选择性腺苷 A3 受体刺激可减轻兔心脏的缺血性心肌损伤。

Selective adenosine A3 receptor stimulation reduces ischemic myocardial injury in the rabbit heart.

作者信息

Tracey W R, Magee W, Masamune H, Kennedy S P, Knight D R, Buchholz R A, Hill R J

机构信息

Department of Cardiovascular and Metabolic Diseases, Pfizer Inc., Groton, CT 06340, USA.

出版信息

Cardiovasc Res. 1997 Feb;33(2):410-5. doi: 10.1016/s0008-6363(96)00240-4.

DOI:10.1016/s0008-6363(96)00240-4

PMID:9074706

Abstract

OBJECTIVE

The aim of this study was to determine whether selective activation of the adenosine A3 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 (IA/AAR) to 19 +/- 4% (controls: 67 +/- 5%). Replacing global ischemia with 5 min perfusion of the rabbit A3-selective agonist, IB-MECA (A3 Ki: 2 nM; A1 Ki: 30 nM) elicited a concentration-dependent reduction in infarct size; 50 nM IB-MECA reduced IA/AAR to 24 +/- 4%. The A1-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 A1-selective antagonist, BWA1433 (50 nM), the IB-MECA-dependent cardioprotection was unaffected (28 +/- 6% IA/AAR). A non-selective (A1 vs. A3) concentration of BWA1433 (5 microM) significantly attenuated the IB-MECA-dependent cardioprotection (61 +/- 7% IA/AAR).

CONCLUSIONS

These data clearly demonstrate that selective A3 receptor activation provides cardioprotection from ischemia-reperfusion injury in the rabbit heart. Furthermore, the degree of A3-dependent cardioprotection is similar to that provided by A1 receptor stimulation or ischemic preconditioning.

摘要

目的

本研究旨在确定在心肌缺血-再灌注损伤的Langendorff模型中，腺苷A3受体的选择性激活是否能减小梗死面积。

方法

用缓冲液灌注的兔心脏经历30分钟的局部缺血和120分钟的再灌注。通过四氮唑染色测量梗死面积，并将其标准化为危险区域面积（IA/AAR）。

结果

5分钟全心缺血和10分钟再灌注预处理可将梗死面积（IA/AAR）减小至19±4%（对照组：67±5%）。用兔A3选择性激动剂IB-MECA（A3 Ki：2 nM；A1 Ki：30 nM）灌注5分钟替代全心缺血，可引起梗死面积的浓度依赖性减小；50 nM IB-MECA可将IA/AAR减小至24±4%。A1选择性激动剂R-PIA（25 nM）将IA/AAR减小至相似程度（21±6%）。然而，虽然兔A1选择性拮抗剂BWA1433（50 nM）可显著抑制R-PIA的心脏保护作用（IA/AAR为54±7%），但IB-MECA依赖的心脏保护作用未受影响（IA/AAR为28±6%）。非选择性（A1对A3）浓度的BWA1433（5 μM）可显著减弱IB-MECA依赖的心脏保护作用（IA/AAR为61±7%）。