11-dehydro thromboxane B2 levels after percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease during a one year follow-up period.

The aim of our study was to determine if the generation of thromboxane is altered in patients with peripheral arterial occlusive disease following percutaneous transluminal angioplasty (PTA) during a one year follow-up period. In this study, 175 patients diagnosed with peripheral arterial occlusive disease (PAOD) and demonstrating short-distance claudication or ischemic rest pain, requiring PTA in either the iliac, femoral, or popliteal arteries, were enrolled. The excretion of 11-dehydro thromboxane B2 (TXB2) was measured in urine samples by high-performance liquid chromatography-mass spectrometry and recalculated based on the creatinine concentration. The urine samples were collected the morning prior to PTA, immediately following PTA and the day after PTA. All of the study subjects were then observed for a period of 12 months. Urine samples were also collected during the follow-up visits, and the levels of 11-dehydro TXB2 were measured at 1 month (1458.1 pg/mg creatinine ± 1240.8), 3 months (1623.3 pg/mg creatinine ± 1362.2), 6 months (1314.8 pg/mg creatinine ± 1378.7) and 12 months (1473.2 pg/mg creatinine ± 1455.2) after the PTA procedure. All of the patients were taking 75 mg of aspirin per day throughout the course of the study, as well as 75 mg of clopidogrel for six weeks following PTA. Overall, the mean TXB2 values immediately after PTA were significantly higher than either before the procedure (1524.4 pg/mg creatinine ± 1411.1 vs. 2098.1 pg/mg creatinine ± 1661.8; P = 0.00002), the day after PTA, or at any other point during the study. Moreover, preoperative TXB2 levels correlated well with the composite endpoints of death, myocardial infarction and stroke during the follow-up period (OR 7.42 [CI 95% = 1.2-48.8]; P = 0.02). Our findings suggest that clinicians should consider the use of TXA2 synthase inhibitors and receptor antagonists in combination with peripheral percutaneous transluminal angioplasty in patients with peripheral arterial occlusive disease.

Urinary cysteinyl leukotrienes in one-year follow-up of percutaneous transluminal angioplasty for peripheral arterial occlusive disease.

BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.