Dexmedetomidine Administration before, but Not after, Ischemia Attenuates Intestinal Injury Induced by Intestinal Ischemia-Reperfusion in Rats

Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
Anesthesiology (Impact Factor: 5.88). 03/2012; 116(5):1035-46. DOI: 10.1097/ALN.0b013e3182503964
Source: PubMed


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.
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.
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.
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.

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    • "Previous studies have demonstrated a beneficial effect of this drug in the brain, reducing oxidative stress markers in a rat model of subarachnoid hemorrhage [26]. It also protected against ischemia/reperfusion injury in tissues such as ovarian [27] or cardiac, [28] [29] whereas it did not show antioxidant effects on intestinal mucosa when administrated either before or after ischemia [24]. Our last finding involves BDNF, a growth factor that protects brain cells from ischemic death [30]. "
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    ABSTRACT: Aims: Dexmedetomidine is a selective agonist of α2-adrenergic receptors with clinical anesthetic and analgesic properties that has also shown neuroprotective effects on several models of brain injury. Because perioperative stroke and brain damage are frequent causes of death in critical care units, we aimed to investigate neuroprotective properties of dexmedetomidine using an in vitro model of cerebral ischemia. Main methods: Primary mixed rat brain cortical cultures were subjected to oxygen and glucose deprivation and treated with different doses of dexmedetomidine in order to analyze three conditioning strategies: preconditioning, intraconditioning and postconditioning. Key findings: All dexmedetomidine pre-, intra- and postconditioning treatments showed neuroprotective effects reducing brain cell necrosis, although only preconditioning showed antiapoptotic effects. Dexmedetomidine treatments also reduced IL-6 and TNF-α levels, especially in the preconditioning groups. Oxidative stress was attenuated with all dexmedetomidine preconditioning treatments, but only with the higher dose in the intraconditioning group, and no effects were observed in the postconditioning. All conditioning strategies increased BDNF levels. Significance: Dexmedetomidine-mediated neuroprotective effects in an in vitro model of cerebral ischemia involve the attenuation of inflammation and oxidative stress and the increment of BDNF expression.
    Full-text · Article · Dec 2015 · Life sciences
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    • "A previous study has shown that the administration of Dex after the I/R period may produce no beneficial effect. However, it was proven to be more effective against I/R damage when used preoperatively (Zhang et al., 2012). In our study, we have applied Dex i.p. to the subjects 60 min before from the detorsion. "
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    Full-text · Article · Nov 2015 · Andrologia
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    • "Since cardiac surgery triggers endocrine responses that stimulates the hypothalamus-pituitary-adrenal axis, the sympathetic nervous system, resulted in epinephrine and norepinephrine release and caused an unstable hemodynamics that is detrimental to renal function [5]. It has been reported that peak intraoperative plasma concentrations of norepinephrine and epinephrine occurred after cardiopulmonary bypass (CPB) [6]. This is a critical period with a higher blood catecholamine level that is detrimental to patients [7]. "
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