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.

Expression of Bcl-2 and NF-κB in brain tissue after acute renal ischemia-reperfusion in rats

Objective:To investigate the effect of acute renal ischemia reperfusion on brain tissue.Methods:Fourty eight rats were randomly divided into four groups(n=12):sham operation group,30 min ischemia 60 min reperfusion group,60 min ischemia 60 min reperfusion group,and120 min ischemia 60 min reperfusion group.The brain tissues were taken after the experiment.TUNEL assay was used to detect the brain cell apoptosis,and western blot was used to detect the expression of apoptosis-related proteins and inflammatory factors.Results:Renal ischemiareperiusion induced apoptosis of brain tissues,and the apoptosis increased with prolongation of ischemia time.The detection at the molecular level showed decreased Bcl-2 expression,increased Bax expression,upreguiated expression of NF- κB and its downstream factor COX-2/PGE2.Conclusions:Acute renal ischemia-reperfusion can cause brain tissue damage,manifested as induced brain tissues apoptosis and inflammation activation.

Admission delay is associated with worse surgical outcomes for elderly hip fracture patients:A retrospective observational study

BACKGROUND:The influence of surgical delay on mortality and morbidity has been studied extensively among elderly hip fracture patients.However,most studies only focus on the timing of surgery when patients have already been hospitalized,without considering pre-admission waiting time.Therefore,the present study aims to explore the infl uence of admission delay on surgical outcomes.METHODS:In this retrospective study,we recorded admission timing and interval from admission to surgery for included patient.Other covariates were also collected to control confounding.The primary outcome was 1-year mortality.The secondary outcomes were 1-month mortality,3-month mortality,ICU admission and postoperative pneumonia.We mainly used multivariate logistic regression to determine the effect of admission timing on postoperative outcomes.An additional survival analysis was also performed to assess the impact of admission delay on survival status in the fi rst year after operation.RESULTS:The proportion of patients hospitalized on day 0,day 1,day 2 after injury was 25.4%,54.7%and 66.3%,respectively.And 12.6%patients visited hospital one week later after injury.Mean time from admission to surgery was 5.2 days(standard deviation 2.8 days).Hospitalization at one week after injury was a risk factor for 1-year mortality(OR 1.762,95%CI 1.026–3.379,P=0.041).CONCLUSION:Admission delay of more than one week is signifi cantly associated with higher 1-year mortality.As a supplement to the current guidelines which emphasizes early surgery after admission,we also advocate early admission once patients get injured.

Room temperature tensile deformation behavior of a Ni-based superalloy with high W content

K416B Ni-based superalloy with high W content has good high temperature properties and low cost,which has a great development potential.To investigate the room temperature tensile property and the deformation feature of K416B superalloy,tensile testing at room temperature was carried out,and optical microscopy (OM),scanning electron microscopy (SEM) and transmission electron microscopy (TEM) were used to analyze the deformation and damage mechanisms.Results show that the main room temperature tensile deformation features of the K416B nickel-based superalloy are dislocations slipping in the matrix and shearing into γ’ phase.The <110> super-dislocations shearing into γ’ phase can form the anti-phase boundary two coupled (a/2)<110> partial-dislocations or decompose into the configuration of two (a/3)<112> partial dislocations plus stacking fault.In the later stage of tensile testing,the slip-lines with different orientations are activated in the grain,causing the stress concentration in the regions of block carbide or the porosity,and cracks initiate and propagate along these regions.

Sevoflurane postconditioning reduces myocardial reperfusion injury in rat isolated hearts via activation of PI3K/Akt signaling and modulation of Bcl-2 family proteins

Sevoflurane postconditioning reduces myocardial infarct size.The objective of this study was to examine the role of the phosphatidylinositol-3-kinase(PI3K)/Akt pathway in anesthetic postconditioning and to determine whether PI3K/Akt signaling modulates the expression of pro-and antiapoptotic proteins in sevoflurane postconditioning.Isolated and perfused rat hearts were prepared first,and then randomly assigned to the following groups:Sham-operation(Sham),ischemia/reperfusion(Con),sevoflurane postconditioning(SPC),Sham plus 100 nmol/L wortmannin(Sham+Wort),Con+Wort,SPC+Wort,and Con+dimethylsulphoxide(DMSO).Sevoflurane postconditioning was induced by administration of sevoflurane(2.5%,v/v) for 10 min from the onset of reperfusion.Left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),maximum increase in rate of LVDP(+dP/dt),maximum decrease in rate of LVDP(?dP/dt),heart rate(HR),and coronary flow(CF) were measured at baseline,R30 min(30 min of reperfusion),R60 min,R90 min,and R120 min.Creatine kinase(CK) and lactate dehydrogenase(LDH) were measured after 5 min and 10 min reperfusion.Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion.Total Akt and phosphorylated Akt(phospho-Akt),Bax,Bcl-2,Bad,and phospho-Bad were determined by Western blot analysis.Analysis of variance(ANOVA) and Student-Newman-Keuls' test were used to investigate the significance of differences between groups.The LVDP,±dP/dt,and CF were higher and LVEDP was lower in the SPC group than in the Con group at all points of reperfusion(P<0.05).The SPC group had significantly reduced CK and LDH release and decreased infarct size compared with the Con group [(22.9±8)% vs.(42.4±9.4)%,respectively;P<0.05].The SPC group also had increased the expression of phospho-Akt,Bcl-2,and phospho-Bad,and decreased the expression of Bax.Wortmannin abolished the cardioprotection of sevoflurane postconditioning.Sevoflurane postconditioning may protect the isolated rat heart.Activation of PI3K and modulation of the expression of pro-and antiapoptotic proteins may play an important role in sevoflurane-induced myocardial protection.

Effects of sevoflurane preconditioning and postconditioning on rat myocardial stunning in ischemic reperfusion injury

Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting the severity of myocardial stunning. Therefore, we report the effects of sevofiurane preconditioning and postconditioning on stunned myocardium in isolated rat hearts. Isolated rat hearts were underwent 20 min of global ischemia and 40 min of reperfusion. After an equilibration period （20 min）, the hearts in the preconditioning group were exposed to sevoflurane for 5 min and next washout for 5 min before ischemia. Hearts in the sevoflurane postconditioning group underwent equilibration and ischemia, followed immediately by sevoflurane exposure for the first 5 min of reperfusion. The control group received no treatment before and after ischemia. Left ventricular pressure, heart rate, coronary flow, electrocardiogram, and tissue histology were measured as variables of ventricular function and cellular injury, respectively. There was no significant difference in the duration of reperfusion ventricular arrhythmias between control and sevoflurane preconditioning group （P=0.195）. The duration of reperfusion ventricular arrhythmias in the sevoflurane postconditioning group was significantly shorter than that in the other two groups （P〈0.05）. ＋（dPIdt）max in the sevoflurane preconditioning group at 5, 10, 15, 20, and 30 min after reperfusion was significantly higher than that in the control group （P〈0.05）, and there were no significant differences at 40 min after reperfusion among the three groups （P〉0.05）. As expected, for a 20-min general ischemia, infarct size in heart slices determined by 2,3,5-triphenyltetrazolium chloride staining among the groups was not obvious. Sevofiurane postconditioning reduces reperfusion arrhythmias without affecting the severity of myocardial stunning. In contrast, sevoflurane preconditioning has no beneficial effects on reperfusion arrhythmias, but it is in favor of improving ventricular function and recovering myocardial stunning. Sevoflurane preconditioning and postconditioning may be useful for correcting the stunned myocardium.

Activation of Akt and cardioprotection against reperfusion injury are maximal with only five minutes of sevoflurane postconditioning in isolated rat hearts

It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo.Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion(I/R) injury.Adult male Sprague-Dawley rats were randomly divided into six groups(n=12):a sham-operation group,an I/R group,and four sevoflurane postconditioning groups(S2,S5,S10,and S15).In the S2,S5,S10,and S15 groups,the duration times of sevoflurane administration were 2,5,10,and 15 min after the onset of reperfusion,respectively.The isolated rat hearts were mounted on the Langendorff system,and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion.Left ventricular(LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30,60,90,and 120 min of reperfusion were analyzed.Myocardial infarct size at the end of reperfusion(n=7 in each group) and the expression of myocardial phosphorylated Akt(p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts(n=5 in each group).Compared with the I/R group,the S5,S10,and S15 groups had significantly improved left ventricular end-diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),and the maximal rate of rise or fall of the LV pressure(±dP/dtmax),and decreased myocardial infarct size(P<0.05),but not the S2 group.After 15 min of reperfusion,the expression of p-Akt was markedly up-regulated in the S5,S10,and S15 groups compared with that in the I/R group(P<0.05),but not in the S2 group.Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.

Cisplatin combined with hyperthermia kills HepG2 cells in intraoperative blood salvage but preserves the function of erythrocytes

The safe use of intraoperative blood salvage （IBS） in cancer surgery remains controversial. Here, we investigated the kil ing effect of cisplatin combined with hyperthermia on human hepatocarcinoma （HepG2） cel s and erythrocytes from IBS in vitro. HepG2 cel s were mixed with concentrated erythrocytes and pretreated with cisplatin （50, 100, and 200μg/ml） alone at 37 °C for 60 min and cisplatin （25, 50, 100, and 200μg/ml） combined with hyperthermia at 42 °C for 60 min. After pretreatment, the cel viability, colony formation and DNA metabolism in HepG2 and the Na＋-K＋-ATPase activity, 2,3-diphosphoglycerate （2,3-DPG） concentration, free hemoglobin （Hb） level, osmotic fragility, membrane phosphatidylserine externalization, and blood gas variables in erythrocytes were determined. Pretreatment with cisplatin （50, 100, and 200μg/ml） combined with hyperthermia （42 °C） for 60 min significantly decreased HepG2 cel viability, and completely inhibited colony formation and DNA metabolism when the HepG2 cel concentration was 5×104 ml？1 in the erythrocyte （P0.05）. In conclusion, pre-treatment with cisplatin （50μg/ml） combined with hyperthermia （42 °C） for 60 min effectively eliminated HepG2 cel s from IBS but did not significantly affect erythrocytes in vitro.