Microglial activation caused by a mechanism independent of TLR4 is involved in the development of morphine tolerance. Further studies are necessary to clarify the cellular mechanisms of morphine-induced microglial activation.
BackgroundErythropoietin (EPO), originally identified as a hematopoietic growth factor produced in the kidney and fetal liver, is also endogenously expressed in the central nervous system (CNS). EPO in the CNS, mainly produced in astrocytes, is induced under hypoxic conditions in a hypoxia-inducible factor (HIF)-dependent manner and plays a dominant role in neuroprotection and neurogenesis. We investigated the effect of general anesthetics on EPO expression in the mouse brain and primary cultured astrocytes.Methodology/Principal FindingsBALB/c mice were exposed to 10% oxygen with isoflurane at various concentrations (0.10–1.0%). Expression of EPO mRNA in the brain was studied, and the effects of sevoflurane, halothane, nitrous oxide, pentobarbital, ketamine, and propofol were investigated. In addition, expression of HIF-2α protein was studied by immunoblotting. Hypoxia-induced EPO mRNA expression in the brain was significantly suppressed by isoflurane in a concentration-dependent manner. A similar effect was confirmed for all other general anesthetics. Hypoxia-inducible expression of HIF-2α protein was also significantly suppressed with isoflurane. In the experiments using primary cultured astrocytes, isoflurane, pentobarbital, and ketamine suppressed hypoxia-inducible expression of HIF-2α protein and EPO mRNA.Conclusions/SignificanceTaken together, our results indicate that general anesthetics suppress activation of HIF-2 and inhibit hypoxia-induced EPO upregulation in the mouse brain through a direct effect on astrocytes.
Postoperative continuous infusion of fentanyl is associated with increased orthostatic intolerance and delayed ambulation in patients after gynecologic laparoscopic surgery.
Postoperative OI was common in patients after VATS and significantly associated with delayed ambulation. Advanced age, female gender, and postoperative opioid use were identified as independent predisposing factors for OI.
Nonintubated video-assisted thoracoscopic surgery (VATS) has been reported to be safe and feasible for patients with various thoracic diseases, including those who have respiratory dysfunction. In nonintubated VATS, it is important to maintain spontaneous respiration and to obtain a satisfactory operating field through adequate collapse of the lung by surgical pneumothorax. Therefore, we need to minimize the patient's physical and psychological discomfort by using regional anesthesia and sedation. If analgesia and sedation are inadequate, conversion to intubated general anesthesia may be required. Dexmedetomidine (DEX) is a highly selective α2-adrenoceptor agonist that provides anxiolysis and cooperative sedation without respiratory depression. It seems to be a suitable sedative for nonintubated VATS, especially in high-risk patients for intubated general anesthesia, but there have been no report about its use combined with epidural anesthesia in nonintubated VATS for adult patients. Here, we report three patients with severe respiratory dysfunction who underwent nonintubated VATS for pneumothorax using epidural anesthesia and DEX. In all three patients, DEX infusion was started after placement of an epidural catheter and was titrated to achieve mild sedation, while maintaining communicability and cooperation. This seems to be a promising strategy for nonintubated VATS in patients with respiratory dysfunction, as well as patients with normal respiratory function.
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