Protective Effect Of Sevoflurane Research Articles

Protective effect of sevoflurane on lung function of elderly chronic obstructive pulmonary disease patients undergoing total hip arthroplasty

Type 2 diabetes mellitus (T2DM), which is distinguished by increased glucose levels in the bloodstream, is a metabolic disease with a rapidly increasing incidence worldwide. Nevertheless, the etiology and characteristics of the mechanism of T2DM remain unclear. Recently, abundant evidence has indicated that the intestinal microbiota is crucially involved in the initiation and progression of T2DM. The gut microbiome, the largest microecosystem, engages in material and energy metabolism in the human body. In this review, we concentrated on the correlation between the gut flora and T2DM. Meanwhile, we summarized the pathogenesis involving the intestinal flora in T2DM, as well as therapeutic approaches aimed at modulating the gut microbiota for the management of T2DM. Through the analysis presented here, we draw attention to further exploration of these research directions.

PREVENTION OF PATHOLOGICAL EFFECT OF ISCHEMIA-REPERFUSION IN LIVER RESECTION BY SEVOFLURANE PRECONDITIONING.

The intermittent Pringle maneuver remains the major technique for controlling hemorrhage during liver surgery. Nevertheless, this procedure involves a risk of triggering a cascade of pathological changes resulting in the ischemia-reperfusion injury (I/R) effect. The pharmacological prevention of this I/R injury represents a promising approach. The aim of the study was to compare the effects of pharmacological preconditioning with sevoflurane and propofol-based intravenous anesthesia on the postoperative function of the liver as the primary end-point. A prospective cohort study includes the analysis of the data of 73 patients who underwent liver surgery. In the study group (n = 41), preconditioning with sevoflurane inhalation was provided 30 minutes prior to liver resection. In the control group (n = 32), sevoflurane preconditioning was not provided. The primary endpoints were blood lactate concentration shortly after the surgery and one day later; alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activities on postoperative Days 1, 3, and 5 as markers of hepatocyte damage. On postoperative Day 1, in patients of the study group, lactate decreased to preoperative levels, while in the control group, lactate content increased as compared to both preoperative levels and the levels immediately after liver resection. A significant difference in AST activity levels between the groups was registered on Day 5, although this difference was not clinically relevant. The decrease in the prothrombin index in the study group on Day 3 was superior to that in the control group. The multiple regression analysis demonstrated a moderate positive association between the number of resected liver segments and the markers of the functional state of the liver in the study group while in the control group, such association was not significant. The protective effect of sevoflurane on the postoperative function of the liver is manifested by the lower level of blood lactate and the stable level of transaminase activity.

Effects of sevoflurane and its metabolite hexafluoroisopropanol on hypoxia/reoxygenation-induced injury and mitochondrial bioenergetics in murine cardiomyocytes.

The volatile anaesthetic sevoflurane protects cardiac tissue from reoxygenation/reperfusion. Mitochondria play an essential role in conditioning. We aimed to investigate how sevoflurane and its primary metabolite hexafluoroisopropanol (HFIP) affect necrosis, apoptosis, and reactive oxygen species formation in cardiomyocytes upon hypoxia/reoxygenation injury. Moreover, we aimed to describe the similarities in the mode of action in a mitochondrial bioenergetics analysis. Murine cardiomyocytes were exposed to hypoxia (0.2% O2 for 6 h), followed by reoxygenation (air with 5% CO2 for 2 h) in the presence or absence sevoflurane 2.2% or HFIP 4 mM. Lactate dehydrogenase (LDH) release (necrosis), caspase activation (apoptosis), reactive oxygen species, mitochondrial membrane potential, and mitochondrial function (Seahorse XF analyser) were measured. Hypoxia/reoxygenation increased cell death by 44% (+31 to+55%, P<0.001). Reoxygenation in the presence of sevoflurane 2.2% or HFIP 4 mM increased LDH release only by+18% (+6 to+30%) and 20% (+7 to+32%), respectively. Apoptosis and reactive oxygen species formation were attenuated by sevoflurane and HFIP. Mitochondrial bioenergetics analysis of the two substances was profoundly different. Sevoflurane did not influence oxygen consumption rate (OCR) or extracellular acidification rate (ECAR), whereas HFIP reduced OCR and increased ECAR, an effect similar to oligomycin, an adenosine triphosphate (ATP) synthase inhibitor. When blocking the metabolism of sevoflurane into HFIP, protective effects of sevoflurane - but not of HFIP - on LDH release and caspase were mitigated. Together, our data suggest that sevoflurane metabolism into HFIP plays an essential role in cardiomyocyte postconditioning after hypoxia/reoxygenation injury.

Sevoflurane anesthesia ameliorates LPS-induced acute lung injury (ALI) by modulating a novel LncRNA LINC00839/miR-223/NLRP3 axis

BackgroundSevoflurane is considered as a lung-protective factor in acute lung injury (ALI), but the underlying molecular mechanism remains largely unknown. The present study identified for the first time that sevoflurane ameliorated lipopolysaccharide (LPS)-induced ALI through regulating a novel long non-coding RNA LINC00839, and uncovered its regulatory mechanism.MethodsLPS-induced ALI models were established in mice or mouse pulmonary microvascular endothelial cells (MPVECs), and they were administered with sevoflurane. Real-Time quantitative PCR, western blot and bioinformatics analysis were performed to screen the aberrantly expressed long non-coding RNA and the downstream molecules in sevoflurane-treated ALI models, and their roles in the protection effect of sevoflurane were verified by functional recovery experiments.ResultsSevoflurane relieved LPS-induced lung injury, cell pyroptosis and inflammation in vitro and in vivo. LINC00839 was significantly suppressed by sevoflurane, and overexpression of LINC00839 abrogated the protective effects of sevoflurane on LPS-treated MPVECs. Mechanismly, LINC00839 positively regulated NOD-like receptor protein 3 (NLRP3) via sequestering miR-223. MiR-223 inhibitor reversed the inhibitory effects of LINC00839 knockdown on NLRP3-mediated pyroptosis in LPS-treated MPVECs. Furthermore, both miR-223 ablation and NLRP3 overexpression abrogated the protective effects of sevoflurane on LPS-treated MPVECs.ConclusionIn general, our work illustrates that sevoflurane regulates the LINC00839/miR-223/NLRP3 axis to ameliorate LPS-induced ALI, which might provide a novel promising candidate for the prevention of ALI.

Sevoflurane attenuates hepatic ischemia reperfusion injury by the miR-122/Nrf2 pathway

BackgroundSevoflurane can protect organs from ischemia-reperfusion (IR) injury, but the mechanism is still unclear. MicroRNA-122 (miR-122) is a liver-specific microRNA (miRNA) and regulates liver function. Therefore, this study aims to elucidate the relationship between the protective effect of sevoflurane and miR-122 in liver IR injury.MethodsWistar rats were divided into the following groups: sham, IR, IR + sevoflurane, IR + miR-122 antagomir, and IR + miR-122 antagomir + sevoflurane. Hematoxylin and eosin (H&E) staining and Suzuki score were used to evaluate the pathological damage of the liver. The levels of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactate dehydrogenase (LDH), tumor necrosis factor (TNF)-α, interleukin (IL)-1β, IL-6, and IL-10 in the serum and the levels of malondialdehyde (MDA), superoxide dismutase (SOD), and nitric oxide (NO) in the liver homogenate supernatant were detected by using the corresponding kit. Terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) and flow cytometry was applied to evaluate the apoptosis of liver tissues. The expression of nuclear factor E2-related factor 2 (Nrf2), miR-122, p53, and HO-1 in liver tissue was evaluated by using immunohistochemistry, qRT-PCR, and western blot as needed.ResultsCompared to the IR group, the sevoflurane post-treatment or miR-122 antagomir groups showed improved liver injury, decreased Suzuki score, inhibited the levels of AST, ALT, LDH, MDA, NO, TNF-α, IL-1β, and IL-6, increased levels of SOD, IL-10, and inhibited hepatocyte apoptosis. Regarding the molecular mechanism, sevoflurane post-treatment fostered the expression of HO-1, promoted the transport of Nrf2 from cytoplasm to the nucleus, and decreased the expression of miR-122 and p53. The combined use of miR-122 antagomir and sevoflurane enhanced the protective effect of miR-122 antagomir in liver injury in IR rats.ConclusionsSevoflurane protected the liver from IR damage by regulating the miR-122/Nrf2/HO-1 pathway.

Diabetes impairs the protective effects of sevoflurane postconditioning in the myocardium subjected to ischemia/ reperfusion injury in rats: important role of Drp1

BackgroundSevoflurane postconditioning (SevP) effectively relieves myocardial ischemia/reperfusion (I/R) injury but performs poorly in the diabetic myocardium. Previous studies have revealed the important role of increased oxidative stress in diabetic tissues. Notably, mitochondrial fission mediated by dynamin-related protein 1 (Drp1) is an upstream pathway of reactive oxygen production. Whether the ineffectiveness of SevP in the diabetic myocardium is related to Drp1-dependent mitochondrial fission remains unknown. This study aimed to explore the important role of Drp1 in the diabetic myocardium and investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP.MethodsIn the first part of the study, adult male Sprague-Dawley rats were divided into 6 groups. Rats in the diabetic groups were fed with high-fat and high-sugar diets for 8 weeks and injected intraperitoneally with streptozotocin (35 mg/kg). Myocardial I/R was induced by 30 min of occlusion of the left anterior descending branch of the coronary artery followed by 120 min of reperfusion. SevP was applied by continuous inhalation of 2.5 % sevoflurane 1 min before reperfusion, which lasted for 10 min. In the second part of the study, we applied mdivi-1 to investigate whether Drp1 inhibition could restore the cardioprotective effect of SevP in the diabetic myocardium. The myocardial infarct size, mitochondrial ultrastructure, apoptosis index, SOD activity, MDA content, and Drp1 expression were detected.ResultsTTC staining and TUNEL results showed that the myocardial infarct size and apoptosis index were increased in the diabetic myocardium. However, SevP significantly alleviated myocardial I/R injury in the normal myocardium but not in the diabetic myocardium. Additionally, we found an elevation in Drp1 expression, accompanied by more severe fission-induced structural damage and oxidative stress in the diabetic myocardium. Interestingly, we discovered that the beneficial effect of SevP was restored by mdivi-1, which significantly suppressed mitochondrial fission and oxidative stress.ConclusionsOur study demonstrates the crucial role of mitochondrial fission dependent on Drp1 in the diabetic myocardium subjected to I/R, and strongly indicates that Drp1 inhibition may restore the cardioprotective effect of SevP in diabetic rats.

Protective effects of sevoflurane in cerebral ischemia reperfusion injury: a narrative review.

Ischemia/reperfusion (I/R) injury is a phenomenon that the reperfusion of ischemic organs or tissues aggravates their damage, which poses a serious health threat and economic burden to the world. I/R gives rise to a series of physiological and pathological world, including inflammatory response, oxidative stress, brain edema, blood-brain barrier destruction, and neuronal death. Therefore, finding effective treatment measures is extremely important to the recovery of I/R patients and the improvement of long-term quality of life. Sevoflurane is an important volatile anesthetic which has been reported to reduce myocardial I/R damage and infarct size. Sevoflurane also has anti-inflammatory and neuroprotective effects. As reported sevoflurane treatment could reduce nerve function injury, cerebral infarction volume and the level of inflammatory factors. At the same time, there is evidence that sevoflurane can reduce neuron apoptosis and antioxidant stress. The protective effect of sevoflurane in brain injury has been proved to be existed in several aspects, so that a comprehensive understanding of its neuroprotective effect is helpful to exploit new treatment paths for I/R, provide clinicians with new clinical treatment decisions, contribute to the effective treatment of I/R patients and the improvement of quality of life after I/R healing.

Sevoflurane ameliorates adriamycin-induced myocardial injury in rats through the PI3K/Akt/GSK-3β pathway.

The aim of this study was to explore the effects of sevoflurane (SEV) pretreatment on Adriamycin (ADR)-induced myocardial injury through the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/glycogen synthase kinase-3β (GSK-3β) pathway. A total of 24 rats weighing 200-250 g were divided into four groups, including: control group (C group), ADR injection group (ADR group), SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group). H9c2 cells were cultured in vitro and were divided into control group (C group), ADR treatment group (ADR group), and SEV pretreatment group (ADR + SEV group) and inhibitor group (ADR + SEV + LY group) as well. Next, the content of aspartate aminotransferase (AST), lactate dehydrogenase (LDH) and creatine kinase (CK) in the serum was detected via Enzyme-Linked Immunosorbent Assay (ELISA). Hematoxylin-eosin (HE) staining assay was performed to determine the severity of myocardial injury. Meanwhile, the apoptosis rate of cells was detected through terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate-biotin nick end labeling (TUNEL) assay. Additionally, Western blotting (WB) was employed to measure the protein expression levels of phosphorylated (p)-GSK-3β, p-PI3K, Akt and p-Akt. Compared with C group, ADR significantly increased the content of AST, LDH and CK in the serum (p<0.01), reduced protein expression levels of p-GSK-3β, p-PI3K and p-Akt (p<0.01), increased apoptosis rate (p<0.01), and induced myocardial injury. SEV pretreatment significantly alleviated the effect of ADR, manifested as significantly lowered content of AST, LDH and CK in the serum (p<0.01), distinctly elevated protein expression levels of p-GSK-3β, p-PI3K and p-Akt (p<0.01), notably reduced apoptosis rate (p<0.01), and relieved myocardial injury. LY294002 remarkably inhibited the protective effect of SEV against myocardial injury (p<0.01) CONCLUSIONS: SEV is able to prominently ameliorate ADR-induced myocardial injury by regulating the phosphorylation level of the PI3K/Akt/GSK-3β signaling pathway.

Protective effect of sevoflurane preconditioning against cerebral injury in patients after cardiopulmonary bypass and its influences on inflammation, stress and leukocyte NF-κB.

Protective effect of sevoflurane preconditioning against cerebral injury in patients after cardiopulmonary bypass and its influences on inflammation, stress and leukocyte NF-κB.

Study on the Protective Effect of Sevoflurane on H2O2-Induced HK-2 Cells

Background: Renal ischemia reperfusion injury (RIRI) is the main cause of acute kidney injury (AKI). The aim of this study was to investigate whether sevoflurane could protect HK-2 cells treated by H2O2 by improving apoptosis and oxidative stress through TLR4/MyD88/NF-κb signaling pathway. Methods: HK-2 cells was treated with H2O2 to construct the oxidative damage model happened in renal ischemia reperfusion injury (RIRI). CCK-8 assay was performed to analyze the viability of HK-2 cells. The reactive oxygen species (ROS), lactate dehydrogenase (LDH), superoxide dismutase (SOD) and malondialdelyde (MDA) testing kits were used for the detection of oxidative stress related factors. TUNEL assay and Western blot were applied to analyze the apoptosis of HK-2 cells. And, proteins of TLR4/MyD88/NF-κb signaling pathway were also detected by western blot. Results: The viability of H2O2-induced HK-2 cells was decreased compared with the control group. The ROS, SOD and MDA levels were increased and LDH level was decreased in H2O2-induced HK-2 cells. The apoptosis of H2O2-induced HK-2 cells was increased. The expression of Bax was decreased and the expression of Bcl-2 and cleaved caspase 3 were increased in the H2O2-induced HK-2 cells. The expression of TLR4/MyD88/NF-κb signaling pathway was increased in the H2O2-induced HK-2 cells. All these changes were reversed by pretreatment with sevoflurane to some extent in HK-2 cells. Conclusion: In conclusion, sevoflurane pretreatment protects HK-2 cells treated by H2O2 by improving apoptosis and oxidative stress through inhibiting the TLR4/MyD88/NF-κb signaling pathway.

Effects of sevoflurane pretreatment on the apoptosis of rat H9c2 cardiomyocytes and the expression of GRP78.

The protective effect of sevoflurane on apoptosis of rat H9c2 cardiomyocytes induced by H2O2 and the effect on the expression of glucose-regulated protein 78 (GRP78) were investigated. H9c2 cells were routinely cultured and divided into the control, model and sevoflurane groups. Cells in the model group were treated with 400 µM H2O2, and cells in the sevoflurane group were pretreated with sevoflurane prior to treatment with 400 µM H2O2. MTT assay was used to assess cell viability. Annexin V-propidium iodide (AV-PI) double staining flow cytometry was used to detect apoptosis. The intracellular free Ca2+ concentration was measured by the fluorescence-based assay using Fluo-3 AM as a calcium ion fluorescence probe. The mRNA expression level of GRP78 and protein expression levels of GRP78, CHOP and caspase-12 were measured using reverse transcription quantitative polymerase chain reaction (RT-qPCR) and western blot analysis, respectively. The assays showed that after sevoflurane pretreatment the H9c2 cell viability was significantly increased, whereas the H2O2-induced apoptosis, intracellular Ca2+ concentration, mRNA expression of GRP78, and the protein expression of GRP78, CHOP and caspase-12 were all reduced. The results show that pretreatment with sevoflurane inhibited H2O2-induced apoptosis in H9c2 cells. The mechanism may be related to inhibition of the stress-related protein GRP78 expression in endoplasmic reticulum, resulting in decreased intracellular Ca2+ concentration and the downregulation of CHOP and caspase-12 expression levels.

Protective effect of sevoflurane on myocardial ischemia-reperfusion injury in rat hearts and its impact on HIF-1α and caspase-3 expression.

This study was designed to investigate possible protective effects of sevoflurane on myocardial ischemia-reperfusion injury (MIRI) and its impact on expression of HIF-1α and caspase-3 in rats, so as to provide new insights for the treatment of MIRI. Forty SD rats were randomly divided into four groups (n=10) including Sham operation (Sham), ischemia-reperfusion (IR), sevoflurane preconditioning group (Sevo-Pre) and sevoflurane post-conditioning (Sevo-Post) groups. Perfusion was performed using ex vivo heart perfusion. The baseline values of cardiac function were recorded in each group at the end of balanced perfusion and after 60 min of reperfusion. Myocardial infarct size (MIS) was calculated at the end of perfusion using TTC staining. Levels of HIF-1α and caspase-3 protein and HIF-1α (western blotting) and Bcl-2 mRNA (RT-qPCR) were detected at the end of reperfusion. Our results showed no significant differences in cardiac function between the groups at the end of the balanced perfusion. After reperfusion for 60 min, however, the cardiac functions of the Sevo-Pre and Sevo-Post groups were significantly better than those in the IR group, and the MIS at the end of reperfusion was significantly decreased. Western blotting and RT-qPCR showed that expression of HIF-1α protein was significantly increased, expression of caspase-3 protein was significantly decreased and expression of HIF-1α and Bcl-2 mRNA were significantly increased in Sevo-Pre and Sevo-Post groups compared with the levels in the IR group at the end of reperfusion. There were no significant differences in experimental results between Sevo-Pre and Sevo-Post groups. Our data support the idea that sevoflurane can improve MIRI in rats by improving cardiac function and reducing MIS. This protective effect seems to be achieved by activation of HIF-1α and inhibition of caspase-3.

Comparison of the myocardial protective effect of sevoflurane versus propofol in patients undergoing heart valve replacement surgery with cardiopulmonary bypass

BackgroundThis study aimed to compare myocardial protective effects of anaesthesia with intravenous infusion of propofol versus inhalation of sevoflurane in patients undergoing heart valve replacement surgery with cardiopulmonary bypass.MethodsSeventy-six patients undergoing valve replacement with cardiopulmonary bypass were randomly assigned to propofol or sevoflurane anesthesia during the surgery, respectively. For assessing myocardial injury, cardiac troponin I (cTnI) and creatine kinase isozyme (CK-MB) were determined before induction (T0), 0.5 h (T1) and 3 h (T2) after aortic unclamping, and 24 h (T3) and 48 h (T4) after surgery. The concentrations of interleukin (IL)-6 and IL-10 as the systemic inflammatory and anti-inflammatory markers were also measured at above time points.ResultsIn the sevoflurane group, the plasma concentrations of cTnI and CK-MB from Tl to T4 and the levels of IL-6 and IL-10 from T1 to T2 were lower than those in the propofol group. Moreover, a higher ratio of automatic heart beat recovery and a shorter length of intensive care unit or hospital stay were found in the sevoflurane group comparing with the propofol group.ConclusionSevoflurane anaesthesia produced more prominent myocardial protection and attenuated inflammatory response than propofol anaesthesia in patients with valve replacement surgery under cardiopulmonary bypass, resulting in shorter ICU and in-hospital stay.Retrospective clinical trial registrationIdentified as ChiCTR-IOR-16009979 at http://www.chictr.org.cn/.

Reducing Caloric Intake Prevents Ischemic Injury and Myocardial Dysfunction and Affects Anesthetic Cardioprotection in Type 2 Diabetic Rats.

Background. Type 2 diabetes mellitus (T2DM) increases the risk of myocardial ischemia, followed by increased perioperative risk of cardiovascular morbidity. We investigated whether reducing caloric intake reduces ischemic injury and myocardial dysfunction and affects the protective effects of the volatile anesthetic sevoflurane in diet-induced T2DM rats. Methods. Rats received a western (WD) or control diet (CD). Caloric intake was reduced by reversing WD-fed rats to CD. Myocardial function was determined with echocardiography. After 8 weeks of diet feeding, myocardial infarction was induced and the effect of sevoflurane was studied on myocardial function and ischemia/reperfusion injury. Results. WD-feeding resulted in a mild T2DM phenotype and myocardial dysfunction. Sevoflurane further impaired systolic function in WD-fed rats. Unexpectedly, WD-feeding reduced infarct size compared to CD-feeding. Sevoflurane reduced infarct size in CD-fed rats; however it enlarged infarct size in WD-fed rats. Caloric reduction restored myocardial dysfunction and the protective effect of sevoflurane against ischemia compared to WD-fed rats, whereas the protective effects of WD-feeding persisted. Conclusion. Caloric reduction restored the T2DM phenotype and myocardial function, while the cardioprotective properties of WD-feeding or sevoflurane persisted. Our data suggest that reducing caloric intake in T2DM might be a possible intervention to reduce perioperative risk of cardiovascular morbidity.

Comparison of the myocardial protective effect of sevoflurane and isoflurane in high-risk cardiac patients undergoing coronary artery bypass grafting surgery: a randomized study

Objective The aim of this study was to assess the effect of sevoflurane and isoflurane in high-risk cardiac patients undergoing coronary artery bypass grafting surgery. Patients and methods This study included 228 patients undergoing coronary artery bypass grafting surgery. This was a randomized study. This study was carried out at cardiac centers. The patients in this study were divided into two groups. In the sevoflurane group, the patients received sevoflurane (end-tidal concentration of 1–4%) as an inhalational agent during the entire procedure (before, during, and after cardiopulmonary bypass). In the isoflurane group, the patients received isoflurane (end-tidal concentration of 0.5–2%) as an inhalational agent during the entire procedure (before, during, and after cardiopulmonary bypass). The monitors measured the heart rate, mean arterial blood pressure, a continuous ECG with an automatic ST-segment analysis (leads II and V), central venous pressure, mean arterial pulmonary pressure, pulmonary capillary wedge pressure, pulmonary and systemic vascular resistances, cardiac index, urine output, troponin I level, creatine kinase-MB level, required pharmacological, and mechanical support. Results The administration of sevoflurane decreased the heart rate, mean arterial blood pressure, cardiac index, mean arterial pulmonary pressure, and pulmonary and systemic vascular resistances compared with the administration of isoflurane (P Conclusion Sevoflurane is more cardioprotective than isoflurane. It decreases the incidence of myocardial infarction and the requirement for pharmacological and mechanical support, and duration of stay in the ICU and hospital.

Sevoflurane mitigates shedding of hyaluronan from the coronary endothelium, also during ischemia/reperfusion: an ex vivo animal study.

Glycosaminoglycan hyaluronan (HA), a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas) on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C) followed by reperfusion (40 minutes), half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g%) was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the colloid hydroxyethyl starch was significantly decreased by sevoflurane vs the control. We conclude that application of sevoflurane preserves the coronary endothelial glycocalyx, especially HA, sustaining the vascular barrier against ischemic damage. This may explain beneficial effects associated with clinical use of volatile anesthetics against ischemia/reperfusion injury.

The effect of sevoflurane versus propofol anesthesia on troponin I after congenital heart surgery, a randomized clinical trial.

Background:The ischemic preconditioning phenomenon can save myocardium against move severe ischemic damages and reduce infarction size and furthermore a heart rhythm disturbance. In this study we examine relationship between troponin I (as a structural myocardial protein) level and anesthetic agents in the children.Materials and Methods:In this study 84 children under 12 years age before cardiac surgery were divided randomly into two groups of 42 each. For anesthetic maintenance sevoflurane with dose of 0.5-1 MAC was used in Group 1 and 100-150 mg/kg/min of intravenous propofol in Group 2 for maintenance of anesthesia. Troponin I level was assessed 2 before and 1 hour after anesthetic induction. Outcome measures included the serum cardiac troponin I level in children before and after surgery in two study groups.Results:There was no significant difference between two groups in indices and both groups were homogenous in this point of view. The troponin I level after surgery was significantly increased in two groups. In the sevoflurane group it was 0.04 ± 0.12 to 0.05 ± 0.09 ng/ml (P value = 0.003) and the propofol group was 0.12 ± 0.26 to 0.19 ± 0.38 ng/ml (P value = 0.001).Conclusions:In this study two Anesthetic regimens were compared to assess the mean troponin I level before and after pediatric closed heart surgery, and it was shown that mean troponin level before and after surgery in the sevoflurane group was less than the propofol group. But this result was not statistically significant. These results indicate that although more protective effects of sevoflurane on myocardial injuries during pediatric cardiac surgery is predominant but this effect has no significant difference in the propofol group.

Sevoflurane prevents liver inflammatory response induced by lung ischemia-reperfusion.

Transplants cause ischemia-reperfusion (IR) injury that can affect distant organs. Liver is particularly sensitive to IR injury. The present randomized experimental study was designed to investigate a possible protective effect of sevoflurane against liver inflammatory response to lung IR in a lung upper lobe left autotransplant model. Two groups (sevoflurane and control) of eight swines each were submitted to upper lobe left lung autotransplant. Hypnotic maintenance was performed with sevoflurane 3% or propofol 8 to 10 mg/kg per hr until pneumonectomy was done; then propofol was used for all animals. Blood and liver samples were taken in four different moments: prepneumonectomy, prereperfusion, 10 min postreperfusion and 30 min postreperfusion to measure levels of interleukin (IL)-1β, IL-10, tumor necrosis factor (TNF)-α, monocyte chemotactic protein (MCP)-1, nuclear factor (NF)-κB, C-reactive protein, ferritin and caspase 3. Non-parametric test was used to find statistical meaning. Lung IR markedly increased the expression of TNF-α, IL-1β, MCP-1, NF-κB and caspase activity in control livers compared with basal levels, whereas liver IL-10 expression decreased 10 and 30 min post-reperfusion. Sevoflurane significantly decreased TNF-α, IL-1β, MCP-1, NF-κB liver expression and caspase 3 activity. Sevoflurane also reverted the lung IR-induced decrease in IL-10 expression. The present results indicate that lung IR caused hepatic injury. Sevoflurane attenuated liver injury in a model of upper lobe left lung autotransplant in pigs.

Neuroprotective Effects of Sevoflurane against Electromagnetic Pulse-Induced Brain Injury through Inhibition of Neuronal Oxidative Stress and Apoptosis

Electromagnetic pulse (EMP) causes central nervous system damage and neurobehavioral disorders, and sevoflurane protects the brain from ischemic injury. We investigated the effects of sevoflurane on EMP-induced brain injury. Rats were exposed to EMP and immediately treated with sevoflurane. The protective effects of sevoflurane were assessed by Nissl staining, Fluoro-Jade C staining and electron microscopy. The neurobehavioral effects were assessed using the open-field test and the Morris water maze. Finally, primary cerebral cortical neurons were exposed to EMP and incubated with different concentration of sevoflurane. The cellular viability, lactate dehydrogenase (LDH) release, superoxide dismutase (SOD) activity and malondialdehyde (MDA) level were assayed. TUNEL staining was performed, and the expression of apoptotic markers was determined. The cerebral cortexes of EMP-exposed rats presented neuronal abnormalities. Sevoflurane alleviated these effects, as well as the learning and memory deficits caused by EMP exposure. In vitro, cell viability was reduced and LDH release was increased after EMP exposure; treatment with sevoflurane ameliorated these effects. Additionally, sevoflurane increased SOD activity, decreased MDA levels and alleviated neuronal apoptosis by regulating the expression of cleaved caspase-3, Bax and Bcl-2. These findings demonstrate that Sevoflurane conferred neuroprotective effects against EMP radiation-induced brain damage by inhibiting neuronal oxidative stress and apoptosis.

Decreased Brain KATP Channel Contributes to Exacerbating Ischemic Brain Injury and the Failure of Neuroprotection by Sevoflurane Post-Conditioning in Diabetic Rats

Diabetes leads to exacerbating brain injury after ischemic stroke, but the underlying mechanisms and whether therapeutic intervention with anesthetic post-conditioning can induce neuroprotection in this population are not known. We tested the hypothesis that alteration of brain mitochondrial (mito) KATP channels might cause exacerbating brain injury after ischemic stroke and attenuate anesthetic post-conditioning induced neuroprotection in diabetes. We also examined whether hyperglycemic correction with insulin would restore anesthetic post-conditioning in diabetes. Non-diabetic rats and diabetic rats treated with or without insulin were subjected to focal cerebral ischemia for 2 h followed by 24 h of reperfusion. Post-conditioning was performed by exposure to sevoflurane for 15 min, immediately at the onset of reperfusion. The role of the mitoKATP channel was assessed by administration of a selective blocker 5-hydroxydecanoate (5-HD) before sevoflurane post-conditioning or by diazoxide (DZX), a mitoKATP channel opener, given in place of sevoflurane. Compared with non-diabetic rats, diabetic rats had larger infarct volume and worse neurological outcome at 24 h after ischemia. Sevoflurane or DZX reduced the infarct volume and improved neurological outcome in non-diabetic rats but not in diabetic rats, and the protective effects of sevoflurane in non-diabetic rats were inhibited by pretreatment with 5-HD. Molecular studies revealed that expression of Kir6.2, an important mitoKATP channel component, was decreased in the brain of diabetic rats as compared to non-diabetic rats. In contrast, hyperglycemic correction with insulin in diabetic rats normalized expression of brain Kir6.2, reduced ischemic brain damage and restored neuroprotective effects of sevoflurane post-conditioning. Our findings suggest that decreased brain mitoKATP channel contributes to exacerbating ischemic brain injury and the failure of neuroprotection by anesthetic post-conditioning in diabetes. Insulin glycemic control in diabetes may restore the neuroprotective effects of anesthetic post-conditioning by modulation of brain mitoKATP channel.