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 postcon...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, sevofluran展开更多
Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. Howe...Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning （SpostC） in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase （PI3K）, extracellular signal-regulated kinase 1 and 2 （ERK 1/2）, mitochondrial KATP channels （mitOKAme） and mitochondrial permeability transition pore （mPTP）, by selectively inhibiting PI3K, ERK 1/2, mitOKATP, with LY294002 （LY）, PD98059 （PD）, 5-hydroxydecanoate （5-HD） and by directly opening of mPTP with atractyloside （ATR）, respectively. Methods Isolated rat hearts were randomly assigned to one of the 12 groups （n=-15）： Time control （continuous perfusion）, ISCH （30 minutes of ischemia followed by 60 minutes of reperfusion alone）, SpostC （3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia）, ISCH＋LY, ISCH＋PD, ISCH＋ATR, ISCH＋5-HD and ISCH＋ dimethyl sulfoxide （DMSO） groups （LY, PD, ATR, 5-HD and DMSO （the vehicle） was administered respectively during the first 15 minutes of reperfusion following test ischemia）, SpostC＋LY, SpostC＋PD, SpostC＋ATR and SpostC＋5-HD groups （LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively）. Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride （TTC） staining. Lactate dehydrogenase （LDH）, creatine kinase-MB （CK-MB） and cardiac troponin I （cTnl） released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD＋ content in myocardium, a marker of mPTP o展开更多
基金Project supported by the National Natural Science Foundation ofChina (No. 30772090)the Natural Science Foundation of ZhejiangProvince (No. Y204141)+2 种基金the Foundation from Science and Technology Department of Zhejiang Province (No. 2007R10034)theFoundation from Personnel Department of Zhejiang Province (NoJ20050046)the Foundation from Health Department of ZhejiangProvince (No. 2007QN007), China
文摘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, sevofluran
文摘Background Studies suggested that anesthetics administered upon the early reperfusion or ＂anesthetic postconditioning＂ could protect post-ischemic hearts against myocardial ischemia reperfusion injury （MIRI）. However, the mechanism responsible for such protection was not well-elucidated. We investigated the cardioprotection induced by sevoflurane postconditioning （SpostC） in rat hearts in vitro, and the respective role of phosphatidylinositol-3-kinase （PI3K）, extracellular signal-regulated kinase 1 and 2 （ERK 1/2）, mitochondrial KATP channels （mitOKAme） and mitochondrial permeability transition pore （mPTP）, by selectively inhibiting PI3K, ERK 1/2, mitOKATP, with LY294002 （LY）, PD98059 （PD）, 5-hydroxydecanoate （5-HD） and by directly opening of mPTP with atractyloside （ATR）, respectively. Methods Isolated rat hearts were randomly assigned to one of the 12 groups （n=-15）： Time control （continuous perfusion）, ISCH （30 minutes of ischemia followed by 60 minutes of reperfusion alone）, SpostC （3% sevoflurane postconditioning was administered during the first 15 minutes of reperfusion after 30 minutes of ischemia）, ISCH＋LY, ISCH＋PD, ISCH＋ATR, ISCH＋5-HD and ISCH＋ dimethyl sulfoxide （DMSO） groups （LY, PD, ATR, 5-HD and DMSO （the vehicle） was administered respectively during the first 15 minutes of reperfusion following test ischemia）, SpostC＋LY, SpostC＋PD, SpostC＋ATR and SpostC＋5-HD groups （LY, PD, ATR and 5-HD was coadministered with 3% sevoflurane, respectively）. Hemodynamics was compared within and between groups. Infarction size was determined at the end of experiments using triphenyltetrazolium chloride （TTC） staining. Lactate dehydrogenase （LDH）, creatine kinase-MB （CK-MB） and cardiac troponin I （cTnl） released from necrotic myocardium, were compared among TC, ISCH and SpostC groups. To investigate the relationships between RISK and mPTP implicated in SpostC, NAD＋ content in myocardium, a marker of mPTP o
