The influence of anesthetics on cardioprotection by stress-induced protein

麻醉药对应激诱导蛋白心脏保护作用的影响

• 批准号: 13671587
• 负责人: KITAHATA Hiroshi
• 金额: $ 2.3万
• 依托单位: The University of Tokushima
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 2001
• 资助国家: 日本
• 起止时间: 2001 至 2002
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-13671587/
• 关键词: Heat-shock protein; Ischemic preconditioning; Myocardial tissue characterization; Integrate backscatter; Myocardial protection; Geranygernylacetone; Myocardial infarction

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

本实验采用家兔在体模型研究了抗溃疡药物香叶基香叶基丙酮（GGA）对热休克蛋白70家族的诱导作用。同时观察了麻醉药对GGA心肌保护作用的影响。用氯化三苯基四氮唑和伊文思蓝染色法测量缺血区面积和梗死灶大小。采用背向散射积分（IBS）技术检测左室短轴切面心肌组织的周期性变化（MCV），评价心肌组织超微结构的完整性。[2001]在实验前12小时和临实验前静脉注射1 mg/kg GGA（GGA组，n=6）。缺血预处理组（n=8）行2次冠状动脉前外侧阻断，间隔5 min，再灌注15 min。所有组均行冠状动脉阻断30 min，然后再灌注180 min。GG中的实际大小与风险面积的比值 ...更多信息 A组和IP组（36.6^^+__-17.9%，31.3^^+__-9.1%）显著低于对照组（59.2^^+__-18.3%，n=7）。冠脉闭塞后各组MCV均显著降低，但各组间无显著性差异。[2002]在实验前24小时静脉内给予溶媒或10 mg/kg剂量的GGA（GGA组，n=8，溶媒组，n=7）。GGA+5 HD组（n=8）在GGA预处理后，于冠脉阻断前30 min给予线粒体ATP敏感性钾<ATP>通道阻断剂5-羟基癸酸钠（5 mg/kg）。GGA+SEV组（n=8）在冠脉阻断前60 min给予七氟醚（0.5 MAC），持续30 min，各组均行冠脉阻断30 min，再灌注180 min。GGA组和GGA+SEV组的梗死面积与危险面积之比（38.5^^+__-9.9%，26.9^^+__-19.7%）显著低于溶剂组和GGA+5 HT组（59.2^^+_-9.4%，55.2^^+_-13.7%）。GGA的心肌保护作用可能与线粒体钾通道有关<ATP>。少

项目成果

Hiroshi Kitahata: "Effects of Ischemic Preconditioning on the Ultrasonic Myocardial Tissue Characterization and the Left Ventricular Work Efficiency during Sevoflurane Anesthesia in Canine Stunned Myocardium."Anesthesiology. 95 Suppl. A674 (2001)

Hiroshi Kitahata：“缺血预处理对犬震慑心肌七氟烷麻醉期间超声心肌组织特征和左心室工作效率的影响。”麻醉学。

Takashi Kawano, et al.: "Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes"Anesthesiology. 96. 1472-1477 (2002)

Takashi Kawano 等人：“临床相关浓度的丙泊酚对大鼠心室肌细胞中三磷酸腺苷敏感的钾通道没有影响”麻醉学。

Takashi Kawano, et al.: "Clinically relevant concentrations of propofol have no effect on adenosine triphosphate-sensitive potassium channels in rat ventricular myocytes."Anestheiology. 96. 1472-1477 (2002)

Takashi Kawano 等人：“临床相关浓度的丙泊酚对大鼠心室肌细胞中三磷酸腺苷敏感的钾通道没有影响。”麻醉学。

Hiroshi Kitahata, et al.: "Effects of ischemic preconditioning on the ultrasonic myocardial tissue characterization and the left ventricular work efficiency during sevoflurane anesthesia in canine stunned myocardium"Anesthesiology. 95. A-674 (2001)

Hiroshi Kitahata 等人：“犬震慑心肌七氟醚麻醉期间缺血预处理对超声心肌组织特征和左心室工作效率的影响”麻醉学。

Hiroshi Kitahata, et al.: "Effects of ischemic preconditioning on the ultrasonic myocardial tissue characterization and the left ventricular work efficiency during sevoflurane anesthesia in canine stunned myocardium."Anestheiology. 95. A-674 (2001)

Hiroshi Kitahata 等人：“在犬震慑心肌七氟醚麻醉期间，缺血预处理对超声心肌组织特征和左心室工作效率的影响。”麻醉学。