Dai Wangde, Hale Sharon L, Nayak Rohith, Kloner Robert A
The Heart Institute of Good Samaritan Hospital, And Division of Cardiovascular Medicine of the Keck School of Medicine, University of Southern California, Los Angeles, California 90017-2395, USA.
Open Cardiovasc Med J. 2009 Nov 25;3:166-72. doi: 10.2174/1874192400903010166.
The cardioprotective effects of activation of the A(2A) adenosine receptor (A(2A)AR) on ischemia/reperfusion injury in the heart remain controversial. We investigated whether ATL 313, a new selective A(2A)AR agonist, could reduce myocardial infarct size in a rat ischemia/reperfusion model.
Sprague-Dawley rats were subjected to a 40 minute occlusion of the left coronary artery followed by 3 hours reperfusion. Hemodynamics were monitored during the procedure. The rats were divided into 3 groups: Group 1 received continuous intravenous infusion of saline given 10 min prior to ischemia and throughout reperfusion (n=8); Group 2 received continuous intravenous infusion of 10 ng/kg/min of ATL 313 given 10 min prior to ischemia, and throughout reperfusion (n=8); and group 3 received an intravenous bolus of ATL 313 (900 ng/Kg body weight) given 10 min prior to ischemia, and continuous intravenous infusion of 10 ng/kg/min of ATL 313 started at 20 min after ischemia and throughout reperfusion (n=8). After euthanasia of the rats, the hearts were harvested for the assessment of risk zone and zone of necrosis of the left ventricle.
The percentage of risk zone in the left ventricle was similar among group 1 (47 +/- 3.7 %), group 2 (41.5 +/- 4.2 %) and group 3 (42.4 +/- 3.8 %). However, the infarct size, expressed as a percentage of the risk zone, was significantly decreased in group 3 (30.6 +/- 5 %, P=0.01) compared with group 1 (53.8 +/- 6.2 %) and group 2 (52.1 +/- 4.8 %). In group 3, the bolus injection of ATL 313 caused a reduction in blood pressure during the procedure, and decreased heart rate and LV +/-dp/dt before coronary artery occlusion; but increased LV +dp/dt at the end of reperfusion compared to the other 2 groups.
A(2A)AR agonist ATL313 significantly reduced infarct size and improved LV contractility at the end of reperfusion assessed by LV dp/dt at a dose of 900 ng/Kg. The mechanisms for the observed cardioprotection effect of ATL313 remain to be determined.
A(2A) 腺苷受体（A(2A)AR）激活对心脏缺血/再灌注损伤的心脏保护作用仍存在争议。我们研究了新型选择性A(2A)AR激动剂ATL 313是否能在大鼠缺血/再灌注模型中减小心肌梗死面积。
将Sprague-Dawley大鼠左冠状动脉闭塞40分钟，然后再灌注3小时。在此过程中监测血流动力学。大鼠分为3组：第1组在缺血前10分钟及整个再灌注期间持续静脉输注生理盐水（n = 8）；第2组在缺血前10分钟及整个再灌注期间持续静脉输注10 ng/kg/min的ATL 313（n = 8）；第3组在缺血前10分钟静脉推注ATL 313（900 ng/Kg体重），并在缺血20分钟后开始及整个再灌注期间持续静脉输注10 ng/kg/min的ATL 313（n = 8）。大鼠安乐死后，取出心脏评估左心室的危险区和坏死区。
第1组（47 ± 3.7%）、第2组（41.5 ± 4.2%）和第3组（42.4 ± 3.8%）左心室危险区百分比相似。然而，与第1组（53.8 ± 6.2%）和第2组（52.1 ± 4.8%）相比，第3组以危险区百分比表示的梗死面积显著减小（30.6 ± 5%，P = 0.01）。在第3组中，推注ATL 313导致术中血压降低，冠状动脉闭塞前心率和左心室±dp/dt降低；但与其他2组相比，再灌注结束时左心室 +dp/dt增加。
A(2A)AR激动剂ATL313以900 ng/Kg的剂量显著减小梗死面积，并通过左心室dp/dt评估在再灌注结束时改善左心室收缩力。ATL313观察到的心脏保护作用机制仍有待确定。
