Journal article
Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning
American journal of physiology. Heart and circulatory physiology, v 287(6), pp H2746-H2753
Dec 2004
PMID: 15271662
Featured in Collection : UN Sustainable Development Goals @ Drexel
Abstract
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 microg/kg iv bolus 10 min before ischemia), or high-dose AMP-579 (50 microg/kg iv at 14 microg/kg bolus + 1.2 microg.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 microg/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.
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Details
- Title
- Adenosine A1/A2a receptor agonist AMP-579 induces acute and delayed preconditioning against in vivo myocardial stunning
- Creators
- Gentian Kristo - University of KentuckyYukihiro Yoshimura - University of KentuckyByron J Keith - University of KentuckyRandy M Stevens - University of KentuckySalik A Jahania - University of KentuckyRobert M Mentzer, JrRobert D Lasley - University of Kentucky
- Publication Details
- American journal of physiology. Heart and circulatory physiology, v 287(6), pp H2746-H2753
- Publisher
- American Physiological Society (APS)
- Grant note
- R01 HL-34759 / NHLBI NIH HHS R01 HL-66132 / NHLBI NIH HHS
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pediatrics
- Web of Science ID
- WOS:000225165700047
- Scopus ID
- 2-s2.0-16544392131
- Other Identifier
- 991021838711504721
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InCites Highlights
Data related to this publication, from InCites Benchmarking & Analytics tool:
- Web of Science research areas
- Cardiac & Cardiovascular Systems
- Peripheral Vascular Disease
- Physiology