title: Effects of eritoran tetrasodium, a toll-like receptor 4 antagonist, on intestinal microcirculation in endotoxemic rats.
abstract: Lipopolysaccharide (LPS) or endotoxin can induce Toll-like receptor 4 signaling and cause microcirculatory dysfunction, which can lead to multiple organ dysfunction. The goal of this study was to investigate whether Toll-like receptor 4 antagonist, eritoran tetrasodium, can attenuate microcirculatory dysfunction in endotoxemic rats. Seventy-two male Wistar rats were divided into three groups as follows: control, LPS, and eritoran + LPS. These rats received laparotomy to exteriorize a segment of terminal ileum for microcirculation examination on intestinal mucosa, muscle, and Peyer patch. The rats in the eritoran + LPS group received 10 mg kg⁻¹ eritoran intravenously. The rats in the LPS and eritoran + LPS groups received 15 mg kg⁻¹ LPS intravenously. Microcirculatory blood flow intensity was measured by full-field laser perfusion imager. Total and perfused small-vessel densities, microvascular flow index, and heterogeneity index were investigated by sidestream dark-field video microscope. Our results revealed that eritoran restored the mean arterial pressure. At 240 min, the microcirculatory blood flow intensity was higher in the eritoran + LPS group than in the LPS group as follows: mucosa (1,094 [SD, 398] vs. 543 [SD, 163] perfusion unit [PU]; P < 0.001), muscle (752 [SD, 124] vs. 357 [SD, 208] PU; P < 0.001), and Peyer patch (961 [SD, 162] vs. 480 [SD, 201] PU; P < 0.001). Eritoran also attenuated endotoxin-induced elevation in the serum level of D-dimer. In conclusion, we have established a promising rat protocol to investigate the intestinal microcirculation in endotoxemia. Our data indicate that eritoran can reduce microcirculatory dysfunction in endotoxemic rats.
authors.affiliation: Department of Anesthesiology, National Taiwan University Hospital, Taipei, Taiwan.
authors.forename: Yu-Chang
authors.initials: YC
authors.lastname: Yeh
authors.forename: Wen-Je
authors.initials: WJ
authors.lastname: Ko
authors.forename: Kuang-Cheng
authors.initials: KC
authors.lastname: Chan
authors.forename: Shou-Zen
authors.initials: SZ
authors.lastname: Fan
authors.forename: Jui-Chang
authors.initials: JC
authors.lastname: Tsai
authors.forename: Ya-Jung
authors.initials: YJ
authors.lastname: Cheng
authors.forename: Wei-Zen
authors.initials: WZ
authors.lastname: Sun
mesh_terms: D000818:Animals; D001783:Blood Flow Velocity / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D004187:Disaccharides / Q000494:pharmacology*; D019446:Endotoxemia / Q000097:blood / Q000503:physiopathology*; D005338:Fibrin Fibrinogen Degradation Products / Q000378:metabolism; D007413:Intestinal Mucosa / Q000378:metabolism; D007422:Intestines / Q000098:blood supply*; D008070:Lipopolysaccharides / Q000633:toxicity; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D051381:Rats; D017208:Rats, Wistar; D013403:Sugar Phosphates / Q000494:pharmacology*; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors* / Q000378:metabolism
chemical_list: D004187:Disaccharides; D005338:Fibrin Fibrinogen Degradation Products; D008070:Lipopolysaccharides; D013403:Sugar Phosphates; C495347:Tlr4 protein, rat; D051197:Toll-Like Receptor 4; C036309:fibrin fragment D; C512420:eritoran