Selective adenosine A(3) receptor stimulation reduces ischemic myocardial injury in the rabbit heart
Selective adenosine A(3) receptor stimulation reduces ischemic myocardial injury in the rabbit heart
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DOI：
10.1016/s0008-6363(96)00240-4
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发表时间：
1997-02-01
影响因子：
10.8
通讯作者：
Hill, RJ
中科院分区：
文献类型：
--
作者：
Tracey, WR;Magee, W;Hill, RJ
目的：本研究的目的是确定选择性激活腺苷A(3)受体是否能减少心肌缺血-再灌注损伤的朗宁多夫模型的梗塞范围。方法：建立兔心脏局部缺血30min再灌流120min的模型。结果：全脑缺血5min再灌流10min预适应可使心肌梗死面积(ZA/AAR)降至19+/-4%(对照组：67+/-5%)。用兔A(3)选择性激动剂IB-MECA(A(3)K-I：2 nM；A(1)，K-I：30 nM)替代全脑缺血5min可引起浓度依赖性的心肌梗死面积缩小，50 nM IB-MECA使IA/AAR降至24+/-4%。A(1)选择性激动剂R-PIA(25 NM)对IA/AAR的抑制作用相似(21+/-6%)。然而，当R-PIA的心脏保护作用被兔A(1)选择性拮抗剂BWA1433(50 NM)显著抑制(54+/-7%IA/AAR)时，这种依赖IB-MECA的心脏保护作用不受影响(28+/-6%IA/AAR)。非选择性浓度(A(1)vs A(3))的BWA1433(5 MU M)显著减弱IB-MECA依赖的心脏保护作用(61+/-7%IA/AAR)。结论：这些数据清楚地表明，选择性激活A(3)受体对兔心脏缺血再灌注损伤具有保护作用。此外，A(3)依赖的心脏保护程度与A(1)受体刺激或缺血预适应所提供的程度相似。
Objective: The aim of this study was to determine whether selective activation of the adenosine A(3) receptor reduces infarct size in a Langendorff model of myocardial ischemia-reperfusion injury. Methods: Buffer-perfused rabbit hearts were exposed to 30 min regional ischemia and 120 min of reperfusion. Infarct size was measured by tetrazolium staining and normalized for area-at-risk (IA/AAR), Results: Preconditioning by 5 min global ischemia and 10 min reperfusion reduced infarct size (ZA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A(3)-selective agonist, IB-MECA (A(3) K-i: 2 nM; A(1), K-i: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A(1)-selective agonist, R-PIA (25 nM) reduced IA/AAR to a similar extent (21 +/- 6%). However, while the cardioprotective effect of R-PIA was significantly inhibited (54 +/- 7% IA/AAR) by the rabbit A(1)-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A(1) vs. A(3)) concentration of BWA1433 (5 mu M) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR). Conclusions: These data clearly demonstrate that selective A(3) receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A(3)-dependent cardioprotection is similar to that provided by A(1) receptor stimulation or ischemic preconditioning.