heparitin-sulfate and Intermittent-Claudication

Arteriogenesis is an important process for adapting the pre-existing circuit of vessels into functional collateral conduits for delivery of oxygen enriched blood to tissue distal to occlusion of a large, peripheral conduit artery. Recent evidence has shown that arteriogenesis is regulated by nitric oxide (NO), angiogenic factors and shear stress. NO significantly impacts vasomotor tone to enhance conductance of the newly recruited collateral arteries, and this effect is augmented by exercise training prior to arterial occlusion. NO-mediated increases in vascular conductance allows for greater collateral dependent blood flow to the tissue distal to occlusion. NO production is also critical to the efficacy of therapeutic arteriogenesis achieved by delivery of exogenous angiogenic growth factors (VEGF, FGF-2) or by exercise training. The critical role of NO in therapeutic arteriogenesis is independent of NO-mediated changes in vascular conductance and implies a central role in arteriogenic signaling events. Maintenance, or improvement, of NO production and signaling, such as with regular exercise, may improve endothelial cell function and thus may help preserve the arteriogenic potential of preexisting collateral networks.

Topics: Animals; Arteries; Blood Flow Velocity; Cattle; Collateral Circulation; Femoral Artery; Fibroblast Growth Factor 2; Heparin Lyase; Heparitin Sulfate; Humans; Intermittent Claudication; NG-Nitroarginine Methyl Ester; Nitric Oxide; Vascular Endothelial Growth Factor A

Topics: Abciximab; Animals; Anistreplase; Antibodies, Monoclonal; Anticoagulants; Aspirin; Chondroitin Sulfates; Clopidogrel; Dermatan Sulfate; Drug Combinations; Fibrinolytic Agents; Heparin, Low-Molecular-Weight; Heparitin Sulfate; Humans; Immunoglobulin Fab Fragments; Intermittent Claudication; Platelet Aggregation Inhibitors; Streptokinase; Ticlopidine; Vascular Diseases; Venous Thrombosis

Peripheral arterial disease (PAD) is by far the most common cause of intermittent claudication. This disease can greatly reduce the affected individual's walking capacity and can seriously affect daily life activities. Few therapeutic options are aimed at improving walking capacity. This was a randomized, doubleblind, placebo-controlled, multicenter trial, performed in 24 Italian centers. Two hundred seventeen patients with intermittent claudication (stages IIa and IIb of Fontaine's PAD classification) were randomly assigned to heparan sulfate (40 mg orally twice a day) or placebo for 6 months. The primary end-point was an increase in pain-free walking distance [initial claudication distance (ICD)] during the 24 weeks of treatment. The pain-free and the absolute walking distance (ACD) were monitored by standardized treadmill test at baseline and at 4, 12 and 24 weeks. The change in initial claudication distance during treatment, expressed as integrated change over time, was significantly greater with heparan sulfate than with placebo (306 +/- 494 vs. 250 +/- 510 meters x months, p = 0.019). Significantly fewer treated patients worsened during treatment (decreased initial claudication distance) compared with controls (9.1% vs. 19.6%; p = 0.027). Functional recovery in the most severely affected subgroup of patients (stage IIb of Fontaine's classification) was more clearly detected and significantly greater among treated than among control patients (absolute increase in ICD: 70 +/- 113 vs. 58 +/- 172 meters, p = 0.028; integrated increase: 304 +/- 422 vs. 208 +/- 503 meters x months; p = 0.004). Heparan sulfate appeared to increase the walking capacity of patients with intermittent claudication to a significantly greater extent than did placebo. The treatment was well tolerated.

Topics: Aged; Anticoagulants; Double-Blind Method; Female; Hemodynamics; Heparitin Sulfate; Humans; Intermittent Claudication; Male; Middle Aged; Quality of Life; Time Factors; Walking

The aim of this study has been to assess the efficacy and the safety of heparansulphate administered with indobufen in the treatment of occlusive arterial disease.. In a controlled open study, nineteen out-patients with Fontaine's stage II occlusive arterial disease since one year were randomly assigned to treatment with indobufen 200 mg/day or indobufen 200 mg/day and heparansulphate 200 mg/day for 6 months. Efficacy assessments were based on functional evaluations (pain-free sub-maximal exercise ergometric test, ankle-arm pressure ratio at rest and after induced ischemia), on hemocoagulative parameters and on physical signs and subjective symptoms assessed monthly over the whole period of treatment. All patients but one who was lost to follow-up completed the study treatment period as foreseen by the experimental protocol.. The results of the study show an improvement of 10.89% (day 30), 15.92% (day 60), 21.04% (day 90), 24.19% (day 120), 25.18 (day 150) 28.84% (day 180) end of study in ergometric test pain-free interval obtained by patients treated with heparansulphate and indobufen with respect to patients receiving indobufen alone. Also hemocoagulative parameters and signs and patients' subjective symptoms were positively influenced by the association heparansulphate and indobufen.. On the whole, the results of the study indicate that heparansulphate in association with antiplatelet therapy with indobufen has a beneficial effect in the treatment of peripheral occlusive arterial disease.

Topics: Adult; Aged; Arterial Occlusive Diseases; Female; Heparitin Sulfate; Humans; Intermittent Claudication; Isoindoles; Leg; Male; Middle Aged; Phenylbutyrates; Platelet Aggregation Inhibitors

An experimental clinical trial was carried out using heparan sulphate in order to assess its antithrombophilic, profibrinolytic and possibly hemorheological characteristics. Twenty patients with stage 2 obliterating arteriopathy of the lower limbs were enrolled in the study. Patients were fully informed regarding the experimental protocol: a controlled, crossover and double-blind study. The population sample included 20 subjects, male and female, mean age 60.9 years who received heparan sulphate at a dose of 200 mg/die (one 100 mg tablet twice a day): treatment continued for 120 days (60 days of treatment with heparan sulphate and 60 days with placebo). The results obtained were in favour of medical therapy which was significantly more effective than placebo in relation to a number of parameters: compared to basal values, walking parameters were improved, recovery times were more rapid and gait was longer. Significant changes in hemocoagulative and hemorheological parameters were also observed (euglobulin lysis time, fibrin degradation products, erythrocytic filtration, hematic viscosity) and their positive trend may account for peripheral hematic perfusion, as shown by photoplethysmographic tests, velocimetric tests and the modification of the Windsor index. Therapeutic efficacy and the good tolerance (one case of gastralgia, two of pyrosis) as well as broad safety margins offered by the drug justify the use of heparan sulphate in all clinical conditions characterized by thrombophilia and local ischemia, above all those which require long-term treatment.

Topics: Adult; Blood Coagulation; Blood Viscosity; Double-Blind Method; Drug Tolerance; Female; Heparitin Sulfate; Humans; Intermittent Claudication; Male; Time Factors