| Budget Amount *help |
¥3,200,000 (Direct Cost: ¥3,200,000)
Fiscal Year 2005: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2004: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 2003: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
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.
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