Lee Y M, Sheu J R, Yen M H
Department of Pharmacology, National Defense Medical Center, Taipei, Taiwan, ROC.
Eur J Pharmacol. 1995 Jun 12;279(2-3):251-6. doi: 10.1016/0014-2999(95)00164-g.
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.
为评估新合成的选择性腺苷A1受体激动剂BN - 063（1 - 环丙基异鸟苷）对心肌再灌注损伤的疗效，31只大鼠经历了45分钟的左冠状动脉闭塞和1小时的再灌注。动物被随机分为四组：对照组、I0.5 - R0.5组（在缺血和再灌注期间均静脉推注0.5mg/kg的BN - 063）、R - 0.5组和R - 1.0组（分别仅在再灌注期间静脉推注0.5mg/kg和1.0mg/kg的BN - 063）。在冠状动脉闭塞期间通过血管内注射蓝色染料来确定危险区域，这在再灌注结束时通过重新收紧结扎线来进行，梗死面积通过将心脏切片在氯化硝基四氮唑蓝中孵育来确定。所有三个BN - 063治疗组梗死面积占危险区域的百分比均显著降低（对照组：63.5±4.0%，I0.5 - R0.5组：39.6±3.7%，R - 0.5组：37.5±3.5%，R - 1.0组：38.1±5.2%）。然而，I0.5 - R0.5组并未显示出比其他两个BN - 063治疗组更有益的效果。此外，BN - 063对与再灌注相关的室性早搏数量具有保护作用（对照组：906±52，I0.5 - R0.5组：325±61，R - 0.5组：321±95，R - 1.0组：340±46）。本研究结果表明，BN - 063通过激活腺苷A1受体，在心肌缺血 - 再灌注期间发挥抗心律失常和抗梗死作用。因此，BN - 063在急性心肌梗死的治疗和预防中具有临床应用价值。
