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Am J Physiol Heart Circ Physiol 287: H2746-H2753, 2004. First published July 22, 2004; doi:10.1152/ajpheart.00493.2004
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Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning

Gentian Kristo, Yukihiro Yoshimura, Byron J. Keith, Randy M. Stevens, Salik A. Jahania, Robert M. Mentzer, Jr., and Robert D. Lasley

Department of Surgery, University of Kentucky College of Medicine, Lexington, Kentucky 40536-0298

Submitted 27 May 2004 ; accepted in final form 19 July 2004

The purpose of this study was to determine whether the adenosine A1/A2a receptor 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–1 for 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 A1 receptor 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 A1 receptor 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 A1 and A2a receptor-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.

adenosine receptors; ischemia-reperfusion


Address for reprint requests and other correspondence: R. D. Lasley, Dept. of Surgery, Univ. of Kentucky College of Medicine, 800 Rose St., Lexington, KY 40536-0298 (E-mail: rlasley{at}uky.edu)




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