| Budget Amount *help |
¥5,800,000 (Direct Cost: ¥5,800,000)
Fiscal Year 2000: ¥1,500,000 (Direct Cost: ¥1,500,000)
Fiscal Year 1999: ¥2,500,000 (Direct Cost: ¥2,500,000)
Fiscal Year 1998: ¥1,800,000 (Direct Cost: ¥1,800,000)
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| Research Abstract |
Heme oxygenase-1 (HO-1), induced by a variety of stressors, provides endogenous carbon monoxide (CO) and bilirubin, both of which play consequential roles in organs. The current study was aimed to examine whether induction of HO-1 and its by-products modulated endothelial interaction with circulating leukocytes and platelets evoked by sevoflurane anesthesia in vivo. Rats, pretreated with or without hemin, were anesthetized with sevoflurane in 100% O_2 and lungs were mecanically ventilated. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized under sevoflurane anesthesia at 1,000 frames/sec using intravital ultra-highspeed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on leukocyte and platelet behavior, these studies were repeated with supefusion of either CO (10 μM), bilirubin (10 μM) or N^ω-nitro-L-arginine methyl ester (L-NAME : 100μM). As reported previously,
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the elevation of sevoflurane concentration evoked adhesive responses of leukocytes, concurrent with platelet margination and rolling. Pretreatment with hemin, an HO- 1 inducer, prevented such sevoflurane-elicited changes in the microvessels. These changes were restored by zinc protoporphyrin-IX, an HO inhibitor, and repressed by CO, not bilirubin, supplement. With the induction of HO-1, however, the treatment with L-NAME deteriorated microvascular flows per se under sevoflurane anesthesia. These results indicate that endogenous CO via HO-1 induction attenuates sevoflurane-induced interaction between microvascular endothelial cells and circulating leukocytes and platelets, predominantly through the actions of NO pathway and suggest that sevoflurane anesthesia sensitizes microvascular endothelial cells against NO scavengers. Clinical implication of the present study is that patients with peritonitis or trauma undergoing emergency surgery may be modulated by the application of inhalational anesthesia in view of post-operative inflammatory tissue injury and coagulation abnormality. Less
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