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  • A1 receptor agonist  (1)
  • Key words Free radicals – N-2-mercaptopropionyl glycine – myocardial infarction – preconditioning – triphenyltetrazolium chloride  (1)
  • 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
    Electronic Resource
    Electronic Resource
    Springer
    Basic research in cardiology 94 (1999), S. 180-187 
    ISSN: 1435-1803
    Keywords: Key words Free radicals – N-2-mercaptopropionyl glycine – myocardial infarction – preconditioning – triphenyltetrazolium chloride
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract Recent studies have repoarted that prolonged infusion of N-2-mercaptopropionyl glycine (MPG), a diffusible antioxidant, could limit infarct size in dogs. However, there are no comparable studies testing this agent in other species. We examined the efficacy of MPG in a rabbit model of infarction. Rabbit hearts were subjected to a 30-min coronary artery occlusion. Infarct size expressed as a percentage of risk zone was determined by either triphenyltetrazolium chloride (TTC) staining after 3 h of reperfusion (study 1) or by histology after 72 h of reperfusion (study 2). In study 1, 37 ± 2.6 % of the risk zone infarcted in the control group. Intravenous MPG at a rate of 100 mg/kg/h starting 15 min after the onset of ischemia and continuing until 1 h after reperfusion had no effect on infarct size (35.4 ± 3.4 % infarction). However, infusion of MPG until the end of reperfusion significantly reduced infarct size as measured with TTC to 17.2 ± 2.5 % (p 〈 0.01 vs. control group). In study 2, 48.6 ± 4.0 % of the risk zone infarcted in the control group. In the treatment group MPG was started as above and was continued for 4 h of reperfusion followed by an intramuscular injection at the termination of the intravenous infusion. No protection was seen after 72 h of reperfusion (43.8 ± 2.1 % infarction). These findings reveal that MPG at a dose and schedule that appeared to protect the dog heart could not effect sustained protection in the rabbit heart. TTC staining revealed that MPG appeared to have preserved viability for up to 3 h of reperfusion suggesting that failure may have been due to early withdrawal of the drug. Alternatively, early TTC staining may yield spurious results under conditions in which protection is dependent upon antioxidant or free radical scavenger treatment as has previously been suggested. It is concluded that MPG as administered in the previous canine studies does not limit infarct size in all species, thus raising a concern about MPG's potential efficacy in man.
    Type of Medium: Electronic Resource
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