Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning.
Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning.
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腺苷 A1/A2a 受体激动剂 AMP-579 可诱导针对体内心肌顿抑的急性和延迟预处理。
DOI：
10.1152/ajpheart.00493.2004
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发表时间：
2004
期刊：
影响因子：
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通讯作者：
Lasley,RobertD
中科院分区：
文献类型：
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作者：
Kristo,Gentian;Yoshimura,Yukihiro;Keith,ByronJ;Stevens,RandyM;Jahania,SalikA;MentzerJr,RobertM;Lasley,RobertD
本研究的目的是确定腺苷A1/ a2受体激动剂AMP-579是否诱导急性和延迟的心肌休克预处理。在麻醉开胸猪冠状动脉闭塞15 min，再灌注3 h，产生局部休克。在急性保护研究中，动物分别在缺血前10分钟用生理盐水、低剂量AMP-579 （15 μg/kg静脉注射）或高剂量AMP-579 （50 μg/kg静脉注射，14 μg/kg静脉注射+ 1.2 μg·kg−1·min−1，冠状动脉闭塞前30分钟）进行预处理。在给药24 h后，观察高剂量AMP-579 （50 μg/kg iv）的延迟预处理效果。通过测量区域预载可回收冲程功（PRSW）和PRSW面积来评估负荷不敏感收缩力。急性预处理AMP-579剂量依赖性改善局部PRSW：高剂量组和低剂量组在RP 3 h分别为129±5%和100±2%，对照组为78±5%。腺苷a1受体拮抗剂8-环戊基-1,3-二丙基黄嘌呤（0.7 mg/kg）可阻断高剂量AMP-579的急性保护作用，表明这些作用是通过a1受体激活介导的。AMP-579延迟预处理显著增加PRSW区域的恢复：在RP 3 h时，64±5%比33±5%的对照组。在离体灌注大鼠心脏研究中，与其他腺苷受体激动剂相比，AMP-579 a1和a2受体介导的作用的起效和消退动力学是不同的。腺苷激动剂AMP-579的独特性质可能在其诱导延迟预适应对抗体内心肌休克的能力中发挥作用。
The purpose of this study was to determine whether the adenosine A1/A2areceptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning. Regional stunning was produced by 15 min of coronary artery occlusion and 3 h of reperfusion (RP) in anesthetized open-chest pigs. In acute protection studies, animals were pretreated with saline, low-dose AMP-579 (15 μg/kg iv bolus 10 min before ischemia), or high-dose AMP-579 (50 μg/kg iv at 14 μg/kg bolus + 1.2 μg·kg−1·min−1for 30 min before coronary occlusion). The delayed preconditioning effects of AMP-579 were evaluated 24 h after administration of saline vehicle or high-dose AMP-579 (50 μg/kg iv). Load-insensitive contractility was assessed by measuring regional preload recruitable stroke work (PRSW) and PRSW area. Acute preconditioning with AMP-579 dose dependently improved regional PRSW: 129 ± 5 and 100 ± 2% in high- and low-dose AMP-579 groups, respectively, and 78 ± 5% in the control group at 3 h of RP. Administration of the adenosine A1receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (0.7 mg/kg) blocked the acute protective effect of high-dose AMP-579, indicating that these effects are mediated through A1receptor activation. Delayed preconditioning with AMP-579 significantly increased recovery of PRSW area: 64 ± 5 vs. 33 ± 5% in control at 3 h of RP. In isolated perfused rat heart studies, kinetics of the onset and washout of AMP-579 A1and A2areceptor-mediated effects were distinct compared with those of other adenosine receptor agonists. The unique nature of the adenosine agonist AMP-579 may play a role in its ability to induce delayed preconditioning against in vivo myocardial stunning.