leukotriene-e4 and Ischemia

Treatment of severe peripheral arterial occlusive disease requires percutaneous revascularization. However, little is known about risk factors or predictors for reocclusion/restenosis. Cysteinyl leukotrienes are highly bioactive lipid mediators of inflammation. Their intravascular production may take place in the atheromatous plaque or result from interaction within activated leukocyte-platelet aggregates.. We prospectively measured urinary leukotriene E4, the main end-metabolite of cysteinyl leukotrienes in a group of 179 subjects with peripheral artery occlusive disease of the lower extremities. At the enrollment to the study, 22.9% had angioplasty and the remaining had angioplasty with stent implantation. During 12-month follow-up, 29.6% developed reocclusion/restenosis despite a standard pharmacotherapy. We evaluated treatment outcomes at 1, 3, 6 and 12-month follow-up visits, along with urinary leukotriene E4 excretion.. During the study period, we observed a linear increase of urinary leukotriene E4 excretion only in subjects whose lower limb ischemia worsened. Moreover, elevated leukotriene E4 in urine was found only in subjects who developed reocclusion/restenosis. This was significant not only as a coincidence at the time of the follow-up visit, but leukotriene E4 elevation preceded clinical manifestation of reocclusion/restenosis.. Our results demonstrated that serial measurements of urinary leukotriene E4 allowed to predict failure of angioplasty with/or without stent implantation for peripheral artery occlusive disease. However, to prove causality between cysteinyl leukotrienes overproduction and occlusive lower limb ischemia, a clinical trial with leukotrienes modifying drugs would be required.

Topics: Aged; Angioplasty; Arterial Occlusive Diseases; Biomarkers; Coronary Restenosis; Cysteine; Female; Follow-Up Studies; Humans; Ischemia; Leukotriene E4; Leukotrienes; Male; Middle Aged; Peripheral Arterial Disease; Prospective Studies; Time Factors

Baseline level of the cysteinyl leukotriene (CysLT), leukotriene E4 (LTE4), is associated with an increased pain rate in children and adults with sickle cell disease (SCD). To provide additional evidence for a role of CysLTs in the pathogenesis of vaso-occlusion, we tested the hypothesis that LTE4 levels will increase within an individual during painful episodes compared to baseline. In a cohort of 19 children and adults with SCD, median LTE4 levels increased from 82.36 pg/mg creatinine at baseline to 162.81 pg/mg creatinine during a painful episode (P < 0.001). These data further support a contribution of CysLTs to the process of vaso-occlusion.

Topics: Acetates; Adolescent; Adult; Anemia, Sickle Cell; Anti-Asthmatic Agents; Asthma; beta-Thalassemia; Biomarkers; Child; Cohort Studies; Cyclopropanes; Female; Fetal Hemoglobin; Hemoglobin C Disease; Heterozygote; Hospitalization; Humans; Ischemia; Leukotriene Antagonists; Leukotriene E4; Male; Pain; Quinolines; Retrospective Studies; Sickle Cell Trait; Sulfides; Young Adult

It has previously been shown that leukotriene E4 production is increased both in acute and chronic lower limb ischaemia. The aim of this study was to measure the effect of revascularisation on leuktriene E4 excretion in chronic lower limb ischaemia. Revascularisation did not affect significantly on leukotriene E4 excretion (preop. 34.9+/-7.1 pg/mg creatinine, postop. 24.5+/-4.7 pg/mg creatinine, n=10, P<0.238). We suggest that the enhanced leukotriene E4 production continues after revascularisation which may have a therapeutical implication.

Topics: Aged; Chronic Disease; Female; Humans; Ischemia; Leg; Leukotriene E4; Male; Middle Aged; Muscle, Skeletal; Vascular Surgical Procedures