Baxter, GF and Hale, SL and Miki, T and Kloner, RA and Cohen, MV and Downey, JM and Yellon, DM (2000) Adenosine A(1) agonist at reperfusion trial (AART): Results of a three-center, blinded, randomized, controlled experimental infarct study. CARDIOVASC DRUG THER , 14 (6) 607 - 614.
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Adenosine A(1) receptor agonists given prior to myocardial ischemia limit ischemic injury in several species. However, the ability of adenosine receptor agonists to limit infarct size when given at reperfusion has proved controversial. We designed a three-center experimental study using a blinded, randomized treatment protocol to test the hypothesis that adenosine A(1) receptor activation during early reperfusion can attenuate lethal reperfusion injury, thereby reducing infarct size. Sixty anesthetized rabbits (20 in each laboratory) underwent 30 minutes coronary artery occlusion followed by 120 minutes reperfusion. The selective adenosine Ar receptor agonist GR79236 (10.5 mug/kg, a dose shown to limit infarction in this model when given before ischemia) or vehicle mere administered IV 10 minutes before reperfusion. Infarct size was assessed by tetrazolium staining and, after the randomization code was revealed, data from the three laboratories were pooled for statistical analysis. Infarct size was not modified by administration of GR79236. In the vehicle-treated group, the infarct-to-risk ratio was 28.9 +/- 2.7% (n = 24) compared with 31.9 +/- 2.6% (n = 26) in the GR79236-treated group (not significant). Risk zone volume was similar in the two groups (1.06 +/- 0.05 cm(3) vs 1.00 +/- 0.05 cm(3), respectively). A modest reduction in rate-pressure product was noted following the administration of GR79236, but; this effect was transient. The same dose of GR79236 was found to limit infarct size when given prior to coronary artery occlusion. We conclude that A(1) receptor activation does not modify lethal reperfusion injury in myocardium.
|Title:||Adenosine A(1) agonist at reperfusion trial (AART): Results of a three-center, blinded, randomized, controlled experimental infarct study|
|Keywords:||adenosine, A(1) receptor agonist, GR79236, infarct size, ischemia-reperfusion, reperfusion injury, ISOLATED RAT-HEART, MYOCARDIAL REPERFUSION, INTRACORONARY ADENOSINE, INTRAVENOUS ADENOSINE, ENDOGENOUS ADENOSINE, RECEPTOR AGONIST, SIZE-REDUCTION, INJURY, ISCHEMIA, MODEL|
|UCL classification:||UCL > School of Life and Medical Sciences > Faculty of Medical Sciences > Surgery and Interventional Science (Division of) > Institute of Orthopaedics and Musculoskeletal Science|
UCL > School of Life and Medical Sciences > Faculty of Population Health Sciences > Institute of Cardiovascular Science
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