| Ischemic organs under certain conditions to restore blood reperfusion, cellular functions, metabolic disorders and structural damage not only reduce aggravate, but also will further the aggravate. This phenomenon is called ischemia reperfusion injury(IRI). IRI occurred mostly during anesthesia and intensive care practice. When IRI occur in the limb surgery, we called it limb IRI. Limb IRI in skeletal muscle is inevitable in many vascular and musculoskeletal traumasdiseases, free tissue transfers, during time-consuming reconstructive and transplantation surgeries. Application of tourniquet is liberally used for providing bloodless surgical field and control of intraoperative bleeding in extremity surgery. Muscle ischemia occurs in distal area of tourniquet. Ischemia often leads to energy depletion, accumulation of toxic metabolic products, increase in tissue acidity, activation of phospholipase and lysozymes, and cell damage. Reperfusion can then worsen the injury by inducing cellular infiltration and generating reactive oxygen species, which leads to further cell damage. Skeletal muscle IRI often results in the loss of contractile function, disability, limb amputation, and even death. The mechanism of IRI is mainly achieved through the following two ways, one is due to the oxygen radical-induced lipid peroxidation, so that elevated levels of oxidative stress in the body. On the other hand, neutrophil-mediated inflammation of the factors involved in the inflammatory response. Oxidative stress is the body subjected to a variety of harmful stimulation in vivo highly reactive molecules such as reactive oxygen species which induce the oxidation system and antioxidant system imbalance, leading to tissue damage case. Oxygen radicals damage cells mainly through lipid peroxides, lipid peroxide formation malondialdehyde (MDA) induce primary site and distant organs injury. The substance of clear oxygen free radicals is mainly superoxide dismutase(SOD), SOD reduce leading to more severe IRI. During IRI, tumor necrosisfactor-α (TNF-α) is the earliest and most sensitive inflammatory cytokines and interleukin-8(IL-8) play a more direct role in mediating the inflammatory response. How to prevent and handle the limb IRI, reduce the postoperative complications and mortality has been the one of the most common problems of the anesthesiologist and orthopaedic surgeon. In recent years, Ischemic preconditioning as a preventive measure has get more and more attention. Ischemic preconditioning (IPC) is one of the most effective mechanism within the current endogenous protection. But it is a kind of damage process and many problems limit its clinical application value, incluing how to choose the best time to use it and individual differences. So people put forward to pharmacologic preconditioning (PPC) which can reduce organ damage and producing preconditioning effect. PPC is a method of reducing ischemia-reperfusion injury in accordance with IPC mechanism. Dexmedetomidine (DEX) is a highly selective and potent α2-adrenoreceptor agonist, which was approved by the Food and Drug Administration in1999for patients during the first24h of mechanical ventilation in the intensive care unit.. It can inhibit the sympathetic nervous excitability, enhancing the vagus nerve, sedative, hypnotic, anxiolytic, analgesic, maintain hemodynamic stability, reduce the dose of anesthetics and opioids, and so on. DEX is widely used in the ICU and the process of operation. In addition, with in depth of study we found that the DEX can inhabite lipid peroxidation and stess reaction caused by trauma through the central and peripheral mechanism. A number of studies have demonstrated that DEX has a protective effect against IRI in several organs, including heart, brain, and kidney, which is thought to be because of the antioxidant and anti-inflammatory properties of the compound. However, whether DEX influences IRI of skeletal muscle remains unclear. In the present study, we aimed to study the influence of dexmedetomidine in tourniquet IRI in people through compared the serum level of MDA, SOD, TNF-α, IL-8.ObjectiveTo investigate the effects of dexmedetomidine on changes of oxidative stress and inflammatory cytokines caused by tourniquet-induced limb ischemia-reperfusion injury.Material and methods1Patient preparation and groupingEighty ASA Ⅰ-Ⅱ patients of male or female undergoing lower limb operation with tourniquet were divided randomly into dexmedetomidine group (group DEX,n=40)and control group(group C,n=40). The study was approvaled from the Ethics Committee of Nanfang Hospital, Southern Medical University (Guangzhou, China). All patients were fully informed about the trial and provided signed consent preoperatively. In addition, inclusion criteria comprised normal preoperative liver/kidney kinetic energies, demonstrated an ejection fraction of>55%, without signs of acute infection, without diabetes, no infectious diseases such as tuberculosis, hepatitis, syphilis. No contraindications to spinal canal anesthesia, and who had a preoperative history of the immune system, nervous system and mental illnesswere exclude from the study. All of the patient are the han nationality without relationship. There were no statistical differences in age, gender, weight and tourniquet using time (P>0.05).2Anaesthesia MethedPatients recives no premedication and sedation was limited to maximum of10mg intravenous midazolam. No opioids or other analgesics were administered intraoperatively. All patients had the following monitors:electrocardiogram, automated blood pressure cuff every3min, and finger pulse oximeter. Heart rate and blood pressure trends were recorded for duration of the operative procedure. When the heart rate of less than50beats/min and blood pressure of less than85mmHg or20%lower than basal value at any point in time,5mg ephedine or0.25mg atropine can given respectively.Combined spinal-epidural anesthesia was performed in both groups. The epidural space was identified at the L3-4interspace with an18-gauge. A20-gauge epidural catheter was positioned3cm into the epidural space. The spinal space was identified at the L1-L2Interspace with a27-gauge pencil-point and when cerebrospinal fluid was obtained, the0.5%bupivacaine2ml was injected and then make sure the patient was positioned supine. Contorl the sensory block level under T10. Tourniquet put in the1/3upper of thigh with100mmHg pressure and60minute.3Dosage and AdiministrationIn the group DEX, a dexmedetomidine intravenous infusion was started immediately after the femoral vein cannulated at a dose of1μg/kg for10minutes, followed by0.5μg/kg/h until the end of the operation, whereas group C received an equivalent volume of0.9%saline.4Specimen processing and detectionFemoral venous blood samples were obtained at four time points:T1(before tourniquet inflation)、T2(10min after tourniquet release)、T3(30min after tourniquet release)、T4(60min after tourniquet release). The Serum levels of malondialdehyde (MDA), superoxide dismutase (SOD), tumor necrosisfactor-a (TNF-α) and interleukin-8(IL-8) were measured.5Statistical analysisAll data were expressed as the means±standard (x±s).deviation and were analyzed with the Statistics Package for Social Sciences (SPSS, version19.0for windows; SPSS Inc, Chicago, IL, USA). Statistical analysis was performed using an independent-samples t-test, a repeated measures ANOVA, SNK test and χ2test.Values of P<0.05were considered to be statistically significant.Rusult1The vital signs of two groups patients with different time pointsThere were no significant differences between the group C and group DEX with regard to the vital signs of the patients, including NIBP、HR、 SpO2. In addition, there were no significant differences of every cases in each group about NIBP、HR、SpO2.2The serum level of MDA in two groups patients with different time pointsThere were no significant differences in serum MDA level between two groups before tourniquet inflation (P>0.05). The serum MDA levels at T2-T4were higher than those at T1in the two groups after tourniquet release (P<0.05). Serum MDA level in group DEX at T2-T4were significantly lower than those in group C (P<0.05).3The serum level of SOD in two groups patients with different time pointsThere were no significant differences in serum SOD level between two groups before tourniquet inflation (P>0.05). The serum SOD levels at T2-T4were higher than those at T1in the two groups after tourniquet release (P<0.05). Serum SOD level in group DEX at T2-T4were significantly lower than those in group C (P<0.05).4The serum level of TNF-α in two groups patients with different time pointsThere were no significant differences in serum TNF-α level between two groups before tourniquet inflation (P>0.05). The serumTNF-α levels at T2-T4were higher than those at T1in the two groups after tourniquet release (P<0.05). Serum TNF-a level in group DEX at T2-T4were significantly lower than those in group C (P<0.05).5The serum level of IL-8in two groups patients with different time pointsThere were no significant differences in serum IL-8level between two groups before tourniquet inflation (P>0.05). The serum IL-8levels at T2-T4were higher than those at T1in the two groups after tourniquet release (P<0.05). Serum IL-8level in group DEX at T2-T4were significantly lower than those in group C (P<-0.05).ConclusionDexmedetomidine may possess the ability to reduce oxidative stress and inflammatory cytokines levels, which are caused by tourniquet-induced ischemia-reperfusion injury. |
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