Iloprost Inhibits Neutrophil Function In Vitro and In Vivo and Limits Experimental Infarct Size in Canine Heart
作者:
Paul Simpson,
Judith Mickelson,
Joseph Fantone,
Kim Gallagher,
Benedict Lucchesi,
期刊:
Circulation Research
(OVID Available online 1987)
卷期:
Volume 60,
issue 5
页码: 666-673
ISSN:0009-7330
年代: 1987
出版商: OVID
关键词: myocardial infarction;inflammation neutrophil;myocardial reperfusion;myeloperoxidase;iloprost
数据来源: OVID
摘要:
The prostacyclin analogue iloprost (ZK 36374) inhibits neutrophil activation in vitro, reduces neutrophil accumulation in inflammatory skin lesions, and reduces ultimate infarct size in an anesthetized open-chest canine model of regional ischemia and reperfusion. Doprost (0.1–100 μM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Doprost (100 ng/kg/min i.v.) inhibited C5a-induced neutrophil migration into inflammatory skin lesions as assessed by the neutrophil-specific enzyme marker, myeloperoxidase. The myeloperoxidase activity determined 2 hours after the intradermal administration of C5ain each of the groups was control 13.3 ± 1.8 units/g tissue (n= 12) and iloprost 6.5 ± 0.9 units/g (n= 12),p<0.01. Iloprost was administered to anesthetized open-chest dogs (100 ng/kg/min) 10 minutes after left circumflex coronary artery (LCCA) occlusion and continued during the 90-minute occlusion period and the first 2 hours of reperfusion. Regional myocardial blood flow was similar between treatment groups at baseline, 5 minutes and 80 minutes after LCCA occlusion, and after 1 hour of reperfusion. Infarct size, assessed 6 hours after reperfusion, was reduced by iloprost treatment: 22.4 ± 3.1 % of the area at risk(n= 15) compared with 42.4 ± 3.3% of control (n= 13),p<0.01. Doprost treatment reduced the accumulation of neutrophils (measured by myeloperoxidase activity) in the ischemic myocardium at the Interface between infarcted and noninfarcted tissue: control(n= 9) 9.0 ± 1.8 units/g tissue, iloprost (n= 6) 2.0 ± 0.4 units/g,p<0.01. The ability of iloprost to reduce Infarct size may be related both to a reduction in arterial blood pressure and to a modulation of neutrophil infiltration and activation at the site of tissue injury.
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