PROSTACYCLIN PROTECTS ISCHEMIC REPERFUSED MYOCARDIUM IN THE DOG BY INHIBITION OF NEUTROPHIL ACTIVATION
PROSTACYCLIN PROTECTS ISCHEMIC REPERFUSED MYOCARDIUM IN THE DOG BY INHIBITION OF NEUTROPHIL ACTIVATION
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DOI：
10.1016/0002-8703(87)90020-2
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发表时间：
1987-01-01
影响因子：
4.8
通讯作者：
LUCCHESI, BR
中科院分区：
文献类型：
--
作者：
SIMPSON, PJ;MITSOS, SE;LUCCHESI, BR
前列环素（PGI 2）和稳定的PGI 2类似物SC 39902（6，9 α-环氧，5S-氟-11 α，在麻醉开胸犬，结扎左冠状动脉回旋支（LCCA）90分钟，再灌注6小时，观察15 S-去羟基前列腺素-6，13 E-二烯-1-酸钠盐）对PGI 2（50 ng/kg/min，输注至左心房）与对照组相比，梗死面积减少了59%，但SC 39902（1.5 μ g/kg/min）未能显著减少梗塞面积。PGI 2和SC 39902降低平均动脉血压、心率和心率-血压乘积的程度相同。在PGI 2和对照治疗组中，用放射性标记示踪剂微球测量的局部心肌血流量在LCCA闭塞90分钟期间未显示缺血心肌的局部血流量增加。从全血中分离犬中性粒细胞，并用调理剂化的酵母聚糖活化。PGI 2产生浓度依赖性抑制中性粒细胞活化，通过超氧化物产生在体外测定，而SC 39902未能有效地抑制中性粒细胞活化。当狗用PGI 2（50 ng/kg/min，静脉注射）预处理时，神经元迁移到炎性皮肤病变中被有效地减弱。因此，它是建议，在心肌缺血和再灌注期间的细胞保护作用的PGI 2有关的中性粒细胞迁移的抑制和细胞毒性活性氧的产生。
Prostacyclin (PGI2) and the stable PGI2 analogue SC39902 (6,9.alpha.-epoxy,5S-fluoro-11.alpha.,15S-dehydroxyprosta-6,13E-dien-1-oic acid, sodium salt) were studied in anesthetized open-chest dogs subjected to 90 minutes of left circumflex coronary artery (LCCA) occlusion and 6 hours of reperfusion, PGI2 (50 ng/kg/min, infused into the left atrium) reduced infarct mass by 59% compared to control, but SC39902 (1.5 .mu.g/kg/min) failed to produce a significant reduction in infarct size. Both PGI2 and SC39902 reduced mean arterial blood pressure, heart rate, and rate-pressure product to the same extent. Regional myocardial blood flow measured with radiolabeled tracer microspheres did not demonstrate an increase in regional blood flow to the ischemic myocardium during the 90 minutes of LCCA occlusion in the PGI2 and control treatment groups. Canine neutrophils were isolated from whole blood and activated with opsonized zymosan. PGI2 produced a concentration-dependent inhibition of neutrophil activation as measured by superoxide production in vitro, whereas SC39902 failed to effectively inhibit neutrophil activation. Neutrophil migration into inflammatory skin lesions was effectively attentuated when dogs were pretreated with PGI2 (50 ng/kg/min, intravenously). Therefore, it is suggested that the cytoprotective effect of PGI2 during myocardial ischemia and reperfusion is related to an inhibition of neutrophil migration and the production of cytotoxic activated oxygen species.