BN-063, a newly synthesized adenosine A1 receptor agonist, attenuates myocardial reperfusion injury in rats.
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.
Lee
Y M
YM
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Sheu
J R
JR
Yen
M H
MH
D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology*; D001145:Arrhythmias, Cardiac / Q000503:physiopathology / Q000517:prevention & control; D003331:Coronary Vessels / Q000502:physiology; D005260:Female; D006151:Guanosine / Q000031:analogs & derivatives* / Q000494:pharmacology; D006439:Hemodynamics / Q000187:drug effects / Q000502:physiology; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology / Q000517:prevention & control; D015428:Myocardial Reperfusion Injury / Q000188:drug therapy* / Q000503:physiopathology; D058906:Purinergic P1 Receptor Agonists; D051381:Rats; D017207:Rats, Sprague-Dawley
D000889:Anti-Arrhythmia Agents; D058906:Purinergic P1 Receptor Agonists; D006151:Guanosine; C090504:1-cyclopropylisoguanosine