To assess the efficacy of the newly synthesized selective
adenosine A1 receptor agonist,
BN-063 (1-cyclopropylisoguanosine), against
myocardial reperfusion injury, 31 rats underwent 45 min of left coronary artery occlusion and 1 h of reperfusion. Animals were randomly assigned to four groups: control, I0.5-R0.5, in which
BN-063 (0.5 mg/kg i.v. bolus) was administered during both
ischemia and reperfusion, R-0.5 and R-1.0, in which
BN-063 was administered only during reperfusion at 0.5 and 1.0 mg/kg, respectively. The area at risk was determined by intravascular injection of blue
dye during coronary artery occlusion, which was performed by retightening the
ligature at the end of reperfusion, and
infarct size was determined by incubation of heart slices in nitro blue tetrazolium
chloride. A significant reduction in
infarct size, as a percentage of the area at risk, was noted with all three
BN-063 treatment groups (control: 63.5 +/- 4.0%, I0.5-R0.5: 39.6 +/- 3.7%, R-0.5: 37.5 +/- 3.5%, R-1.0: 38.1 +/- 5.2%). However, the I0.5-R0.5 group did not shown a more beneficial effect than the other two BN-063-treated groups. In addition,
BN-063 exerted a protective effect on the number of ventricular premature contractions associated with reperfusion (control: 906 +/- 52, I0.5-R0.5: 325 +/- 61, R-0.5: 321 +/- 95, R-1.0: 340 +/- 46). The results of this study demonstrate that
BN-063, through activation of
adenosine A1 receptors, exerts antiarrhythmic and anti-
infarct effects during
myocardial ischemia-reperfusion. Therefore,
BN-063 would be useful clinically in the treatment and prevention of acute
myocardial infarction.