title: Iloprost inhibits neutrophil function in vitro and in vivo and limits experimental infarct size in canine heart.
abstract: 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. Iloprost (0.1-100 microM) inhibited the in vitro production of superoxide anion by canine neutrophils in a concentration-dependent manner. Iloprost (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 C5a in 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 less than 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 less than 0.01. Iloprost 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 less than 0.01.(ABSTRACT TRUNCATED AT 250 WORDS)
mesh_terms: D000818:Animals; D002317:Cardiovascular Agents / Q000494:pharmacology*; D003326:Coronary Circulation / Q000187:drug effects; D004285:Dogs; D011464:Epoprostenol / Q000494:pharmacology*; D006439:Hemodynamics / Q000187:drug effects; D016285:Iloprost; D066298:In Vitro Techniques; D008297:Male; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000378:metabolism; D009504:Neutrophils / Q000187:drug effects* / Q000502:physiology; D010101:Oxygen Consumption / Q000187:drug effects; D009195:Peroxidase / Q000378:metabolism; D013481:Superoxides / Q000097:blood
chemical_list: D002317:Cardiovascular Agents; D013481:Superoxides; D011464:Epoprostenol; D009195:Peroxidase; D016285:Iloprost