Mehta J L, Nichols W W, Saldeen T G
Department of Medicine, University of Florida College of Medicine, Gainesville 32610.
J Cardiovasc Pharmacol. 1989 Jun;13(6):803-11. doi: 10.1097/00005344-198906000-00001.
Intracoronary thrombi resulting in acute myocardial ischemia can often be lysed by thrombolytic agents. We examined the potential of a fibrin(ogen)-degradation product pentapeptide 6A (Ala-Arg-Pro-Ala-Lys), which increases coronary blood flow partly by stimulation of prostacyclin release, in reestablishing coronary blood flow in dogs with experimentally induced thrombus. An occlusive thrombus in the circumflex coronary artery was created by electrical stimulation of the endothelial surface. After the occlusive thrombus was stable without electrical current for at least 15 min, peptide 6A (5 mumol/min for 20 min intracoronary) or tissue-plasminogen activator (t-PA) [10 micrograms/kg/min for 20 min intravenously (i.v.)] was randomly administered. Peptide 6A administration reestablished coronary blood flow (peak 16 +/- 2 ml/min, mean +/- SE) in 6 of 12 animals with occlusive coronary thrombus. Mean time to blood flow reestablishment was 5.3 +/- 2.2 min, but the reflow was short lived (mean duration of reflow: 15.7 +/- 1.6 min). t-PA reestablished coronary blood flow (peak 19 +/- 3 ml/min) in 4 of 10 animals. The time of flow reestablishment was 12.0 +/- 3.9 min and the reflow persisted for 22.0 +/- 3.1 min. Peptide 6A administration was associated with an increase in coronary venous plasma 6-keto-PGF1 alpha, indicating stimulation of prostacyclin release. This study demonstrates the potential of peptide 6A in reestablishing coronary blood flow in a canine model of coronary thrombosis. This transient effect is associated with release of prostacyclin, which may be beneficial because of its vasodilator and platelet inhibitory effects.
导致急性心肌缺血的冠状动脉内血栓通常可被溶栓剂溶解。我们研究了一种纤维蛋白（原）降解产物五肽6A（丙氨酸 - 精氨酸 - 脯氨酸 - 丙氨酸 - 赖氨酸）在实验性诱导血栓形成的犬类中重建冠状动脉血流的潜力，该五肽部分通过刺激前列环素释放来增加冠状动脉血流。通过电刺激内皮表面在左旋冠状动脉中形成闭塞性血栓。在闭塞性血栓在无电流情况下稳定至少15分钟后，随机给予肽6A（冠状动脉内5 μmol/分钟，持续20分钟）或组织型纤溶酶原激活剂（t-PA）[静脉内（i.v.）10 μg/（kg·分钟），持续20分钟]。给予肽6A后，12只患有闭塞性冠状动脉血栓的动物中有6只重建了冠状动脉血流（峰值16±2 ml/分钟，平均值±标准误）。血流重建的平均时间为5.3±2.2分钟，但再灌注持续时间较短（再灌注平均持续时间：15.7±1.6分钟）。t-PA使10只动物中的4只重建了冠状动脉血流（峰值19±3 ml/分钟）。血流重建时间为12.0±3.9分钟，再灌注持续22.0±3.1分钟。给予肽6A与冠状动脉静脉血浆中6-酮-PGF1α增加有关，表明刺激了前列环素释放。本研究证明了肽6A在冠状动脉血栓形成犬模型中重建冠状动脉血流的潜力。这种短暂效应与前列环素释放有关，由于其血管舒张和血小板抑制作用，可能是有益的。
