Abstract

BACKGROUND
Intestinal ischemia-reperfusion (I/R) injury is a devastating complication in the perioperative period. Dexmedetomidine is commonly applied in the perioperative period. The authors aimed to determine the effects of different doses of dexmedetomidine (given before or after intestinal ischemia) on intestinal I/R injury and to explore the underlying mechanisms.
METHODS
Intestinal I/R injury was produced in rat by clamping the superior mesenteric artery for 1 h followed by 2 h reperfusion. Intravenous infusion of dexmedetomidine was performed at 2.5, 5, and 10 μg · kg(-1) · h(-1) for 1 h before or after ischemic insult. In addition, yohimbine hydrochloride was administered intravenously to investigate the role of α2 adrenoreceptor in the intestinal protection conferred by dexmedetomidine.
RESULTS
Intestinal I/R increased mortality of rats and caused notable intestinal injury, as evidenced by statistically significant increases in Chiu's scores; serum diamine oxidase and tumor necrosis factor-α concentration, accompanied by increases in the intestinal mucosal malondialdehyde concentration; myeloperoxidase activity; and epithelial cell apoptosis (all P < 0.05 vs. Sham). Except malondialdehyde and myeloperoxidase, all changes were improved by the administration of 5 μg · kg(-1) · h(-1) dexmedetomidine before ischemia (all P < 0.05 vs. Injury) but not after ischemia. Infusion of 2.5 μg · kg(-1) · h(-1) dexmedetomidine before or after ischemia produced no beneficial effects, and infusion of 10 μg · kg(-1) · h(-1) dexmedetomidine led to severe hemodynamic suppression. Yohimbine abolished the intestinal protective effect of the 5 μg · kg(-1) · h(-1) dexmedetomidine infusion before ischemia and was accompanied by the disappearance of its antiapoptotic and antiinflammatory effect.
CONCLUSION
Dexmedetomidine administration before, but not after, ischemia dose-dependently protects against I/R-induced intestinal injury, partly by inhibiting inflammatory response and intestinal mucosal epithelial apoptosis via α2 adrenoreceptor activation.

Links

Publisher Full Text

Authors

Zhang XY, Liu ZM, Wen SH, Li YS, Li Y, Yao X, Huang WQ, Liu KX

Institution

Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.

Source

Anesthesiology 116:5 2012 May pg 1035-46

MeSH

Adrenergic alpha-Agonists
Amine Oxidase (Copper-Containing)
Animals
Apoptosis
Blood Gas Analysis
Caspase 3
Dexmedetomidine
Dose-Response Relationship, Drug
Hemodynamics
Intestinal Mucosa
Intestines
Lactic Acid
Male
Malondialdehyde
Peroxidase
Rats
Rats, Sprague-Dawley
Receptors, Adrenergic, alpha-2
Reperfusion Injury
Survival Analysis
Tumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22417965