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)

Polymorphonuclear Leukocyte Behavior in a Nonhuman Primate Focal Ischemia Model

“…In this model collateral blood flow was increased and the frequency of arrhythmias was decreased, suggesting an influence of O2' -on hemodynamics. Simpson et al (1965) administered Iloprost to dogs undergoing myocardial I/R, which significantly re duced infarct size. PMN leukocyte accumulation 6 h after R was markedly reduced based on tissue myeloperoxidase activity.…”

Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism.

“…Neutrophil attachment to vessel walls and emigration into cardiac tissue begins shortly after the initiation of reperfusion (3)(4)(5)(6)(7)(8), and various experimental manipulations in animal models designed to remove neutrophils from the circulation (3,6,(9)(10)(11)(12) or to inhibit their functions (13)(14)(15)(16)(17)(18) have resulted in measurable reductions in the extent of myocardial damage after isch-emia and reperfusion. The mechanisms by which neutrophils effect this tissue damage remain uncertain, though two possibilities have been supported by experimental evidence.…”

Antioxidative effects of adrenomedullin and vascular endothelial growth factor on lung injury induced by skeletal muscle ischemia-reperfusion

“…Several mechanisms have been proposed for the protective effects of AM. It has been shown to possess a number of biological effects in addition to its well-known vasoactive activity (23). These include cell proliferation, differentiation, and oxidative stress-induced cell death inhibition (24)(25)(26).…”