title: Isoflurane post-treatment improves pulmonary vascular permeability via upregulation of heme oxygenase-1.
abstract: Isoflurane (ISO) has been shown to attenuate acute lung injury (ALI). Induction of heme oxygenase-1 (HO-1) and suppression of inducible nitric oxide synthase (iNOS) expression provide cytoprotection in lung and vascular injury. The aim of this study was to investigate the effect of post-treatment with isoflurane on lung vascular permeability and the role of HO-1 in an ALI rat model induced by cecal ligation and puncture (CLP). Male Sprague-Dawley rats were randomly assigned to one of four groups: sham group, sham rats post-treated with vehicle (Sham); CLP group, CLP rats post-treated with vehicle (CLP); ISO group, CLP rats post-treated with isoflurane (ISO); and ZnPP group, CLP rats injected with zinc protoporphyrin IX (ZnPP), a competitive inhibitor of HO-1, 1 hour before the operation, and post-treated with isoflurane (ZnPP). Isoflurane (1.4%) was administered 2 hour after CLP. At 24 hour after CLP, the extent of ALI was evaluated by lung wet/dry ratio, Evans blue dye (EBD) extravasation, lung permeability index (LPI), as well as histological and immunohistochemical examinations. We also determined pulmonary iNOS and HO-1 expression. Compared with the CLP group, the isoflurane post-treatment group showed improved pulmonary microvascular permeability as detected by EBD extravasation, LPI, as well as histological and immunohistochemical examinations. Furthermore, isoflurane decreased iNOS and increased HO-1 expression in lung tissue. Pretreatment with ZnPP prevented the protective effects of isoflurane in rats. These findings indicate that the protective role of isoflurane post-conditioning against CLP-induced lung injury may be associated with its role in upregulating HO-1 in ALI.
authors.affiliation: Department of Anesthesiology, Shanghai Ninth People's Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
authors.forename: Xiang
authors.initials: X
authors.lastname: Dong
authors.forename: Rong
authors.initials: R
authors.lastname: Hu
authors.forename: Yu
authors.initials: Y
authors.lastname: Sun
authors.forename: Qifang
authors.initials: Q
authors.lastname: Li
authors.forename: Hong
authors.initials: H
authors.lastname: Jiang
mesh_terms: D055371:Acute Lung Injury / Q000188:drug therapy / Q000209:etiology / Q000378:metabolism*; D000818:Animals; D002199:Capillary Permeability / Q000187:drug effects*; D004195:Disease Models, Animal; D051547:Heme Oxygenase-1 / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism*; D007530:Isoflurane / Q000494:pharmacology* / Q000627:therapeutic use; D008168:Lung / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism; D008297:Male; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D011524:Protoporphyrins / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D018805:Sepsis / Q000150:complications; D015854:Up-Regulation / Q000187:drug effects*
chemical_list: D011524:Protoporphyrins; C017803:zinc protoporphyrin; D007530:Isoflurane; D052247:Nitric Oxide Synthase Type II; D051547:Heme Oxygenase-1