有抵抗性。这种阻力的体外机制似乎是，至少部分是由于重塑的气道，其中七氟烷诱导的环磷酸腺苷的生产受到抑制。

项目成果

麻酔薬と気道過敏症

麻醉药和气道高反应性

• 发表时间: 2005
• 期刊: Aneschesia 21 Century 7・2
• 作者: 山蔭 道明;山蔭 道明
• 通讯作者: 山蔭 道明

麻酔薬と気道過敏性

麻醉药和气道高反应性

• 发表时间: 2005
• 期刊: Anesthesia 21 Century 7・2
• 作者: 山蔭 道明;山蔭 道明;山蔭 道明;山蔭 道明
• 通讯作者: 山蔭 道明

Single-channel activity of L-type Ca^<2+> channel reconstituted with the beta_<2C> subunit cloned from the rat heart

用从大鼠心脏克隆的β_<2C>亚基重建的L型Ca^<2>通道的单通道活性

• 发表时间: 2004
• 期刊: Eur J Pharmacol 487(1-3)
• 作者: 山蔭 道明;山蔭 道明;山蔭 道明;山蔭 道明;山蔭 道明;Michiaki Yamakage;Michiaki Yamakage;Michiaki Yamakage;山蔭 道明;Kamada Y
• 通讯作者: Kamada Y

肺気腫患者の麻酔

肺气肿患者的麻醉

• 发表时间: 2003
• 期刊: LiSA 10・3
• 作者: 山蔭 道明;山蔭 道明;山蔭 道明;山蔭 道明;山蔭 道明;Michiaki Yamakage;Michiaki Yamakage;Michiaki Yamakage;山蔭 道明;Kamada Y;Yamakage M;Yamakage M;Hattori J-I;山蔭 道明;Yasuhiro Kamada;Michiaki Yamakage;Jun-Ichi Hattori;山蔭 道明
• 通讯作者: 山蔭 道明

Changes in concentrations of free propofol by modification of the solution

• DOI: 10.1213/01.ane.0000154191.86608.ac
• 发表时间: 2005-08-01
• 期刊: ANESTHESIA AND ANALGESIA
• 影响因子: 5.7
• 作者: Yamakage, M;Iwasaki, S;Namiki, A
• 通讯作者: Namiki, A