glucuronyl-glucosamine-glycan-sulfate and Peripheral-Vascular-Diseases

During arterial hypertension it is often possible to find other factors like lipoidoproteinosis and peripheral arterial disease (POAD), which can accentuate blood rheological abnormalities in hypertensive subjects. A group of hypertensives with lipoidoproteinosis (LP) and POAD were therefore examined to evaluate the relationship between these factors and blood rheological disorders and, if possible, to correct it.. We studied a group of 27 hypertensives with LP and POAD (15 males and 12 females in menopause for at least 1 year, aged 48 +/- 4 years), with WHO stage I hypertension, obesity (BMI = 30 +/- 2), stage II type "a" POAD, class 2 type "b" lipoidoproteinosis (acc. to Fredrick-son's classification) and hyperfibrinogenemia. All patients received oral medication with 500 lipidic units (ULS) sulodexide a day, 20 mg pravastatin o.d. orally, and were put on a low-salt and low-calorie diet (1400 kcal/day) during a follow-up of 60 days. Blood rheology status was evaluated before and after treatment (red blood cell--RBC--deformability and aggregability) using a new computerized instrument, which uses laser rays: the laser assisted optical rotational red cell analyzer (LORCA) (acc. to Hardeman) and RBC deformability using optical microscopy under immersion (acc. to Zipursky and Forconi). Transcutaneous oxymetry was also used to evaluate tissue oxygenation.. At the end of the study a significant improvement (p < 0.01) was noted in the blood rheological patterns of peripheral perfusion and tissue oxygenation. This underlined the positive influence of sulodexide with pravastatin in improving hemorheological patterns and modulating hypercholesterolemia and hyperfibrogenemia in hypertensives with POAD II "a" and LP 2 "b" and blood rheology disorders.

Topics: Adult; Aged; Blood Gas Monitoring, Transcutaneous; Female; Glycosaminoglycans; Hemorheology; Humans; Hypercholesterolemia; Hyperlipidemias; Hypertension; Hypolipidemic Agents; Laser-Doppler Flowmetry; Lasers; Lipoid Proteinosis of Urbach and Wiethe; Male; Middle Aged; Peripheral Vascular Diseases; Pravastatin

Sulodexide is a mixture of heparin and dermatan sulphate which has an antithrombotic action. It was shown that it has also direct effect on the endothelial cells. We tested the effect of sulodexide on the intravascular homeostasis in patients with peripheral vascular disease.. Sulodexide was infused iv. at a dose of 1200 Lipoprotein Lipase Releasing Units (LRU) in 10 patients with peripheral vascular disease. Blood samples were collected before the infusion and 1, 6 and 24 hours after the infusion. Inflammatory and fibrinolytic parameters were studied in the collected serum samples. Additionally, ex-vivo effect of the serum samples on in vitro function of the endothelial cells was studied.. Infusion of sulodexide caused acute and transient peak of the Hepatocyte Growth Factor (HGF) concentration in blood and decrease of the Vascular Endothelial Growth Factor (VEGF) level, what, as we found in in vitro experiments, was due to adsorption of VEGF to endothelium. We found that HGF enhanced in vitro stimulating effect of VEGF on proliferation of the endothelial cells. Serum level of interleukin-6 was gradually decreased, whereas fibrinolytic activity of serum, reflected by t-PA/PAI-1 ratio, increased. Serum samples obtained from the studied patients suppressed oxidative stress and release of interleukin-6 in endothelial cells maintained in in vitro culture.. Sulodexide reduces intravascular inflammation and suppresses inflammatory reaction in the endothelial cells; both effects are desirable in patients with peripheral vascular disease.

Topics: Anticoagulants; Biomarkers; Cell Proliferation; Dose-Response Relationship, Drug; Endothelial Cells; Endothelium, Vascular; Glycosaminoglycans; Hepatocyte Growth Factor; Homeostasis; Human Umbilical Vein Endothelial Cells; Humans; Injections, Intravenous; Middle Aged; Peripheral Vascular Diseases; Vascular Endothelial Growth Factor A; Vasculitis

One hundred and seven adult outpatients with Leriche stage II peripheral occlusive arterial disease took part in this open, controlled trial. Patients were randomly treated over a six-month period either with sulodexide capsules containing 250 lipoproteinlipase releasing units (LRU, two capsules twice daily for 176 days on average: 56 patients), or with pentoxifylline 400 mg tablets (one tablet three times a day for 180 days on average: 51 patients). The incidences of diabetes, hyperlipoproteinaemias, smoking habit and other risk factors were the same in the two groups. The drugs' efficacies were evaluated by monitoring, at the start of treatment and every month during it, the Winsor Index and the walking distance, both prior to (initial claudication distance-IDC) and after (absolute claudication distance-ACD) the symptom's onset. Compliance with treatment and occurrence of adverse events were constantly monitored; systemic tolerability was evaluated through the use of routine haematological and haematochemical tests. Both treatments brought about a progressive increase in the claudication-free walking distance, statistically significant versus baseline from the second month (ACD, sulodexide group) and third month (ACD and ICD, pentoxifilline and sulodexide groups). At the end of treatment, the absolute increase of ACD was significantly greater in sulodexide-treated patients (p < 0.01) with respect to the pentoxifylline-treated group. In both groups the Doppler test evidenced a good improvement in local arterial haemodynamics. In the sulodexide group, 3.6% of patients developed nausea, dyspepsia and other minor gastrointestinal phenomena. In the pentoxifylline group 17.6% of patients complained of gastroenteric disorders (nausea, vomiting, dyspepsia), or of headache and dizziness. In one patient of this latter group insomnia was also present. Systemic tolerance of both drugs was consistently good.

Topics: Administration, Oral; Aged; Arterial Occlusive Diseases; Drug Monitoring; Female; Glycosaminoglycans; Humans; Hypolipidemic Agents; Male; Middle Aged; Pentoxifylline; Peripheral Vascular Diseases; Severity of Illness Index; Ultrasonography; Vasodilator Agents; Walking

The aim of the double-blind, crossover, placebo-controlled study was to evaluate whether oral administration of sulodexide, a medium molecular weight glycosaminoglycan, had an effect on whole blood, plasma and serum viscosity, and/or plasma fibrinogen concentrations. The drug was administered orally at a dose of 500 lipoproteinlipase releasing units twice daily for 1 month to two groups of 20 patients with peripheral vascular disease; one group was administered a placebo--drug sequence and the other a drug--placebo sequence. Orally administered sulodexide had a marked effect on plasma viscosity and on plasma fibrinogen concentrations, whereas there were no effects on whole blood viscosity. No significant side-effects were observed. The fact that sulodexide was highly effective, even after oral administration, suggests it may be useful for the treatment of patients with atheromatous vascular diseases of the lower limbs requiring chronic therapy.

Topics: Administration, Oral; Adult; Blood Coagulation; Blood Viscosity; Double-Blind Method; Female; Fibrinogen; Glycosaminoglycans; Humans; Male; Middle Aged; Peripheral Vascular Diseases; Thrombosis