A minimum difference of 0. Based on the institutional result for patients who underwent cardiac surgery, the standard deviation of troponin level was 0. A sample size of at least 27 in each group was required to achieve a power 0. Normal distribution of the data was determined by Shapiro-Wilk test.
Demographic and surgical data were analyzed by Mann-Whitney test. Change of cytokines, MDA, cardiac enzymes and hemodynamic variables at different time points were evaluated using repeated measure ANOVA with Tukey post hoc test for normally distributed variables and Friedman test with Duncan post hoc test for nonnormally distributed variables.
Demographic and surgical data were not different between the two groups Table 1. The required amount of inotropics, vasopressors and the number of units of blood products transfused per transfused patients were not statistically different between groups not shown. There were significant differences between both groups just before aortic declamping: Remarkable differences were found between the two groups. This study evaluated the effects of remifentanil and fentanyl anesthesia on pro-inflammatory cytokines, oxidative stress mediator and myocardial damage markers induced by cardiac surgery using CPB.
Our study showed that the levels of cytokines and oxidative stress mediator such as MDA during CPB and after aortic declamping reperfusion were significantly higher than those pre inductions. In addition, inflammatory reaction occurs as a result of neutrophil accumulation in the myocardium. The neutrophils that migrate to the tissue as a result of the inflammatory process initiate the tissue damage by triggering several reactions [ 12 ]. Neutrophils that accumulate in the tissue secrete myeloperoxidase, which produces hydroxychloride HOCl.
HOCl has a direct cytotoxic effect and by inactivating a 1-protease inhibitor, it participates in the production of collagenases and elastases from the neutrophils [ 13 , 14 ]. Cytokines are intracellular signaling molecules and elicit important defense mechanisms. Consequently, oxygen free radicals and various cytokines are produced, thus exacerbating microcirculation and tissue damage [ 15 , 16 ].
Excessive inflammatory cytokine production activates neutrophils and enhances the expression of adhesion molecules to exacerbate microcirculation and tissue damage [ 17 ]. Therefore, it is important to remove excess amounts of cytokines and active oxygen radicals. Although fentanyl has been previously reported to suppress oxygen free radicals and modulate pro inflammatory cytokines [ 18 ], the present study is clinically significant because it is the first to clarify the anticytokine and antioxidant activity of remifentanil in a clinical situation.
The results may be attributed that remifentanil may be potentially useful therapeutic adjuncts more than fentanyl regard to anti-inflammatory response and free radical scavengers and believed to be an ideal anesthetic that can be used safely.
Opioids have been widely used as anesthetic agents for various types of surgery, including cardiac surgery. The primary actions of opioids are analgesia and sedation. In addition to their analgesic and sedative effects, opioids modulate the immune response via opioid receptors expressed directly on the immune cells themselves. Recently, it has been suggested that the kappa opioid receptor system has a modulatory role in various inflammatory diseases.
The finding that opioid receptors are expressed in numerous types of immune cells [ 19 , 20 ] gave the first indication that opioids may have a direct effect on the immune system. Also, both endogenous and exogenous opioids alter antibody response, cell-mediated immunity, phagocytic activity, chemotaxis, and respiratory burst responses of neutrophils and mononuclear phagocytes [ 21 , 22 ].
Opioidinduced cardioprotection and ischemic preconditioning IPC seem to share a common pathway including protein kinase C and mitochondrial adenosine triphosphate—sensitive potassium KATP channels [ 23 - 25 ]. Remifentanil, an ultrashort-acting opioiod, has been shown to trigger both immediate and delayed cardiac preconditioning in the rat heart [ 26 ].
Our study demonstrated that remifentanil has more effective action than fentanyl on the decrease of cytokines and oxidative stress in the cardiac surgery with CPB. The dosages of drugs, fentanyl and remifentanil were used on the basis of clinical cardiac anesthesia [ 27 ]. The elevation of cardiac biomarkers such as CK-MB and cardiac troponin T after cardiac surgery has been shown to be a good predictor of clinical outcomes. Most patients undergoing cardiac procedures have some degree of postprocedural cardiac biomarker elevation, however, only significant elevations greater than the normal range i.
In this study, both remifentanil and fentanyl attenuated the elevation of troponin T and CK-MB after cardiac surgery and the levels of postoperative cardiac enzymes in the remifentanil group were kept significantly lower compared with the fentanyl group. Similarly, Winterhalter et al. There are several limitations to this study. First, it was not possible to investigate control group which did not use opioid because the use of opioid is standard anesthesia in cardiac surgery.
Therefore, only fentanyl and remifentanil groups were compared. Second, clinically, postoperative outcomes such as mortality, length of intensive care unit and postoperative complications were not investigated. This study was not primarily designed to assess these parameters. The intraoperative laboratory examination and hemodynamic data only were measured. It is imaginable that the benefit of laboratory data as the meaning of lower myocardial damage will be translated into better clinical outcome. Therefore, it will be important to investigate clinical possibility.
In conclusion, in addition to its analgesic and sedative effects, remifentanil attenuated inflammatory cytokine IL-6, and IL-8 , oxidative stress mediator MDA and myocardial damage markers Troponin T and CK-MB and appears to be a promising and useful anesthetic agent for cardioprotection during cardiac surgery with CPB. All Published work is licensed under a Creative Commons Attribution 4. Towards a theory regarding the pathogenesis of the systemic inflammatory response system: What we do and do not know about cytokine regulation.
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Central and peripheral anti-inflammatory actions by clonidine and a structurally related imidazoline analog.
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Inhibitory effects of clonidine on the allergen-induced wheal-and-flare reactions in patients with extrinsic asthma. J Allergy Clin Immunol ; Effects of an alpha-2 adrenoceptor agonist on angiotensin converting enzyme inhibitor-induced hypotension and potentiated allergen-evoked inflammatory skin responses. Anti-inflammatory actions of clonidine, guanfacine and B-HT against various inflammagen-induced acute paw oedema in rats.
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