chondroitin-sulfates and Ischemia

Recommendations for transitioning from therapy with heparin or a low-molecular-weight heparin preparation to therapy with an oral anticoagulant in patients with acute venous or arterial thromboembolism have undergone several changes during the last two decades. Physicians are now comfortable with beginning treatment with an oral anticoagulant once the diagnosis is confirmed, and loading doses are no longer considered to be necessary. Exceptions to early transition may be necessary in patients with an extensive iliofemoral or axillary-subclavian vein thrombosis or pulmonary embolism where thrombolytic agents may be indicated, or in individuals who require surgery or other invasive procedures, or if there are concerns about bleeding. The avoidance of early transition to oral anticoagulants in patients with acute heparin-induced thrombocytopenia also has been advised because of the potential for further thrombotic complications, including venous limb gangrene and warfarin-induced skin necrosis.

Topics: Administration, Oral; Anticoagulants; Arginine; Blood Coagulation; Blood Coagulation Factors; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Gangrene; Heparin; Heparitin Sulfate; Hirudins; Humans; Ischemia; Leg; Necrosis; Pipecolic Acids; Recombinant Proteins; Skin; Sulfonamides; Thrombocytopenia; Thrombosis; Warfarin

Critical limb ischaemia often leads to amputation of the limb and potential mortality. Moreover, there are still significant problems with current therapeutic treatments, according to poor revascularisation of degenerated tissue probably due to modifications within the microenvironment. This study is focused on the changes of structure and bioactivity of glycosaminoglycans (GAGs), especially heparan sulphate (HS) and chondroitin sulphate (CS) in rat Extensor Digitorum Longus (EDL) muscle after ischaemia. Male Wistar rats were subjected to ischaemic-injury by ligation of the neurovascular trunk accompanying EDL-tendon. After 4, 8, 15, 21, 60 and 90 d, the rats were sacrificed and the muscles were collected and submitted to histological, biochemical and gene expression assays. We demonstrated that ischaemia induced modification of expression of enzymes involved in GAG biosynthesis which correlated with significant changes in HS and CS structural features such as size and sulphation pattern. These major structural changes are associated to modifications of GAG abilities to bind growth factors and to modulate cell activity. Moreover, a CS hallmark of injury is maintained as well after the regeneration process. Finally, we showed the relevance of the role of this glycanic matrix remodelling, since a GAG mimetic treatment accelerated muscle repair after ischaemia.

Topics: Animals; Cells, Cultured; Chondroitin Sulfates; Disease Progression; Gene Expression; Glycosaminoglycans; Ischemia; Male; Muscle, Skeletal; Rats, Wistar; Regeneration

Neonatal limb ischaemia (NLI) is a rare but potentially catastrophic condition. Although medical therapy remains as first-line treatment, surgery has an important role when limb-threatening events are present. In this paper we outline the milking technique for open thrombectomy used by the senior author in the treatment of 5 NLI cases. We also present the use of Integra and it's specific benefits in the management of wounds in these challenging situations. Skin grafts over the Integra can be avoided by staged excision of the silicone layer from the margins. We believe this is a novel approach to the use of Integra.

Topics: Biocompatible Materials; Chondroitin Sulfates; Collagen; Humans; Infant, Newborn; Ischemia; Thrombectomy; Thrombosis; Upper Extremity; Wound Closure Techniques

Whole ovine caudal intervertebral discs (IVD) were cultured in sufficient and limited nutrition under simulated-physiologic loading for 7 and 21 days.. To study the effect of limited nutrition on disc cells embedded in their native tissue in short- and midterm whole organ disc culture.. Nutrient-limited induction of disc cell death in vitro has been demonstrated and is believed to be a factor in disc degeneration. Nutrient-limited cell death and its consequences, as it relates to degeneration, have not been investigated in the intact IVD.. Ovine IVDs with endplates were cultured for 7 and 21 days under simulated-physiologic loading, either in media with limited (2 g/L) or sufficient (4.5 g/L) glucose concentration. Cell viability, relative gene expression, newly synthesized chondroitin sulfate content, and matrix metalloproteinase (MMP) activity were measured after culture and compared to fresh tissue.. In sufficient glucose media, cell viability was maintained through 7 days to 21 days of culture. In limited glucose, it dropped significantly to 62% in the anulus fibrosus and to 56% in the nucleus pulposus after 7 days and remained so until 21 days (63% in the anulus fibrosus and 52% in the nucleus pulposus). No significant differences were found between culture conditions for relative gene expression, newly synthesized chondroitin sulfate and inactive and active forms of MMP13 and MMP7.. With this culture system, whole IVD explants could be maintained up to 21 days. Cell viability decreased to 50% to 60% under limited nutrition within days and remained so up to 3 weeks. The surviving cells did not compensate matrix production in this time frame.

Topics: Animals; Cell Death; Cell Survival; Chondrocytes; Chondroitin Sulfates; Compressive Strength; Extracellular Matrix; Fibrocartilage; Gene Expression; Glucose; Intervertebral Disc; Intervertebral Disc Displacement; Ischemia; Matrix Metalloproteinases; Organ Culture Techniques; Sheep, Domestic; Weight-Bearing

Type 2 heparin-induced thrombocytopenia is an uncommon but often fatal complication of heparin, frequently difficult to diagnose after cardiac surgery. In this series, we record the clinical presentation, temporal relationship, and treatment outcome of patients diagnosed with heparin-induced thrombocytopenia postoperatively.. Thirty-three consecutive patients (1.1%) with a diagnosis of heparin-induced thrombocytopenia established by a greater than 50% drop in platelet count with or without a thrombotic event and a positive platelet factor-4 assay were reviewed. We recorded the clinical presentation, the time to presentation, treatment, and outcome (thrombosis, mortality). Univariate analysis was performed on 13 preoperative, operative, and postoperative variables.. The cohort was at increased mortality risk as a result of age (69.4 years), reduced cardiac function (46.8%), nonbypass operations (57.6%), emergency surgery (21.2%), and implantation of three assist devices. The mean time to suspect heparin-induced thrombocytopenia postoperatively was 5.4 days, with 22 cases (66.6%) occurring within 5 days. All patients had previous (within 3 months) exposure to heparin, and 66.6% had ongoing treatment with heparin before surgery. Overall mortality was 33%; thrombotic complications occurred in 15 patients (45.5%), with a mortality of 7 (46.6%) despite immediate cessation of heparin and treatment with a nonheparin analog. Thrombocytopenia without thrombosis occurred in 18 patients (54.5%), but a subgroup of 5 patients with nonthrombotic complications accounted for the 4 (22.2%) deaths.. Heparin-induced thrombocytopenia after cardiac surgery is uncommon but may occur within 5 days of surgery, further complicating diagnosis and treatment. Thrombotic complications result in a high mortality despite treatment with a nonheparin analog, and a subgroup of patients with thrombocytopenia fared poorly.

Topics: Aged; Aged, 80 and over; Anticoagulants; Autoantibodies; Cardiac Surgical Procedures; Chondroitin Sulfates; Cohort Studies; Dermatan Sulfate; Diabetes Complications; Female; Gangrene; Heparin; Heparitin Sulfate; Hospital Mortality; Humans; Ischemia; Male; Middle Aged; Platelet Factor 4; Postoperative Complications; Postoperative Period; Retrospective Studies; Risk Factors; Thrombocytopenia; Thrombosis; Time Factors; Treatment Outcome

An 80-year-old woman had been hospitalized in a psychiatric clinic where, on the 22nd day, she sustained a fracture of the neck of the left femur, which was treated by internal screw fixation. The postoperative course was at first without complication. But 9 days postoperatively her platelet count had fallen to 59,000/microliter. As heparin induced type II thrombocytopenia (HIT II) was suspected, the thrombosis prophylaxis with low-molecular heparin was replaced by sodium danaparoid (twice 750 units subcutaneously). Despite this, ischaemia of the right lower leg developed and required amputation. On the following day the left lower leg and foot also became ischemic, where upon she was admitted to the author's hospital (37 days after her admission to the psychiatric clinic).. The patient was in a reduced general condition (body-mass index 19.5 kg/m2). She was disoriented as to place and time. Her blood pressure was 140/80 mmHg, her pulse irregular with a ventricular rate of 100/min. The skin below the middle of the left lower leg was cold and livid and the pedal pulses were not palpable.. Haemoglobin content was 9.7 g/dl, the white cell count 9,200/microliter, and platelet count 54,000/microliter. Electrolytes and creatinine were within normal limits.. Thrombendarterectomy was performed once via the left groin under danaparoid anticoagulation. There was no re-occlusion and the patient was able to walk again.--It was ascertained subsequently, she had already been given ordinary heparin in the psychiatric clinic for 20 days. Her platelet count of around 70,000/microliter returned to normal even though heparin administration was continued.. A reduction in platelet count by more than half during heparin treatment suggests heparin-induced thrombocytopenia, in which case heparin should be discontinued at once. In high-risk patients adequate treatment should be initiated with other anticoagulants even before the occurrence of thromboembolism.

Topics: Aged; Aged, 80 and over; Amputation, Surgical; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Endarterectomy; Female; Heparin; Heparinoids; Heparitin Sulfate; Humans; Ischemia; Leg; Recurrence; Thrombocytopenia; Thromboembolism; Thrombosis

Although standard heparin has been demonstrated to reduce endothelial cell dysfunction in acute ischemia-reperfusion injury, its mechanism of action remains unknown. We hypothesized that heparin's salutary endothelial effects are independent of its conventional anticoagulant activity and are not caused by nonspecific polyanion effects.. Isolated rat hindlimbs were perfused at constant pressure with an albumin-enriched crystalloid buffer. After 60 minutes of normothermic ischemia, endothelial function was assessed by measurement of endothelial-dependent vasodilation by log increment infusion of acetylcholine. Endothelial-independent vasodilation was measured by exposure to nitroprusside. Some groups were pretreated with heparinoids possessing minimal or intermediate anticoagulant activity.. Treatment with heparinoids with low anticoagulant activity significantly increased endothelial-dependent vasodilation when compared with the nontreated ischemic group and were statistically indistinguishable from the nonischemic control. Treatment with dextran sulfate, a randomly sulfated polymer with size and charge characteristics similar to heparin, did not change postischemic vasodilation. Endothelial-independent vasodilation was largely unaffected by ischemia-reperfusion or drug treatment.. A heparinoid with negligible antithrombin-binding activity (Astenose) attenuated postischemic endothelial dysfunction, suggesting that its mechanism of action was independent of anticoagulant activity. Failure of dextran sulfate to be protective implied that the effect was not caused by nonspecific polyanion action.

Topics: Acute Disease; Animals; Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Dextran Sulfate; Endothelium, Vascular; Heparin; Heparitin Sulfate; Hindlimb; In Vitro Techniques; Ischemia; Male; Rats; Rats, Sprague-Dawley; Reperfusion Injury; Vasodilation

Heparin (2,000 U/kg, i.v.) increases the plasma superoxide dismutase (SOD) activity by 2-3 times after 5 min. followed by a gradual decrease. A high dose of heparin (4 x 10(3) and 10 x 10(3) U/kg) exhibits a lower increase in the release of SOD. Ischaemic paw oedema in mice was suppressed by various types of SOD and heparin also suppresses this oedema. The dose-dependent curve of heparin of oedema suppression corresponds well with the increased plasma level of SOD. Inducibility with heparin, slow clearance from the bloodstream and blocking of oedema suppression by the copper chelator, diethyldithiocarbamate (DDC), suggest that the oedema suppressing SOD was the extracellular (EC)-SOD C. Other anticoagulants such as citrate and EDTA had no effect. Chondroitin sulphate A and C or carrageenan exhibited weak suppression. A complex of EC-SOD C and heparin appears not to bind to the endothelium in contrast to the injected free EC-SOD C. When heparin is re-injected, more than 1 week was required to get the same degree of oedema suppression. This indicates the necessity of newly synthesized enzyme. A biological role for heparin-induced release of plasma SOD is demonstrated for the first time in this investigation.

Topics: Animals; Carrageenan; Chondroitin Sulfates; Citrates; Citric Acid; Ditiocarb; Edema; Edetic Acid; Heparin; Hindlimb; Ischemia; Kinetics; Male; Mice; Superoxide Dismutase