ATL 313, A Selective A2A Adenosine Receptor Agonist, Reduces Myocardial Infarct Size in a Rat Ischemia/Reperfusion Model

Wangde Dai, Sharon L Hale, Rohith Nayak, Robert A Kloner*
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

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© Dai et al.; Licensee Bentham Open

open-access license: This is an open access article licensed under the terms of the Creative Commons Attribution Non-Commercial License ( which permits unrestricted, non-commercial use, distribution and reproduction in any medium, provided the work is properly cited.

* Address correspondence to this author at the The Heart Institute, Good Samaritan Hospital, 1225 Wilshire Boulevard, Los Angeles, CA 90017; Tel: 213-977-4050; Fax: 213-977-4107; E-mail:



The cardioprotective effects of activation of the A2A adenosine receptor (A2AAR) on ischemia/reperfusion injury in the heart remain controversial. We investigated whether ATL 313, a new selective A2AAR 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.


A2AAR 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.

Keywords: Myocardial infarction, A2A adenosine receptor, ATL 313..