Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesentery during sevoflurane anesthesia

Hiroshi Morisaki, Tomihiro Katayama, Yoshifumi Kotake, Masaharu Ito, Takuya Tamatani, Shinji Sakamoto, Yuzuru Ishimura, Junzo Takeda, Makoto Suematsu

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)


Background: 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 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. Methods: Rats, pretreated with or without hemin, were anesthetized with sevoflurane in 100% O2, and lungs were mechanically ventilated. Platelets labeled with carboxyfluorescein diacetate succinimidyl ester and leukocyte behavior in mesenteric venules were visualized during sevoflurane anesthesia at 1,000 frames/s using intravital ultrahigh-speed intensified fluorescence videomicroscopy. To examine the mechanisms for the effects of HO-1 on leukocyte and platelet behavior, these studies were repeated with superfusion of either CO, bilirubin, or N-nitro-L-arginine methyl ester (L-NAME). Results: As reported previously, the elevation of sevoflurane concentration evoked adhesive responses of leukocytes, concurrent with platelet margination and rolling. Pretreatment with hemin, a HO-1 inducer, prevented such sevoflurane-elicited changes in the microvessels. These changes were restored by zinc protoporphyrin IX, a HO inhibitor, and repressed by CO but not by bilirubin. During sevoflurane anesthesia, however, nitric oxide suppression by L-NAME deteriorated microvascular flows irrespective of the presence or absence of the HO-1 induction. Conclusions: These results indicate that endogenous CO via HO-1 induction attenuates sevoflurane-induced microvascular endothelial interactions with leukocytes and platelets, although local nitric oxide levels appear to dominate microvascular flow in situ.

Original languageEnglish
Pages (from-to)192-199
Number of pages8
Issue number1
Publication statusPublished - 2001

ASJC Scopus subject areas

  • Anesthesiology and Pain Medicine


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