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  • 1
    ISSN: 1573-7241
    Keywords: adenosine ; A1 receptor agonist ; GR79236 ; infarct size ; ischemia-reperfusion ; reperfusion injury
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Adenosine A1 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 A1 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 A1 receptor agonist GR79236 (10.5 μg/kg, a dose shown to limit infarction in this model when given before ischemia) or vehicle were 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 cm3 vs 1.00 ± 0.05 cm3, 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 A1 receptor activation does not modify lethal reperfusion injury in myocardium.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1435-1803
    Keywords: Key words Ischemia – preconditioning – 8-(p-sulfophenyl)theophylline – ST segments – tyramine
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Attenuation of S-T segment elevation between the first and subsequent balloon inflations of a coronary angioplasty procedure has been assumed to indicate a transition to a preconditioned state, but there has been no validation of this assumption. Open-chest rabbits were instrumented with a coronary snare and epicardial electrode. The coronary artery was occluded twice for 5 min with each occlusion followed by 10 min of reflow before a final 30 min occlusion. The evolving S-T elevation was quantitated as the voltage-time integral. For the first coronary occlusion total S-T segment elevation averaged 40.8±5.4 mV·min, significantly greater than 26.2±4.6 mV·min for the second occlusion (p 〈 0.001). There was no further change during the initial 5 min of the third occlusion (42.5±4.5 mV·min). When the protection of ischemic preconditioning was blocked by intravenous infusion of 8-(p-sulfophenyl)theophylline, an adenosine receptor antagonist, attenuation of S-T segment elevation was no longer apparent. When preconditioning was pharmacologically triggered by tyramine rather than ischemia, there also was no alteration in S-T segment elevation among the 3 occlusions. Therefore, S-T elevation was diminished during the second episode of ischemia only when a transition occurred from non-preconditioned to preconditioned state between occlusions. An attenuated S-T segment is a valid marker for the presence of the preconditioned state.
    Type of Medium: Electronic Resource
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