Roles of carbon monoxide in leukocyte and platelet dynamics in rat mesenteric during sevoflurane anesthesia.
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 Nomega-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.
Morisaki
H
H
Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan. anesmrsk@med.keio.ac.jp
Katayama
T
T
Kotake
Y
Y
Ito
M
M
Tamatani
T
T
Sakamoto
S
S
Ishimura
Y
Y
Takeda
J
J
Suematsu
M
M
D000769:Anesthesia, Inhalation; D018685:Anesthetics, Inhalation / Q000494:pharmacology*; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001792:Blood Platelets / Q000187:drug effects / Q000502:physiology*; D002248:Carbon Monoxide / Q000502:physiology*; D004790:Enzyme Induction / Q000187:drug effects; D006419:Heme Oxygenase (Decyclizing) / Q000096:biosynthesis; D007962:Leukocytes / Q000187:drug effects / Q000502:physiology*; D008297:Male; D008738:Methyl Ethers / Q000494:pharmacology*; D019007:P-Selectin / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017208:Rats, Wistar; D000077149:Sevoflurane; D013152:Splanchnic Circulation / Q000187:drug effects; D014699:Venules / Q000502:physiology
D018685:Anesthetics, Inhalation; D000911:Antibodies, Monoclonal; D008738:Methyl Ethers; D019007:P-Selectin; D011524:Protoporphyrins; C017803:zinc protoporphyrin; D000077149:Sevoflurane; D002248:Carbon Monoxide; D006419:Heme Oxygenase (Decyclizing)