N-acetylcysteine restores isoflurane-induced preconditioning against myocardial infarction during hyperglycemia
N-acetylcysteine restores isoflurane-induced preconditioning against myocardial infarction during hyperglycemia
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DOI：
10.1097/00000542-200306000-00013
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发表时间：
2003-06-01
期刊：
影响因子：
8.8
通讯作者：
Kersten, JR
中科院分区：
文献类型：
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作者：
Kehl, F;Krolikowski, JG;Kersten, JR
背景：高血压可产生活性氧并阻止异氟醚诱导的预适应。作者测试的假设，清除活性氧与N-乙酰半胱氨酸将恢复对心肌梗死产生的保护异氟烷invivo.Methods：巴比妥麻醉犬（n = 45）的全身血流动力学的测量仪器。分别用三苯基四氮唑染色法和放射性微球法测定心肌梗死面积和冠状动脉侧支血流量。所有的狗进行了60分钟的左前降支冠状动脉闭塞，然后3小时的再灌注。在6个实验组中，在不存在或存在异氟烷（1.0最小肺泡浓度）的情况下，将犬随机分配接受0.9%生理盐水或15%葡萄糖水溶液输注，以将血糖浓度增加至600 mg/dl（高血糖症），并使用或不使用N-乙酰半胱氨酸（150 mg/kg IV）进行预处理。停止异氟烷，并允许血糖浓度恢复到基线值前左前降支冠状动脉occlusion.Results：心肌梗死面积为27 +/- 2%（n = 8）的左心室面积在对照实验中的风险。异氟烷显着（P < 0.05）减少了梗死面积（13 +/- 2%; n = 7）。单独的高氟醚不能改变梗死面积（29 +/- 3%; n = 7），但可消除异氟醚的保护作用（25 +/- 2%; n = 8）。单独使用N-乙酰半胱氨酸不影响梗死面积（28 +/- 2%; n = 8），但在高血糖期间恢复了异氟醚诱导的心脏保护作用（10 +/- 1%; n = 7）。结论：急性高血糖消除了异氟醚引起的心肌梗死面积减少，但N-乙酰半胱氨酸恢复了这些有益作用。结果表明，过量的活性氧在高血糖期间产生损害异氟醚诱导的预处理犬。
Background: Hyperglycemia generates reactive oxygen species and prevents isoflurane-induced preconditioning. The authors tested the hypothesis that scavenging reactive oxygen species with N-acetylcysteine will restore protection against myocardial infarction produced by isoflurane in vivo.Methods: Barbiturate-anesthetized dogs (n = 45) were instrumented for measurement of systemic hemodynamics. Myocardial infarct size and coronary collateral blood flow were measured with triphenyltetrazolium staining and radioactive microspheres, respectively. All dogs were subjected to a 60-min left anterior descending coronary artery occlusion followed by 3 h of reperfusion. Dogs were randomly assigned to receive an infusion of 0.9% saline or 15% dextrose in water to increase blood glucose concentrations to 600 mg/dl (hyperglycemia) in the absence or presence of isoflurane (1.0 minimum alveolar concentration) with or without pretreatment with N-acetylcysteine (150 mg/kg IV) in six experimental groups. Isoflurane was discontinued, and blood glucose concentrations were allowed to return to baseline values before left anterior descending coronary artery occlusion.Results: Myocardial infarct size was 27 +/- 2% (n = 8) of the left ventricular area at risk in control experiments. Isoflurane significantly (P < 0.05) decreased infarct size (13 +/- 2%; n = 7). Hyperglycemia alone did not alter infarct size (29 +/- 3%; n = 7) but abolished the protective effect of isoflurane (25 +/- 2%; n = 8). N-Acetylcysteine alone did not affect infarct size (28 +/- 2%; n = 8) but restored isoflurane-induced cardioprotection during hyperglycemia (10 +/- 1%; n = 7).Conclusions: Acute hyperglycemia abolishes reductions in myocardial infarct size produced by isoflurane, but N-acetylcysteine restores these beneficial effects. The results suggest that excessive quantities of reactive oxygen species generated during hyperglycemia impair isoflurane-induced preconditioning in dogs.