The influence of anesthetics on cardioprotection by stress-induced protein

采用家兔体内模型，研究了有报道的诱导热休克蛋白70家族的抗溃疡药物香叶乙酸酮（geranylgeranylacetone， GGA）是否具有心肌保护作用。同时评价了麻醉药对GGA心脏保护作用的影响。采用氯化三苯四唑和埃文斯蓝染色法测定大鼠缺血面积和缺血危险面积。获得左心室短轴视野水平的综合后向散射（IBS）图像，并利用IBS的循环变化幅度（MCV）评估心肌组织超微结构完整性。[2001]GGA组分别于实验前12 h和刚开始时静脉滴注GGA 1 mg/kg （n=6）。缺血预处理（IP）组（n=8）进行两次5分钟的冠状动脉前外侧闭塞，穿插15分钟的再灌注。各组冠脉闭塞30 min，再灌注180 min。GG . More A组和IP组的实际大小与危险面积之比（36.6^^+_ -17.9%,31.3^^+_ -9.1%）显著低于对照组（59.2^^+_ -18.3%,n=7）。冠状动脉闭塞后各组MCV均显著降低，但各组间无显著差异[2002]。实验前24 h静脉给予GGA或载药组，剂量为10 mg/kg （GGA组，n=8，载药组，n=7）。经GGA预处理后，GGA+5HD组（n=8）在冠状动脉闭塞前30 min给予线粒体三磷酸腺苷敏感钾（K_<ATP>）通道阻滞剂5-羟乙酸钠（5mg/kg）。GGA+SEV组（n=8），闭塞前60 min给予七氟醚（0.5 MAC），持续30 min，各组冠脉闭塞30 min，再灌注180 min。GGA和GGA+SEV组梗死面积与危险面积之比（38.5^^+_ -9.9%,26.9^^+_ -19.7%）明显低于对照组和GGA+5HT组（59.2^^+_ -9.4%,55.2^^+_ -13.7%）。GGA与IP一样具有心肌保护作用，吸入七氟醚可增强GGA的心肌保护作用。gga诱导心脏保护的机制可能与线粒体K_<ATP>通道有关。少

Whether geranylgeranylacetone (GGA), an antulcer drug reported to induce the heat-shock protein 70 family, may produce mycardial protection was inverstigated using an in vivo model of rabbit. The influence of anesthetics on cardioprotection by GGA was also evaluated. The infact size and the area at risk of ischemia were measured by triphenyltetrazolium chloride and Evans blue dyeing. Integrated backscatter (IBS) images of left ventricular short-axis view level were obtained and myocardial tissue ultrastrucural integrity was evaluated using the magnitudes of cyclic variation of IBS (MCV).[2001] Each of 1 mg/kg GGA was intravenously administered 12 hrs before and just before experiment (GGA group, n=6). The ischemic preconditioning (IP) group (n=8) was preteated with two 5-min anterolateral coronary occlusions interspersed with 15-min periods of reperfusion. All groups underwent 30 min of coronary occlusion, followed by 180 min of reperfusion. The ratios of infact size to risk area in GG … More A and IP groups (36.6^^+__-17.9%, 31.3^^+__-9.1%) were significantly lower than that in control group (59.2^^+__-18.3%, n=7). MCV significantly decreased after coronary occlusion in all groups, however there was no significant differenca between each group.[2002] Vehicle or GGA at a dose of 10 mg/kg was intravenously given 24 hrs before experiment (GGA group, n=8, vehicle group, n=7). After pretreatment with GGA, GGA+5HD group (n=8) received the mitochondrial adenosine triphoshate-sensitive potassium (K_<ATP>) channel blocker, sodium 5-hydroxydecanote (5mg/kg) 30 min before coronary occlusion. In GGA+SEV group (n=8), sevoflurane (0.5 MAC) was administered 60 min before occlusion and continued for 30 min. all groups underwent 30 min of coronary occlusion, followed by 180 min of reperfusion. The ratios of infarct size to risk area in GGA and GGA+SEV groups (38.5^^+__-9.9%, 26.9^^+__-19.7%) were significantly lower compared with those in vehicle and GGA+5HT groups (59.2^^+__-9.4%, 55.2^^+__-13.7%).GGA produced myocardial protection as IP, which was enhanced with sevoflurane inhalation. The mechanism of GGA-induced cardioprotection may involve the mitochondrial K_<ATP> channel. Less