Kawada Toru, Yamazaki Toji, Akiyama Tsuyoshi, Kitagawa Hirotoshi, Shimizu Shuji, Mizuno Masaki, Li Meihua, Sugimachi Masaru
Department of Cardiovascular Dynamics, Advanced Medical Engineering Center, National Cardiovascular Center Research Institute, Osaka, Japan.
Life Sci. 2008 Sep 26;83(13-14):490-5. doi: 10.1016/j.lfs.2008.07.013. Epub 2008 Jul 31.
To evaluate vagal stimulation-mediated myocardial protection against ischemia and reperfusion in in vivo ischemic myocardium.
We measured myocardial interstitial myoglobin levels in the ischemic region using a cardiac microdialysis technique in anesthetized and vagotomized cats. We occluded the left anterior descending coronary artery (LAD) for 60 min and reperfused it for 60 min (VX group, n = 6). The effects of bilateral vagal stimulation (10 V, 5 Hz, 1-ms pulse duration), initiated immediately after LAD occlusion, were examined (VS group, n = 6). To examine the involvement of phosphatidylinositol 3-kinase (PI3K), vagal stimulation was performed after pretreatment with a PI3K inhibitor wortmannin (0.6 mg/kg, i.v.) (VS-W group, n = 6). To examine the contribution of bradycardia, vagal stimulation was performed with fixed-rate ventricular pacing (VS-P group, n = 6).
The average myoglobin level during the ischemic period was 1170+/-141 in VX (in ng/ml, mean+/-SE), which was significantly attenuated in VS (466+/-87, P<0.05) and VS-W (613+/-124, P<0.05) but not in VS-P (953+/-203). Reperfusion increased the myoglobin level to 2500+/-544 in VX, whereas it was suppressed in VS (824+/-213, P<0.05) and VS-W (948+/-315, P<0.05) but not in VS-P (1710+/-253).
Vagal stimulation, initiated immediately after LAD occlusion, attenuated the myocardial injury. Moreover, bradycardia, independent of PI3K pathway, plays a significant role in vagally induced cardioprotection during acute myocardial ischemia.
评估迷走神经刺激介导的体内缺血心肌对缺血再灌注的心肌保护作用。
我们在麻醉且切断迷走神经的猫身上，使用心脏微透析技术测量缺血区域的心肌间质肌红蛋白水平。我们阻断左冠状动脉前降支（LAD）60分钟，然后再灌注60分钟（VX组，n = 6）。研究了LAD阻断后立即开始的双侧迷走神经刺激（10V，5Hz，1ms脉冲持续时间）的效果（VS组，n = 6）。为了研究磷脂酰肌醇3激酶（PI3K）的作用，在使用PI3K抑制剂渥曼青霉素（0.6mg/kg，静脉注射）预处理后进行迷走神经刺激（VS-W组，n = 6）。为了研究心动过缓的作用，在固定频率心室起搏下进行迷走神经刺激（VS-P组，n = 6）。
VX组缺血期肌红蛋白平均水平为1170±141（单位：ng/ml，均值±标准误），VS组（466±87，P<0.05）和VS-W组（613±124，P<0.05）显著降低，但VS-P组（953±203）未降低。再灌注使VX组肌红蛋白水平升高至2500±544，而VS组（824±213，P<0.05）和VS-W组（948±315，P<0.05）受到抑制，但VS-P组（1710±253）未受抑制。
LAD阻断后立即开始的迷走神经刺激减轻了心肌损伤。此外，与PI3K途径无关的心动过缓在急性心肌缺血期间迷走神经诱导的心脏保护中起重要作用。
