Revascularization decreases 8-isoprostaglandin F 2 α excretion in chronic lower limb ischemia

Abstract

8-Isoprostaglandin F 2 α is one of a series of isoprostanes formed by free radical catalysed peroxidation of arachidonic acid. Urinary 8-isoprostaglandin F 2 α is a new marker which reflects oxidative stress in vivo and can be utilized as a diagnostic tool to assess the extent of oxidative stress in various disease states associated with lipid peroxidation. Increased levels of 8-isoprostaglandin F 2 α in cardiac ischemia/reperfusion provide evidence for oxidative stress during coronary perfusion. In animal studies, the restoration of blood flow after lower limb ischemia is followed by reperfusion syndrome. In this study we investigated whether lower limb ischemia/reperfusion is associated with oxidative stress, as reflected by urinary levels of 8-isoprostaglandin F 2 α . Ten patients (mean age 72 years, range 61–82 years) suffering from chronic lower limb ischemia and 10 healthy volunteers (mean age 69 years, range 60–79 years) participated in the study. In all patients, diagnostic angiography had revealed stenosis or occlusion either in the aortoiliac or femoropopliteal region. Surgical revascularization consisted of femoropopliteal reconstruction, femorofemoral reconstruction, aortobifemorial reconstruction, or femoral endartectomy. Urine samples from patients were collected a day before surgery and in the second postoperative day. Urinary 8-isoprostaglandin F 2 α was extracted on a C 2 silica cartridge and determinated by radioimmunoassay. After revascularization, 8-isoprostaglandin F 2 α excretion (pg/μmol creatinine, mean±SD) was decreased by 2.5-fold (preoperative 48.9±8.9, postoperative 19.1±9.5, P<0.001). The postoperative values were similar to the concentrations measured in healthy volunteers (18.0±11.0). All revascularizations were successful, and the increase in ankle-brachial index (preoperative 0–0.6, postoperative 0.4–0.8) revealed improved blood flow in the ischemic lower limb. We suggest that, as assessed by the quantitation of urinary 8-isoprostaglandin F 2 α , chronic lower limb ischemia is associated with increased oxidative stress, which is decreased by revascularization.