Norton E D, Jackson E K, Virmani R, Forman M B
Department of Medicine, Vanderbilt University School of Medicine, Nashville, TN.
Am Heart J. 1991 Nov;122(5):1283-91. doi: 10.1016/0002-8703(91)90567-2.
The purpose of this study was to investigate the effects of various doses of adenosine administered intravenously on myocardial reperfusion injury in a model with poor collateral blood flow. New Zealand White rabbits were subjected to 30 minutes of occlusion of the obtuse marginal branch of the left circumflex artery and to 48 hours of reperfusion. Animals were randomized to receive intravenous adenosine in doses of 0.1 mg/min (low), 0.3 mg/min (intermediate), or 0.55 mg/min (high), or an equivalent volume of saline (control) commencing 5 minutes prior to reperfusion and continuing through the first 60 minutes of reperfusion. The area at risk was determined in vivo with Monastral blue dye and the area of necrosis was histologically examined with Masson's trichrome stain. Both the intermediate and high doses of adenosine, but not the low dose, significantly (p less than 0.05) decreased mean blood pressure. However, all three doses of adenosine produced a significant (p less than 0.05) and comparable decrease in infarct size expressed as a percent of area at risk (control, 52.0 +/- 4.6%; low, 35.3 +/- 4.1%; intermediate, 31.7 +/- 4.6%; high, 31.3 +/- 4.6%). Regional myocardial blood flow was significantly increased and coronary vascular resistance decreased by all three doses of adenosine in a subset of animals that did not undergo coronary occlusion (p less than 0.05). This study demonstrates that intravenous administration of nonhypotensive doses of adenosine given during the early reperfusion period attenuates reperfusion injury in a model with poor collateral blood flow.
本研究的目的是在侧支血流较差的模型中,探讨静脉注射不同剂量腺苷对心肌再灌注损伤的影响。将新西兰白兔的左旋支动脉钝缘支闭塞30分钟,然后再灌注48小时。动物被随机分组,在再灌注前5分钟开始静脉注射剂量为0.1mg/min(低剂量)、0.3mg/min(中等剂量)或0.55mg/min(高剂量)的腺苷,或等量的生理盐水(对照组),并持续至再灌注的前60分钟。用专利蓝染料在体内测定危险区,并用马森三色染色法对坏死区进行组织学检查。中等剂量和高剂量的腺苷可显著降低平均血压(p<0.05),而低剂量则无此作用。然而,所有三种剂量的腺苷均能使梗死面积显著减少(p<0.05),且减少程度相当,梗死面积以危险区面积的百分比表示(对照组为52.0±4.6%;低剂量组为35.3±4.1%;中等剂量组为31.7±4.6%;高剂量组为31.3±4.6%)。在未进行冠状动脉闭塞的部分动物中,所有三种剂量的腺苷均显著增加了局部心肌血流量,并降低了冠状动脉血管阻力(p<0.05)。本研究表明,在早期再灌注期间静脉注射非低血压剂量的腺苷可减轻侧支血流较差模型中的再灌注损伤。