七氟醚预处理对全膝关节置换术后止血带性缺血再灌注损伤的影响

目的:评价七氟醚预处理对全膝关节置换术后止血带性缺血再灌注损伤的影响。方法:择期在全麻下拟行单侧全膝关节置换术(TKA)的患者30例,随机分为2组(n=15):实验组(A组)和对照组(B组)。A组于止血带充气前吸入1MAC七氟醚30min,B组患者只吸入纯氧。测定并比较两组患者麻醉诱导前(T0)和止血带放气后30min(T1)、60min(T2)时的超氧化物歧化酶(SOD)活性及丙二醛(MDA)浓度,术后取股四头肌活检观测肌肉的病理改变。结果:T1、T2时两组MDA浓度明显高于T0时而SOD活性明显低于T0时,(P<0.05);A组于T1、T2时MDA浓度显著低于B组而SOD活性显著高于B组(P<0.05或P<0.01);B组病理切片示股四头肌溶解,大量中性粒细胞浸润;A组为正常肌肉组织。结论:七氟醚预处理可减轻TKA手术患者止血带诱发下肢缺血再灌注损伤,对骨骼肌有一定的保护作用。

Postconditioning of sevoflurane and propofol is associated with mitochondrial permeability transition pore

Background: Sevoflurane and propofol are effective cardioprotective anaesthetic agents, though the cardioprotection of propofol has not been shown in humans. Their roles and underlying mechanisms in anesthetic postconditioning are unclear. Mitochondrial permeability transition pore (MPTP) opening is a major cause of ischemia-reperfusion injury. Here we investigated sevoflurane- and propofol-induced postconditioning and their relationship with MPTP. Methods: Isolated perfused rat hearts were exposed to 40 min of ischemia followed by 1 h of reperfusion. During the first 15 min of reperfusion, hearts were treated with either control buffer (CTRL group) or buffer containing 20 μmol/L atractyloside (ATR group), 3% (v/v) sevoflurane (SPC group), 50 μmol/L propofol (PPC group), or the combination of atractyloside with respective anesthetics (SPC+ATR and PPC+ATR groups). Infarct size was determined by dividing the total necrotic area of the left ventricle by the total left ventricular slice area (percent necrotic area). Results: Hearts treated with sevoflurane or propofol showed significantly better recovery of coronary flow, end-diastolic pressures, left ventricular developed pressure and derivatives compared with controls. Sevoflurane resulted in more protective alteration of hemodynamics at most time point of reperfusion than propofol. These improvements were paralleled with the reduction of lactate dehydrogenase release and the decrease of infarct size (SPC vs CTRL: (17.48±2.70)% vs (48.47±6.03)%, P<0.05; PPC vs CTRL: (35.60±2.10)% vs (48.47±6.03)%, P<0.05). SPC group had less infarct size than PPC group (SPC vs PPC: (17.48±2.70)% vs (35.60±2.10)%, P<0.05). Atractyloside coadministration attenuated or completely blocked the cardioprotective effect of postconditioning of sevoflurane and propofol. Conclusion: Postconditioning of sevoflurane and propofol has cardio-protective effect against ischemia-reperfusion injury of heart, which is associated with inhibition of MPTP opening. Compared to propofol, sevoflurane provides superior protection of functional recovery and infarct size.

Sevoflurane Versus Propofol for Myocardial Protection in Patients Undergoing Coronary Artery Bypass Grafting Surgery: a Meta-analysis of Randomized Controlled Trials

Objective To systematically review randomized controlled trials to compare myocardial protection profiles of sevoflurane with propofol in patients undergoing coronary artery bypass grafting （CABG） surgery. Methods Electronic databases were searched to identify all randomized controlled trials comparing sevoflurane with propofol for protecting myocardium in adult patients undergoing CABG surgery. Two authors independently extracted patients＇ perioperative data, including patients＇ baseline characteristics, surgical variables, and outcome data. For continuous variables, treatment effects were calculated as weighted mean difference （WMD） and 95% confidential interval （C/）. For dichotomous data, treatment effects were calculated as odds ratio （OR） and 95% CI. Each outcome was tested for heterogeneity, and randomized-effects or fixed-effects model was used in the presence or absence of significant heterogeneity （Q test P〈0.05）. Sensitivity analyses were done by examining the influence of statistical model on estimated treatment effects. Publication bias was explored through visual inspection of funnel plots of the outcomes. Statistical significance was defined as P〈0.05. Results Our search yielded 13 studies including 696 patients, and 402 patients were allocated into sevoflurane group and 294 into propofol group. There was no significant difference in postoperative mechanical ventilation time, inotropic support, mortality, myocardial infarction, and atrial fibrillation between the two groups （all P〉0.05）. Patients randomized into sevoflurane group had higher post-bypass cardiac index （WMD=0.39, 95% CI： 0.18 to 0.60, P=0.0003）, lower troponin I level （WMD=-0.82, 95% CI：-0.87 to -0.85, P=0.0002）, lower incidence of myocardial ischemia （OR=0.37, 95% CI： 0.16 to 0.83, P=0.02）, shorter ICU and hospital stay length （WMD=-10.99, 95% CI： -12.97 to -9.01, P〈0.00001; WMD=-0.78, 95% CI： -1.00 to -0.56, P〈0.00001, respectively）. Conclusion This meta-analysis has found some evidence showing that sevoflurane has better myocardial protection than propofol in CABG surgery.

Effects of Sevoflurane on the discharges of wide dynamic range neurons in spinally transected rats

Objective: To study the effects of clinical concentration of sevoflurane on activity of wide dynamic range neurons. Methods: Eight Spraque-Dawley rats(male) were selected. Their spinal cords were exposed and transected at T 9-10 level. The rate of firings of single neurons in the dorsal horn in response to electrical stimulation of skin was recorded with microelectrodes. The early and late discharges were observed when rats inhaled 0.5%, 1.0%, 1.5%, and 2.0% sevoflurane. Results: Sevoflurane suppressed the early and late discharges at the concentration of 0.5%, 1.0%, 1.5%, and 2.0%. Compared with early discharges, the extent of inhibition of late discharges was wider at the concentration of 1%, 1.5%, and 2.0% of sevoflurane. Conclusion: It is indicated that sevoflurane could suppress the transmission of nociceptive and non-nociceptive stimulation at dorsal horn. The suppression on nociceptive imput is stronger than that on non-nociceptive imput when the concentration of sevoflurane is more than 1%.

Innovate combination of sevoflurane dilution in dimethyl sulfoxide: A stability study by gas chromatography and nuclear magnetic resonance

To investigate physicochemical stability of sevofuranein dimethyl sulfoxide using gas chromatography with a fame ionization detector and nuclear magnetic reso-nance （NMR）.METHODSUndiluted sevoflurane, plus dilutions 1：2, 1：5, 1：10, 1：25, and 1：50 in dimethyl sulfoxide were prepared in a vertical laminar fow cabinet class Ⅱ type B and stored at different temperatures （23 ℃, 6 ℃, and -10 ℃） for 45 d. Sterile 1 mL polypropylene amber syringes to minimize light degradation, caps and needles were used. The presence of sevofurane and its degradation products in the samples was determined by gas chroma-tography with flame ionization detector （260 ℃, 40min）, and by 1H, 19F, and proton-decoupled 19F nuclearmagnetic resonance.RESULTS The gas chromatography analysis showed sevofluraneand dimethyl sulfoxide （DMSO） retention times were 2.7and 13.0 min, respectively. Pure DMSO injection into thecolumn resulted in two additional peaks at 2.1 and 2.8min. The same sevofurane peak at 2.7 min was observedin all the dilutions at -10 ℃, 4 ℃ and 25 ℃. The NMRspectra showed signals consistent with the sevoflurane structure in all the dilutions at -10 ℃, 4 ℃ and 25 ℃. In the 1H spectrum, two signals corresponding to the sevoflurane molecule were observed at 5.12 and 4.16 parts per million （ppm5）. In the 19F-NMR spectrum, two signals were observed at -76.77 ppm and -157.13 ppm. In the 19F NMR CPD, two signals were observed at -76.77 ppm and -157.13 ppm. The first one showed a doublet （JF-F = 3.1 Hz） which integrated by six fluorine nuclei from the hexafluoro-isopropyl group. The second signal was integrated by a fuorine atom and showed a septuplet （JF-F = 3.1 Hz）.CONCLUSIONThis study shows that different concentrations ofsevofurane in dimethyl sulfoxide retain their chemicalcomposition after exposure to different temperaturesfor a period of 45 d.

Duplicate preconditioning with sevoflurane in vitro improves neuroprotection in rat brain via activating the extracellular signal-regulated protein kinase

Objective Sevoflurane preconditioning has been demonstrated to reduce cerebral ischemia–reperfusion（IR） injury,but the underlying mechanisms have not been fully elucidated.Besides,different protocols would usually lead to different results.The objective of this study was to determine whether dual exposure to sevoflurane improves the effect of anesthetic preconditioning against oxygen and glucose deprivation（OGD）injury in vitro.Methods Rat hippocampal slices under normoxic conditions（95%O2/5%CO2）were pre-exposed to sevoflurane 1,2 and 3 minimum alveolar concentration （MAC）for 30 min,once or twice,with 15-min washout after each exposure.The slices were then subjected to 13-min OGD treatment（95%N2/5%CO2,glucose-free）,followed by 30-min reoxygenation.The population spikes（PSs）were recorded in the CA1 region of rat hippocampus.The percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment was calculated,since it could indicate the recovery degree of neuronal function.In addition,to assess the role of mitogen-activated protein kinases（MAPKs）in preconditioning,U0126,an inhibitor of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）,and SB203580,an inhibitor of p38 MAPK,were separately added 10 min before sevoflurane exposure.Results Preconditioning once with sevoflurane 1,2,and 3 MAC increased the percentage of PS amplitude at the end of 30-min reoxygenation to that before OGD treatment,from（15.13±3.79）%（control）to（31.88±5.36）%, （44.00±5.01）%,and（49.50±6.25）%,respectively,and twice preconditioning with sevoflurane 1,2,and 3 MAC increased the percentage to（38.53±4.36）%,（50.74±7.05）%and（55.86±6.23）%,respectively.The effect of duplicate preconditioning with sevoflurane 3 MAC was blocked by U0126[（16.23±4.62）%].Conclusion Sevoflurane preconditioning can induce neuroprotection against OGD injury in vitro,and preconditioning twice enhances this effect.Besides,the activation of extracellular signal–regulated protein kinase（MEK-ERK1/2,ERK1/2 MAPK）may be involved in this process.