1. Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: beneficial effects of iloprost.
- Author
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Lessiani G, Vazzana N, Cuccurullo C, Di Michele D, Laurora G, Sgrò G, Di Ruscio P, Simeone E, Di Iorio P, Lattanzio S, Liani R, Ferrante E, and Davì G
- Subjects
- Aged, Aged, 80 and over, Biomarkers blood, Biomarkers urine, Blood Platelets immunology, CD40 Ligand blood, Chi-Square Distribution, Critical Illness, Dinoprost analogs & derivatives, Dinoprost urine, Drug Administration Schedule, Female, Humans, Iloprost administration & dosage, Infusions, Intravenous, Ischemia blood, Ischemia immunology, Ischemia urine, Italy, Lipid Peroxidation drug effects, Male, Middle Aged, Nitric Oxide blood, Platelet Aggregation Inhibitors administration & dosage, Thromboxane B2 analogs & derivatives, Thromboxane B2 urine, Time Factors, Treatment Outcome, Aspirin therapeutic use, Blood Platelets drug effects, Iloprost therapeutic use, Inflammation Mediators blood, Ischemia drug therapy, Oxidative Stress drug effects, Platelet Activation drug effects, Platelet Aggregation Inhibitors therapeutic use
- Abstract
Platelets critically contribute to atherothrombosis and worsening ischaemia in patients with peripheral arterial disease (PAD), eventually leading to critical limb ischaemia (CLI). Furthermore, persistent platelet activation despite antiplatelet therapy has been reported in this setting. The prostacyclin analogue iloprost is currently recommended in CLI patients for its effects in relieving symptoms by promoting local perfusion. In this study, we investigated the effects of iloprost infusion on urinary 11-dehydro-TXB₂ and 8-iso-PGF(₂α) excretion rate, as in vivo indexes of thromboxane-dependent platelet activation and lipid peroxidation, respectively, and on platelet-derived proinflammatory sCD40L and nitric oxide bioavailability in 44 patients with CLI while on chronic treatment with low-dose aspirin. Daily iloprost infusion for one-week significantly decreased urinary 11-dehydro-TXB₂ [499 (277-807) vs. 380 (189-560) pg/mg creatinine, p < 0.0001] and 8-iso-PGF(₂α) [533 (316-842) vs. 334 (196-540) pg/mg creatinine, p < 0.0001] as well as plasma sCD40L [1540 (1005-3015) vs. 948 (845-2030) pg/ml, p < 0.0001]. Furthermore, a significant increase in plasma nitrate plus nitrite levels has been observed [26.8 (18.8-35.9) vs. 43.7 (33.0-75.5) μM, p < 0.0001]. A significant direct correlation was also found between urinary 8-iso-PGF(₂α) and 11-dehydro-TXB2 before and after iloprost treatment (Rho = 0.695, p < 0.0001). In conclusion, we report that a short-term course of iloprost is able to significantly reduce residual thromboxane biosynthesis, oxidative stress, endothelial dysfunction and platelet-derived inflammation in low-dose aspirin treated patients with CLI.
- Published
- 2011
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