glucuronyl-glucosamine-glycan-sulfate and Arterial-Occlusive-Diseases

Arteries, veins and capillaries share the feature of hosting the "endothelial organ", an ubiquitous structure lining the surface of the entire circulatory tree. Endothelial cells and their supporting elements as the basement membrane, the intracellular matrix, and the surface covering glycocalyx, although displaying significant regional differences, maintain a common response to injury and to pharmacological stimuli. Sulodexide (SDX), a highly purified extractive glycosaminoglycan (GAG), shows many biological actions indicating effectiveness in arterial disorders and diseases. In fact, SDX besides inhibiting experimental arterial thrombogenesis displays, especially by the oral route, a number of vascular protective actions that are largely independent of those affecting blood coagulation. Among the activities relevant to arterial disorders, the agent provides restoration of damaged glycocalyx and of degraded intracellular matrix, as well as antiproliferative, antinflammatory, antioxidant, anti-proteolytic and anti-ischemic activities. Among the latter properties, the inhibiting effect on the enzyme family of matrix metalloproteinases (MMPs), and especially on the expression of MMP9 and its precursor, seems of crucial importance given the role of these matrix degrading enzymes in the pathogenesis and progression of atherothrombosis in coronary, carotid and peripheral arteries. These important biological data, many of them very recent, supply clues for the interpretation of a number of previous clinical trials in arterial diseases. Studies published in the years 1990-2005, showing significant reduction of cardiovascular events after a myocardial infarction, as well as a marked improvement in the walking ability in patients with peripheral arterial disease, deserve today an active re-appraisal likely conducive to new clinical research protocols in the field of primary and secondary prevention of cardiovascular disease of atherothrombotic nature.

Topics: Animals; Arterial Occlusive Diseases; Arteries; Fibrinolytic Agents; Glycosaminoglycans; Humans; Thrombosis; Treatment Outcome

The peripheral obstructive artery disease (POAD) epidemiology raises some concerns about its continuously increased incidence in Western countries. The most part of the patients affected by POAD have systemic cardiovascular complications and die because of cardiac and cerebrovascular disorders. Thus the social cost of this disease is very high. A large part of risk factors for the POAD is well-known and they are reversible trough an efficacious life-style improvement (mainly physical activity increase and cigarette smoking habit cessation) and cardiovascular disease risk factors control (diabetes mellitus, hypercholesterolemia, blood hypertension). On the contrary, no much data are available as it regards efficacious therapies for clinically active disease. The only ones that have been adequately investigated and already available in the market are cilostazol (maybe useful only in more serious patients), and sulodexide (that could improve the pain free walking distance till the 75%). Further research is needed in order to develop new efficacious drugs for POAD treatment, but in the meantime it is necessary to recognise all POAD patients as soon as possible and to treat them adequately with the available therapies.

Topics: Arterial Occlusive Diseases; Cilostazol; Drug Therapy, Combination; Europe; Glycosaminoglycans; Humans; Hypolipidemic Agents; Incidence; Intermittent Claudication; Italy; Lower Extremity; Motor Activity; Smoking Cessation; Tetrazoles; Vasodilator Agents

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 this investigation was to compare the preventive effect of sulodexide, a glycosaminoglycan drug, tested versus ASA-dipyridamole association, on the occlusion of venous aortocoronary bypass. A group A of 23 patients, for a total of 22 anastomosis with internal mammary artery and 46 venous bypass, was treated with sulodexide 500 USL/day. A group B of 18 patients for a total of 19 anastomosis with internal mammary artery and 33 venous bypass, was treated with ASA-dipyridamole 300 mg + 400 mg/day. Three and 9 months after surgery, all patients underwent thallium-201 myocardial perfusion imaging, associated with ergometric test. At the first control after 3 months, reversible perfusion defect in one or more myocardial segments was observed in 8 patients of group A and 3 patients of group B (2 A patients and 1 B patient in non revascularized myocardial segments); after 9 months, reversible perfusion defects were observed in 4 A patients and in 4 B patients. After 3 months, non reversible perfusion defect imaging in non infarcted myocardial segments was observed in 2 A patients and in 1 B patient; after 9 months, in 1 patient of both groups. This research shows higher incidence, at first control after 3 months, of ischemic reversible perfusion defects in patients treated with sulodexide, with an evident improvement in some patients recontrolled after 9 months. At the last control after 9 months, the scintigraphic findings showed similar evidence of perfusion defects in both groups treated with sulodexide or ASA-dipyridamole, with concordant angiographic findings (78.6%). Our preliminary results are encouraging and suggest further widespread studies on sulodexide therapy.

Topics: Arterial Occlusive Diseases; Coronary Angiography; Coronary Artery Bypass; Dipyridamole; Drug Evaluation; Female; Glycosaminoglycans; Humans; Hypolipidemic Agents; Male; Myocardial Reperfusion; Myocardial Revascularization; Postoperative Complications; Thallium Radioisotopes; Vasodilator Agents