title: From the Cover: Prolonged Exposure to Volatile Anesthetic Isoflurane Worsens the Outcome of Polymicrobial Abdominal Sepsis.
abstract: Sepsis continues to result in high morbidity and mortality. General anesthesia is often administered to septic patients, but the impacts of general anesthesia on host defense are not well understood. General anesthesia can be given by volatile and intravenous anesthetics. Our previous in vitro study showed that volatile anesthetic isoflurane directly inhibits leukocyte function-associated antigen-1 (LFA-1) and macrophage-1 antigen (Mac-1), critical adhesion molecules on leukocytes. Thus, the role of isoflurane exposure on in vivo LFA-1 and Mac-1 function was examined using polymicrobial abdominal sepsis model in mice. As a comparison, intravenous anesthetic propofol was given to a group of mice. Wild type, LFA-1, Mac-1, and adhesion molecule-1 knockout mice were used. Following the induction of polymicrobial abdominal sepsis by cecal ligation and puncture, groups of mice were exposed to isoflurane for either 2 or 6 h, or to propofol for 6 h, and their outcomes were examined. Bacterial loads in tissues and blood, neutrophil recruitment to the peritoneal cavity and phagocytosis were studied. Six hours of isoflurane exposure worsened the outcome of abdominal sepsis (P < .0001) with higher bacterial loads in tissues, but 2 h of isoflurane or 6 h of propofol exposure did not. Isoflurane impaired neutrophil recruitment to the abdominal cavity by inhibiting LFA-1 function. Isoflurane also impaired bacterial phagocytosis via complement receptors including Mac-1. In conclusion, prolonged isoflurane exposure worsened the outcome of experimental polymicrobial abdominal sepsis and was associated with impaired neutrophil recruitment and bacterial phagocytosis via reduced LFA-1 and Mac-1 function.
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Sophia
authors.initials: S
authors.lastname: Koutsogiannaki
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Matthew M
authors.initials: MM
authors.lastname: Schaefers
authors.affiliation: Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Okuno
authors.affiliation: Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Mai
authors.initials: M
authors.lastname: Ohba
authors.affiliation: Department of Biochemistry, Juntendo University, School of Medicine, Bunkyo-ku, Tokyo 113-8421, Japan.
authors.forename: Takehiko
authors.initials: T
authors.lastname: Yokomizo
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Gregory P
authors.initials: GP
authors.lastname: Priebe
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: James A
authors.initials: JA
authors.lastname: DiNardo
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Soriano G
authors.initials: SG
authors.lastname: Sulpicio
authors.affiliation: Department of Anesthesiology, Perioperative and Pain Medicine, Boston Children's Hospital, Boston, Massachusetts 02115.
authors.forename: Koichi
authors.initials: K
authors.lastname: Yuki
mesh_terms: D018685:Anesthetics, Inhalation / Q000009:adverse effects*; D000818:Animals; D016207:Cytokines / Q000276:immunology; D004195:Disease Models, Animal; D007530:Isoflurane / Q000009:adverse effects*; D016169:Lymphocyte Function-Associated Antigen-1 / Q000235:genetics / Q000276:immunology*; D016177:Macrophage-1 Antigen / Q000235:genetics / Q000276:immunology*; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D020556:Neutrophil Infiltration / Q000187:drug effects / Q000276:immunology; D010529:Peritoneal Cavity / Q000382:microbiology; D010587:Phagocytosis / Q000187:drug effects / Q000276:immunology; D018805:Sepsis / Q000276:immunology* / Q000378:metabolism / Q000382:microbiology; D016019:Survival Analysis; D013997:Time Factors
chemical_list: D018685:Anesthetics, Inhalation; D016207:Cytokines; D016169:Lymphocyte Function-Associated Antigen-1; D016177:Macrophage-1 Antigen; D007530:Isoflurane
keywords: anesthesia; leukocyte function-associated antigen-1; macrophage-1 antigen.; neutrophil; sepsis