Project description:The basic mechanisms of action for general anesthesia are not fully understood. We thought differences in the neural activation sites of different types of anesthetics and differences in gene expression changes in those brain regions may lead to differences in the incidence of side effects. We performed gene expression analysis using microarrays in the identified regions that have been related to the mechanisms of anesthetic action and side effects. Gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics.
Project description:Background: Propofol is a short-acting anesthetic, which is often used for induction and maintenance of general anesthesia, sedation for mechanically ventilated adults and procedural sedation. Several side effects of propofol are known and a substantial number of patients suffer from post-operative delirium after propofol application. In this study, we analyzed the effect of propofol on the function and protein expression profile on a proteome-wide scale. Methods: We cultured human brain microvascular endothelial cells in the absence and presence of propofol and analyzed the permeability of the blood-brain barrier (BBB) by fluorescein passage and protein expression on a proteome-wide scale by mass spectrometry. Results: Propofol interfered with the function of the blood-brain barrier. This was not due to de-creased adhesion of propofol-treated human brain microvascular endothelial cells. The proteomic analysis revealed that some key pathways in these cells were disturbed, such as oxygen metabolism, DNA damage recognition and response to stress. Conclusions: Propofol has strong effects on protein expression which could explain several side effects of propofol.
Project description:General anesthetics have different efficacies and side effect incidences based on their mechanism of action. However, detailed comparative studies of anesthetics are incomplete. In this study, target brain regions and gene expression changes in these brain regions were determined for sevoflurane and propofol to understand the mechanisms that cause differences among anesthetics. Rats were anesthetized with sevoflurane or propofol for 1 hr, and brain regions with anesthesia-induced changes in neuronal activity were examined by immunohistochemistry and in situ hybridization for c-Fos. Among the identified target brain regions, gene expression analysis was performed in the habenula, the solitary nucleus and the medial vestibular nucleus from laser microdissected samples. Genes altered by sevoflurane and propofol were different and included genes involved in the incidence of postoperative nausea and vomiting and emergence agitation, such as Egr1 and Gad2. GO enrichment analysis showed that the altered genes tended to be evenly distributed in all functional category. The detailed profiles of target brain regions and induced gene expression changes of sevoflurane and propofol in this study will provide a basis for analyzing the effects of each anesthetic agent and the risk of adverse events.
Project description:The purpose of this study is to determine whether anesthesia maintained with propofol results in better one- and five-year-survival than anesthesia maintained with sevoflurane.
Project description:The goal of this observational study is to compare anesthetic modalities (intravenous propofol anesthesia with sevoflurane gas anesthesia) in patients who underwent colorectal cancer resection surgery regarding the outcome of acute kidney injury.
The main questions it aims to answer are:
* is there a difference in acute kidney injury incidence in the two anesthetic modalities?
* is there a difference in plasma creatinine between the two anesthetic modalities?
* are there any patient characteristics or intraoperative factors that effect the incidence of acute kidney injury in either anesthetic modality?
The study will analyze data from the CAN clinical trial database. (Cancer and Anesthesia: Survival After Radical Surgery - a Comparison Between Propofol or Sevoflurane Anesthesia, NCT01975064)
Project description:Sevoflurane is the most commonly used general anesthetic in pediatric surgery, but it has the potential to be neurotoxic. Previous research found that long-term or multiple sevoflurane exposures could cause cognitive deficits in newborn mice but not adult mice, whereas short-term or single inhalations had little effect on cognitive function at both ages. The mechanisms behind these effects, however, are unclear. In the current study, 6- and 60-day-old C57bl mice in the sevoflurane groups were given 3% sevoflurane plus 60% oxygen for three consecutive days, each lasting 2 hours, while those in the control group only got 60% oxygen. The cortex tissues were harvested on the 8th or 62nd day. The tandem mass tags (TMT)pro-based quantitative proteomics combined with liquid chromatography-tandem mass spectrometry (LC-MS/MS) analysi were applied to analyze the influences of multiple sevoflurane anesthesia on the cerebral cortex in mice with various ages. A total of 6247 proteins were measured using the combined quantitative proteomics methods of TMTpro-labeled and LC-MS/MS, 443 of which were associated to the age-dependent neurotoxic mechanism of repeated sevoflurane anesthesia. Our findings would help to further the mechanistic study of age-dependent anesthetic neurotoxicity and contribute to seek for effective protection in the developing brain under general anesthesia.
Project description:Interventions: Group S:induction 2-3% and maintenance 1.5-2.5% of sevoflurane during operation;Group S+L:induction 2-3% and 1.5-2.5%maintenance of sevoflurane during operation, lipid emulsions 1mg/kg/h during operations;Group P:induction and maintenance of propofol 3.0-4.0ug/ml during operation
Primary outcome(s): asprosin;blood glucose;insulin
Study Design: Parallel
Project description:Interventions: total intravenous anesthesia:Propofol anesthesia;Sevoflurane posttreatment:Sevoflurane anesthesia;Propofol combined with sevoflurane anesthesia:Propofol combined with sevoflurane anesthesia;RIPC and propofol anesthesia:Remote ischemic preconditioning and propofol anesthesia;RIPC and sevoflurane posttreatment:Remote ischemic preconditioning and sevoflurane anesthesia;RIPC and propofol combined with sevoflurane anesthesia:Remote ischemic preconditioning and propofol combined with sevoflurane anesthesia
Primary outcome(s): blood pressure;heart rate;SPO2%;Blood gas analysis;Central venous pressure;H-FABP;cTnI;TNF-a;IL-8
Study Design: Parallel
Project description:General anesthesia is thought to suppress the immune system and negatively affect postoperative infection and the long-term prognosis of cancer. However, the mechanism underlying immunosuppression induced by general anesthetics remains unclear. In this study, we focused on propofol, which is widely used for sedation under general anesthesia and intensive care and examined its effects on the T cell function and T cell-dependent immune responses. We found that propofol suppressed T cell glycolytic metabolism, differentiation into effector T cells, and cytokine production by effector T cells. CD8 + T cells activated and differentiated into effector cells in the presence of propofol in vitro showed reduced antitumor activity. Furthermore, propofol treatment suppressed the increase in the number of antigen-specific CD8 + T cells during Listeria infection. In contrast, the administration of propofol improved inflammatory conditions in mouse models of inflammatory diseases, such as OVA-induced allergic airway inflammation, hapten-induced contact dermatitis, and experimental allergic encephalomyelitis. These results suggest that propofol may reduce tumor and infectious immunity by suppressing the T cell function and T cell-dependent immune responses while improving the pathogenesis and prognosis of chronic inflammatory diseases by suppressing inflammation.