We-P11:270 Clinical and immunological effects of one-week treatment with intravenous iloprost in critical limb ischemia patients

Meini, Simone; Pieragalli, D.; Renzo, M. Di; Franco, V. De; Pasqui, Anna Laura; Auteri, A

doi:10.1016/s1567-5688(06)81623-5

Cited by 8 publications

(12 citation statements)

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“…Erythrocyte-derived ATP has been shown to produce vasodilation in isolated lungs (47,49) and isolated arterioles (5,8). Iloprost is used clinically in the treatment of pulmonary hypertension and peripheral vascular disease because of its vasodilator properties (14,23). The PDE3 inhibitor cilostazol is also used in the treatment of peripheral vascular disease (19).…”

Section: Discussionmentioning

confidence: 99%

Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP

Hanson¹,

Stephenson²,

Bowles³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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Increases in the second messenger cAMP are associated with receptor-mediated ATP release from erythrocytes. In other signaling pathways, cAMP-specific phosphodiesterases (PDEs) hydrolyze this second messenger and thereby limit its biological actions. Although rabbit and human erythrocytes possess adenylyl cyclase and synthesize cAMP, their PDE activity is poorly characterized. It was reported previously that the prostacyclin analog iloprost stimulated receptor-mediated increases in cAMP in rabbit and human erythrocytes. However, the PDEs that hydrolyze erythrocyte cAMP synthesized in response to iloprost were not identified. PDE3 inhibitors were reported to augment increases in cAMP stimulated by prostacyclin analogs in platelets and pulmonary artery smooth muscle cells. Additionally, PDE3 activity was identified in embryonic avian erythrocytes, but the presence of this PDE in mammalian erythrocytes has not been investigated. Here, using Western blot analysis, we determined that PDE3B is a component of rabbit and human erythrocyte membranes. In addition, we report that the preincubation of rabbit and human erythrocytes with the PDE3 inhibitors milrinone and cilostazol potentiates iloprost-induced increases in cAMP. In addition, cilostamide, the parent compound of cilostazol, potentiated iloprost-induced increases in cAMP in human erythrocytes. These findings demonstrate that PDE3B is present in rabbit and human erythrocytes and are consistent with the hypothesis that PDE3 activity regulates cAMP levels associated with a signaling pathway activated by iloprost in these cells.

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Section: Discussionmentioning

confidence: 99%

Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP

Hanson¹,

Stephenson²,

Bowles³

et al. 2008

American Journal of Physiology-Heart and Circulatory Physiology

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“…Previous studies suggest some persistence of beneficial effects of even short-term iloprost treatment in terms of transcutaneous oxygen pressure (56), ankle/brachial pressure index and treadmill exercise test (14). However, our data obtained with a one-week iloprost infusion cannot be necessarily extrapolated to longer-term follow-up since the pharmacological benefits of iloprost may fade away with time after discontinuation or induce tachyphylaxis.…”

Section: What Does This Paper Add?mentioning

confidence: 55%

“…Ongoing research with new strategies for angiogenesis and the use of progenitor cells has yielded encouraging results for patients with CLI and limited options (13). Parenteral administration of prostaglandin (PG) E1 or iloprost, a synthetic analogue of prostacyclin, for 7-28 days reduces ischaemic pain and facilitate ulcer healing in patients with CLI, but its efficacy is limited to a small percentage of patients (3,4,14,15).…”

Section: Introductionmentioning

confidence: 99%

Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: Beneficial effects of iloprost

Lessiani¹,

Vazzana²,

Cuccurullo³

et al. 2011

Thromb Haemost

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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.

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“…7 In addition, Meini et al. 8 suggested that clinical improvement with 1 week infusion of iloprost persisted up to 6 months. In our patients, only two patients could not tolerate the regimen, and side effects of short duration did not require the cessation of the treatment in the remaining patients.…”

Section: Discussionmentioning

confidence: 99%

Intravenous iloprost for treatment of critical limb ischemia in patients unsuitable for revascularization

et al. 2014

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We-P11:270 Clinical and immunological effects of one-week treatment with intravenous iloprost in critical limb ischemia patients

Cited by 8 publications

References 0 publications

Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP

Phosphodiesterase 3 is present in rabbit and human erythrocytes and its inhibition potentiates iloprost-induced increases in cAMP

Inflammation, oxidative stress and platelet activation in aspirin-treated critical limb ischaemia: Beneficial effects of iloprost

Intravenous iloprost for treatment of critical limb ischemia in patients unsuitable for revascularization

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