Feng Jianhua, Fischer Gregor, Lucchinetti Eliana, Zhu Min, Bestmann Lukas, Jegger David, Arras Margarete, Pasch Thomas, Perriard Jean-Claude, Schaub Marcus C, Zaugg Michael
Institute of Anesthesiology, University Hospital Zurich, Switzerland.
Anesthesiology. 2006 May;104(5):1004-14. doi: 10.1097/00000542-200605000-00017.
Postinfarct remodeled myocardium exhibits numerous structural and biochemical alterations. So far, it is unknown whether postconditioning elicited by volatile anesthetics can also provide protection in the remodeled myocardium.
Myocardial infarct was induced in male Wistar rats by ligation of the left anterior descending coronary artery. Six weeks later, hearts were buffer-perfused and exposed to 40 min of ischemia followed by 90 min of reperfusion. Anesthetic postconditioning was induced by 15 min of 2.1 vol% isoflurane. In some experiments, LY294002 (15 microM), a phosphatidylinositol 3-kinase inhibitor, was coadministered with isoflurane. Masson's trichrome staining, immunohistochemistry, Western blot analysis, and reverse-transcription polymerase chain reaction served to confirm remodeling. In buffer-perfused hearts, functional recovery was recorded, and acute infarct size was measured using 1% triphenyltetrazolium chloride staining and lactate dehydrogenase release during reperfusion. Western blot analysis was used to determine phosphorylation of reperfusion injury salvage kinases including protein kinase B/Akt and its downstream targets after 15 min of reperfusion.
Infarct hearts exhibited typical macroscopic and molecular changes of remodeling. Isoflurane postconditioning improved functional recovery and decreased acute infarct size, as determined by triphenyltetrazolium (35 +/- 5% in unprotected hearts vs. 8 +/- 3% in anesthetic postconditioning; P < 0.05) and lactate dehydrogenase release. This protection was abolished by LY294002, which inhibited phosphorylation of protein kinase B/Akt and its downstream targets glycogen synthase kinase 3beta, endothelial nitric oxide synthase, and p70S6 kinase.
Infarct-remodeled myocardium is receptive to protection by isoflurane postconditioning via protein kinase B/Akt signaling. This is the first time to demonstrate that anesthetic postconditioning retains its marked protection in diseased myocardium.
梗死后期重塑的心肌表现出众多结构和生化改变。迄今为止，尚不清楚挥发性麻醉药引发的后适应是否也能为重塑心肌提供保护。
通过结扎雄性Wistar大鼠左冠状动脉前降支诱导心肌梗死。六周后，心脏用缓冲液灌注，经历40分钟缺血，随后90分钟再灌注。通过给予15分钟2.1体积%异氟烷诱导麻醉后适应。在一些实验中，磷脂酰肌醇3激酶抑制剂LY294002（15微摩尔）与异氟烷共同给药。采用Masson三色染色、免疫组织化学、蛋白质印迹分析和逆转录聚合酶链反应来证实心肌重塑。在缓冲液灌注的心脏中，记录功能恢复情况，并使用1%氯化三苯基四氮唑染色和再灌注期间乳酸脱氢酶释放来测量急性梗死面积。蛋白质印迹分析用于确定再灌注15分钟后包括蛋白激酶B/Akt及其下游靶点在内的再灌注损伤挽救激酶的磷酸化情况。
梗死心脏表现出典型的宏观和分子重塑变化。异氟烷后适应改善了功能恢复并减小了急性梗死面积，通过氯化三苯基四氮唑测定（未保护心脏中为35±5%，麻醉后适应组为8±3%；P<0.05）以及乳酸脱氢酶释放情况得以证实。LY294002消除了这种保护作用，它抑制了蛋白激酶B/Akt及其下游靶点糖原合成酶激酶3β、内皮型一氧化氮合酶和p70S6激酶的磷酸化。
梗死重塑心肌对异氟烷通过蛋白激酶B/Akt信号通路进行的后适应保护敏感。这是首次证明麻醉后适应在患病心肌中仍保留其显著的保护作用。
