DOES TISSUE-TYPE PLASMINOGEN-ACTIVATOR HAVE DIRECT BENEFICIAL-EFFECTS ON THE MYOCARDIUM INDEPENDENT OF ITS ABILITY TO LYSE INTRACORONARY THROMBI
DOES TISSUE-TYPE PLASMINOGEN-ACTIVATOR HAVE DIRECT BENEFICIAL-EFFECTS ON THE MYOCARDIUM INDEPENDENT OF ITS ABILITY TO LYSE INTRACORONARY THROMBI
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DOI：
10.1161/01.cir.79.5.1125
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发表时间：
1989-05-01
期刊：
影响因子：
37.8
通讯作者：
HALE, S
中科院分区：
文献类型：
--
作者：
KLONER, RA;ALKER, K;HALE, S
组织型纤溶酶原激活剂（t-PA）是一种广泛用于治疗急性心肌梗塞的溶栓剂。之前的一些研究表明，t-PA 对心脏有益，与溶解冠状动脉血栓无关。本研究的目的是确定 t-PA 是否独立于溶解的冠状动脉血栓直接影响梗塞面积、影响无复流现象并加剧心肌内出血。我们使用了左冠状动脉前降支闭塞 2 小时，然后再灌注 4 小时的犬模型。闭塞后 30 分钟施用 t-PA，并持续 2 小时。低剂量研究中盐水组 (28.+-. 8%) 和 t-PA (35.+-. 9%) 组之间以及高剂量研究中盐水组 (46.+-. 12%) 和 t-PA (44.+-. 12%) 组之间心肌梗死面积占风险区的百分比相似。 t-PA 没有改善无回流焊。梗塞内的心肌内血红蛋白水平在盐水(16μg/mg)和高剂量t-PA(12μg/mg)组之间相似。通过心肌内血红蛋白评估的出血程度与梗塞面积相关。组织学评估显示，微观出血仅限于收缩带坏死区域。早期再灌注期间中性粒细胞浸润很明显。总之，t-PA 并没有直接使心肌受益或无复流。它对患者的影响可能是由于其溶解血栓的能力。 t-PA 不会导致出血浸润到非梗塞组织中。再灌注会加速心肌梗塞后的炎症反应，并导致早期强烈的中性粒细胞浸润。
Tissue-type plasminogen activator (t-PA) is a widely used thrombolytic agent for treating acute myocardial infarction. Some previous studies suggest that t-PA benefits the heart independently of lysing coronary artery thrombi. The purpose of this study, was to determine whether t-PA directly affects infarct size independently of lysing coronary thrombi, affects the no-reflow phenomenon, and exacerbates intramyocardial hemorrhage. We used a canine model of 2 hours of occlusion of the left anterior descending coronary artery followed by 4 hours of reperfusion. t-PA was administered 30 minutes after occlusion and was continued for 2 hours. Myocaridal infarct size as a percentage of the risk zone was similar between saline (28 .+-. 8%) and t-PA (35 .+-. 9%) groups in a low-dose study and between saline (46 .+-. 12%) and t-PA (44 .+-. 12%) groups in a high-dose study. t-PA did not improve no-reflow. Intramyocardial hemoglobin level within the infarct was similar between saline (16 .mu.g/mg) and high-dose t-PA (12 .mu.g/mg) groups. The extent of hemorrhage assessed by intramyocardial hemoglobin correlated with infarct size. Histologic evaluation revealed that microscopic hemorrhage was confined to zones of contraction band necrosis. Neutrophil infiltration during early reperfusion was prominent. In conclusion, t-PA did not directly benefit the myocardium or no-reflow. Its effects in patients are likely due to its ability to lyse thrombi. t-PA did not cause infiltration of hemorrhage into noninfarcted tissue. Reperfusion accelerates the inflammatory response after myocardial infarction and results in early, intense neutrophil infiltration.