Effects of Dexmedetomidine on Intestinal Microcirculation and Intestinal Epithelial Barrier in Endotoxemic Rats.
Dexmedetomidine reduces cytokine production in septic patients and reduces inflammation and mortality in experimental models of endotoxemia and sepsis. This study investigated whether dexmedetomidine attenuates endothelial dysfunction, intestinal microcirculatory dysfunction, and intestinal epithelial barrier disruption in endotoxemic rats.



Ninety-two male Wistar rats were randomly assigned to the following four groups: (1) Sham; (2) lipopolysaccharide, received IV lipopolysaccharide 15 and 10 mg/kg at 0 and 120 min; (3) dexmedetomidine, received IV dexmedetomidine for 240 min; and (4) lipopolysaccharide + dexmedetomidine, received both lipopolysaccharide and dexmedetomidine. Sidestream dark-field videomicroscope, tissue oxygen monitor, and full-field laser perfusion image were used to investigate the microcirculation of the terminal ileum. Serum endocan level was measured. The Ussing chamber permeability assay, lumen-to-blood gadodiamide passage by magnetic resonance imaging, and bacterial translocation were conducted to determine epithelial barrier function. Mucosal apoptotic levels and tight junctional integrity were also examined.



The density of perfused small vessels in mucosa, serosal muscular layer, and Peyer patch in the lipopolysaccharide + dexmedetomidine group was higher than that of the lipopolysaccharide group. Serum endocan level was lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group. Mucosal ratio of cleaved to full-length occludin and spleen bacterial counts were significantly lower in the lipopolysaccharide + dexmedetomidine group than in the lipopolysaccharide group.



The study finding suggests that dexmedetomidine protects against intestinal epithelial barrier disruption in endotoxemic rats by attenuating intestinal microcirculatory dysfunction and reducing mucosal cell death and tight junctional damage. (Anesthesiology 2016; 125:355-67).
From the Department of Anesthesiology, National Taiwan University Hospital (Y.-C.Y., C.-Y.W., Y.-J.C., C.-M.L., Z.-G.W., W.-Z.S.) and the Graduate Institutes of Physiology, College of Medicine (L.C.-H.Y.), National Taiwan University, Taipei, Taiwan, Republic of China; Department of Medical Imaging, Taipei Buddhist Tzu Chi General Hospital, New Taipei, Taiwan, Republic of China (J.-K.H.); and Department of Anesthesiology, Far Eastern Memorial Hospital, New Taipei, Taiwan, Republic of China (W.-S.C.).
Yu-Chang
YC
Yeh
Chun-Yu
CY
Wu
Ya-Jung
YJ
Cheng
Chih-Min
CM
Liu
Jong-Kai
JK
Hsiao
Wing-Sum
WS
Chan
Zong-Gin
ZG
Wu
Linda Chia-Hui
LC
Yu
Wei-Zen
WZ
Sun
D000818:Animals; D018988:Bacterial Translocation / Q000187:drug effects; D020927:Dexmedetomidine / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects; D019446:Endotoxemia / Q000378:metabolism*; D006993:Hypnotics and Sedatives / Q000494:pharmacology*; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects*; D007422:Intestines / Q000098:blood supply* / Q000187:drug effects; D008070:Lipopolysaccharides / Q000633:toxicity; D008279:Magnetic Resonance Imaging; D008297:Male; D008833:Microcirculation / Q000187:drug effects*; D010101:Oxygen Consumption / Q000187:drug effects; D010539:Permeability; D051381:Rats; D017208:Rats, Wistar; D012039:Regional Blood Flow / Q000187:drug effects; D019108:Tight Junctions / Q000187:drug effects
D006993:Hypnotics and Sedatives; D008070:Lipopolysaccharides; D020927:Dexmedetomidine