Dexmedetomidine Administration before, but Not after, Ischemia Attenuates Intestinal Injury Induced by Intestinal Ischemia-Reperfusion in Rats
ABSTRACT 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.
- SourceAvailable from: Hong Liu
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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 . It has been reported that peak intraoperative plasma concentrations of norepinephrine and epinephrine occurred after cardiopulmonary bypass (CPB) . This is a critical period with a higher blood catecholamine level that is detrimental to patients . "
ABSTRACT: And Objectives: The aim of this retrospective investigation was to study the relationships among chronic kidney disease, acute kidney injury (AKI), and potential benefits by post-bypass dexmedetomidine use in patients undergoing cardiac surgery. The patient data were reviewed from the institutional Society of Thoracic Surgeons National Adult Cardiac Surgery Database after IRB approval. 1,133 patients were identified and divided into two groups: those who received dexmedetomidine or those who did not during the post-bypass period. The postoperative outcomes include the incidence of AKI, any complication and all cause of mortality. Post-bypass dexmedetomidine use was associated with significantly reduced the incidence of total AKI (26.1% vs. 33.75%; adjusted OR, 0.7033; 95%CI, 0.540 to 0.916; p=0.0089). In addition, post-bypass dexmedetomidine use was more likely to reduce the incidence of AKI in these patients with preoperative normal kidney function (Stage1; 32.8% to 22.8%; p=0.0233) and mild CKD (Stage 2; 32.8% to 24.7; p=0.0003) after cardiac surgery. Post-bypass infusion of dexmedetomidine was associated with significantly reduced incidence of any complication and 30-day mortalities. Post-bypass dexmedetomidine use is associated with a significant reduction in the incidence of AKI, especially mild AKI in patients with preoperative normal renal function and mild CKD undergoing cardiac surgery.PLoS ONE 10/2013; 8(10):e77446. DOI:10.1371/journal.pone.0077446 · 3.23 Impact Factor
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- "d) Alpha2A-adrenoceptors including clonidine could negatively regulate the expression of caspase-3 in the neonatal cerebral cortex; exerting their protective roles against anesthetics; so clonidine could be used both as an anesthetic adjuvant and an antiapoptotic agent; its analog, dexmedetomidine, can implement its protective roles to prevent against the apoptotic effects of some anesthetics like isoflurane; their possible role in liver could be the topic of many future researches (62, 71, 73-76, 134). "
ABSTRACT: The modern practice of anesthesia is highly dependent ona group of anesthetic drugs which many of them are metabolized in the liver. The liver, of course, usually tolerates this burden. However, this is not always an unbroken rule. Anesthetic induced apoptosis has gained great concern during the last years; especially considering the neurologic system. However, we have evidence that there is some concern regarding their effects on the liver cells. Fortunately not all the anesthetics are blamed and even some could be used safely, based on the available evidence. Besides, there are some novel agents, yet under research, which could affect the future of anesthetic agents' fate regarding their hepatic effects.Hepatitis Monthly 08/2013; 13(8):e13162. DOI:10.5812/hepatmon.13162 · 1.80 Impact Factor
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- "Bragg et al. reported that the increase of the DAO level in the intestinal lumen correlates with the duration of mesenteric ischemia (14). Currently, DAO measurement is frequently used in experimental studies as an extra supporting marker of intestinal damage with a specificity of 100%, accuracy of 95%, and sensitivity of 94% (16, 30–32). Tsunooka et al. analyzed the coronary bypass grafting of patients in whom cardiopulmonary bypass was either performed or not performed (33). "
ABSTRACT: Introduction There is no valid and reliable diagnostic test for early diagnosis of acute mesenteric ischemia (AMI). The aim of this study was to measure the plasma levels of diamine oxidase (DAO) and citrulline in AMI to gain insight into its early diagnosis. Material and methods A total of 21 Wistar albino rats were divided into three groups, that is, control group, short-term ischemia group, and prolonged ischemia group. The superior mesenteric artery was occluded for 15 min in the short-term ischemia group and for 12 h in the prolonged ischemia group. Twelve hours later, the experiment was terminated and plasma DAO and citrulline levels were measured. Intestinal tissue was evaluated for the histopathological changes. Results Compared to the control group, the short-term and prolonged ischemia groups showed significant increases in the plasma levels of DAO, whereas the plasma citrulline levels decreased significantly. Prolonged ischemia caused a larger increase in the plasma DAO levels and a larger decrease in the plasma citrulline levels compared to the short-term ischemia (p=0.011 and p=0.021, respectively). Intestinal damage was shown to develop more in the prolonged ischemia group (p=0.001). Conclusion In the early period of AMI, the plasma DAO levels increase while citrulline levels decrease, and the extent of these changes depends on the duration of ischemia.Libyan Journal of Medicine 03/2013; 8:1-6. DOI:10.3402/ljm.v8i0.20596 · 1.33 Impact Factor