Amelioration of ischemia/reperfusion-induced myocardial infarction by the 2-alkynyladenosine derivative 2-octynyladenosine (YT-146).
The present study was aimed at determining whether the novel adenosine A2-agonist YT-146 may have cardioprotective effects against ischemia-reperfusion injury. Anesthetized open-chest dogs underwent 90-min occlusion of the left anterior descending artery and subsequent 300-min reperfusion. The animals were randomly assigned to receive vehicle, 3, or 10 microg/kg YT-146 or ischemic preconditioning (4 episodes of 5 min occlusion followed by 5 min of reperfusion). Blood pressure, heart rate, and regional myocardial blood flow throughout the experiment were measured, as was the myocardial infarct size after reperfusion. The infarct size of the vehicle-treated dog was 56.2% +/- 2.7% (n = 5), whereas that of 3 or 10 microg/kg YT-146-treated dog was smaller (ie, 29.5% +/- 8.7% or 20.2% +/- 7.0%, respectively; n = 5). The infarct size of the dog treated with 10 microg/kg YT-146 was reduced to a degree similar to that of the ischemic preconditioning (19.2% +/- 6.3%, n = 5). YT-146 at both doses elicited a dose-dependent increase in acute hyperemic coronary flow immediately after reperfusion. The cardioprotective effect may be attributed to the limitation of the infarct size, probably via A2-receptor-mediated coronary artery dilatation during the early period of reperfusion.
Sasamori
Jun
J
Drug Research Department, Fukushima Research Laboratories, Toa Eiyo Ltd., Iizaka, Japan. sasamori.jun@toaeiyo.co.jp
Aihara
Kazuyuki
K
Yoneyama
Fumiya
F
Sato
Isamu
I
Kogi
Kentaro
K
Takeo
Satoshi
S