Dipyridamole Potentiates the Myocardial Infarct Size–Limiting Effect of Ischemic Preconditioning
Dipyridamole Potentiates the Myocardial Infarct Size–Limiting Effect of Ischemic Preconditioning
复制标题
双嘧达莫增强缺血预处理对心肌梗死面积的限制作用
DOI：
10.1161/01.cir.86.3.979
复制
发表时间：
1992
期刊：
影响因子：
37.8
通讯作者：
Osamu Limura
中科院分区：
文献类型：
--
作者：
T. Miura;T. Ogawa;T. Iwamoto;K. Shimamoto;Osamu Limura
研究背景近年来的研究表明，腺苷(ADO)受体激活在缺血预适应增强缺血耐受性中起关键作用。在这项研究中，我们旨在验证ADO转运抑制剂双嘧达莫增强预适应效应的假设。方法与结果6组兔冠状动脉结扎30min，再灌流72h。心肌梗死面积(IS)和危险面积(AR)分别由组织学和荧光颗粒测定。表示为OFAR百分比(%IS/AR)，对照组为46.5±3.4%(n=13)。缺血2分钟的预适应趋于限制%IS/AR(%IS/AR，35.5±3.5%，n=9)，这种保护作用可被ADO受体拮抗剂8-苯茶碱(8-PT)10 mg/kg(%IS/AR，43.9±5.8%，n=9)阻断。预适应2分钟前给予双嘧达莫(0.25 mg/kg)，可使%IS/AR显著降低至13.8±2.6%(n=12)，提示该药可增强预适应效应。此外，8-PT(%IS/AR，27.6±2.1%，n=11)可显著减弱潘生丁对心肌细胞预适应的增强作用。在缺血30分钟前给予潘生丁，不经预适应，不能降低IS/AR(55.3±5.2%，n=7)，本实验室先前的一项研究表明，目前剂量的8-PT不能改变兔的IS。结论潘生丁可明显增强预适应的心肌缺血限制作用。这一发现有力地支持了这样的假设，即在预适应缺血期间建立的内源性ADO刺激ADO受体，介导了预适应所提供的缺血耐受性的增加。
BackgroundRecent studies implicated a key role for adenosine (ADO) receptor activation in the enhancement of ischemic tolerance by ischemic preconditioning. In this study, we aimed to test the hypothesis that dipyridamole, an ADO transport inhibitor, enhances the preconditioning effect. Methods and ResultsSix groups of rabbits underwent 30-minute coronary occlusion and 72-hour reperfusion. Infarct size (IS) and the area-at-risk (AR) were determined by histology and by use of fluorescent particles, respectively. IS expressed as the percentage ofAR (%IS/AR) was 46.5±3.4% (n=13) in control rabbits. Preconditioning with 2-minute ischemia tended to limit %IS/AR (%IS/AR, 35.5±3.5%, n=9), and that possible protection was abolished by pretreatment with 10 mg/kg 8-phenyltheophylline (8–PT), an ADO receptor antagonist (%IS/AR, 43.9±5.8%, n=9). Administration of dipyridamole (0.25 mg/kg) before the 2-minute preconditioning markedly limited %IS/AR to 13.8±2.6% (n=12), indicating the potentiation of the preconditioning effect by this agent. Furthermore, this enhancement of preconditioning effect by dipyridamole treatment was significantly attenuated by 8-PT (%IS/AR, 27.6±2.1%, n=11). Dipyridamole given before the 30-minute ischemia, without preconditioning, did not reduce %IS/AR (55.3±5.2%, n=7), and a previous study from this laboratory had demonstrated that the present dose of 8–PT alone did not modify IS in the rabbit. ConclusionsDipyridamole significantly potentiated the IS-limiting effect of preconditioning. This finding strongly supports the hypothesis that stimulation of ADO receptors by endogenous ADO, which builds up during preconditioning ischemia, mediates the increased ischemic tolerance afforded by preconditioning.
影响因子：
20.1
作者：
MURRY, CE;RICHARD, VJ;JENNINGS, RB
通讯作者：
JENNINGS, RB