heparitin-sulfate and Myocardial-Infarction

Accomplishing a successful percutaneous coronary intervention in a patient with a suspected or diagnosed heparin-induced thrombocytopenia (HIT) requires the selection of an appropriate alternative anticoagulant and a thorough assessment of bleeding and thrombotic risks. In this review, we suggest an evidence-based management algorithm that takes into account the clinical phase of HIT (acute, recent, and remote HIT) and the associated risk when patients present with acute coronary syndrome. The algorithm also integrates preventive measures directed at decreasing the bleeding risk associated with the antithrombotic and invasive therapies used for HIT and percutaneous coronary intervention.

Topics: Algorithms; Angioplasty, Balloon, Coronary; Anticoagulants; Arginine; Chondroitin Sulfates; Comorbidity; Dermatan Sulfate; Drug Therapy, Combination; Fibrinolytic Agents; Fondaparinux; Heparin; Heparinoids; Heparitin Sulfate; Hirudins; Humans; Myocardial Infarction; Peptide Fragments; Pipecolic Acids; Polysaccharides; Recombinant Proteins; Sulfonamides; Syndrome; Thrombocytopenia; Vitamin K

In cardiogenic shock (CS), pathophysiological changes include microcirculatory dysfunction, vascular leakage, and an increase in platelet and leukocyte adhesion to the endothelium, as well as endothelial activation and dysfunction. The endothelial glycocalyx has been recognized as a central modulator of these processes. Glycosaminoglycan heparan sulfate is a major component of the glycocalyx of endothelial cells, and syndecan-1 (S1) represents the most prevalent proteoglycan. The aim of the current study was to investigate circulating levels of the glycocalyx components in patients with infarct-related CS. In 184 patients with CS complicating acute myocardial infarction, blood samples were collected at admission and after one day. Intra-aortic balloon pumping was used in 94 patients (51%). Glycosaminoglycan heparan sulfate and S1 were measured using standard enzyme-linked immunosorbent assay kits. All-cause mortality at 30 days was used for outcome assessment. Levels of S1 decreased between days 1 and 2 (339 [interquartile range [QR], 109-852] vs. 220 [IQR, 57-606] ng/mL; P = 0.01). In contrast, glycosaminoglycan heparan sulfate increased over time (1.9 [IQR, 0.3-6.4] vs. 7.1 [IQR, 3.7-11.7] mg/mL; P < 0.001). Survivors at 30 days had lower admission S1 levels (P < 0.001). In multivariable analysis, S1 remained an independent predictor of 30-day mortality (odds ratio per μg/mL, 2.2 [95% confidence interval, 1.30-3.58]; P = 0.003) together with serum lactate, age, and ejection fraction. Increased levels of S1 are an independent predictor of short-term mortality in patients with acute myocardial infarction and CS.ClinicalTrials.gov Identifier: NCT00491036.

Topics: Aged; Aged, 80 and over; Aorta; Cardiac Catheterization; Female; Glycocalyx; Glycosaminoglycans; Heparitin Sulfate; Humans; Intra-Aortic Balloon Pumping; Male; Microcirculation; Middle Aged; Multivariate Analysis; Myocardial Infarction; Odds Ratio; Prognosis; Proteoglycans; Shock, Cardiogenic; Syndecan-1; Time Factors; Treatment Outcome

Topics: Biological Availability; Extracellular Matrix; Heparitin Sulfate; Humans; Myocardial Infarction; Sulfatases; Vascular Endothelial Growth Factor A

Recent evidence suggests that Toll-like receptor 4 (TLR4) is not only involved in innate immunity but is also an important mediator of adverse left ventricular remodeling and heart failure following acute myocardial infarction (MI). TLR4 is activated by lipopolysaccharide (LPS) but also by products of matrix degradation such as hyaluronic acid and heparan sulfate. Although cardioprotective properties of adenosine (Ado) have been extensively studied, its potential to interfere with TLR4 activation is unknown. We observed that TLR4 pathway is activated in white blood cells from MI patients. TLR4 mRNA expression correlated with troponin T levels (R (2) = 0.75; P = 0.01) but not with levels of white blood cells and C-reactive protein. Ado downregulated TLR4 expression at the surface of human macrophages (-50%, P < 0.05). Tumor necrosis factor-α production induced by the TLR4 ligands LPS, hyaluronic acid, and heparan sulfate was potently inhibited by Ado (-75% for LPS, P < 0.005). This effect was reproduced by the A2A Ado receptor agonist CGS21680 and the non-selective agonist NECA and was inhibited by the A2A antagonist SCH58261 and the A2A/A2B antagonist ZM241,385. In contrast, Ado induced a 3-fold increase of TLR4 mRNA expression (P = 0.008), revealing the existence of a feedback mechanism to compensate for the loss of TLR4 expression at the cell surface. In conclusion, the TLR4 pathway is activated after MI and correlates with infarct severity but not with the extent of inflammation. Reduction of TLR4 expression by Ado may therefore represent an important strategy to limit remodeling post-MI.

Topics: Adenosine; Adenosine A2 Receptor Agonists; Adenosine A2 Receptor Antagonists; Adult; Aged; Case-Control Studies; Cell Membrane; Cells, Cultured; Dose-Response Relationship, Drug; Down-Regulation; Female; Heparitin Sulfate; Humans; Hyaluronic Acid; Inflammation; Ligands; Lipopolysaccharides; Luxembourg; Macrophages; Male; Middle Aged; Myocardial Infarction; Receptor, Adenosine A2A; Receptor, Adenosine A2B; Registries; RNA, Messenger; Time Factors; Toll-Like Receptor 4; Tumor Necrosis Factor-alpha

We examined the vascular expression levels of extracellular superoxide dismutase (EC-SOD), a major antioxidant enzyme in the cardiovascular system, in patients with acute coronary syndromes.. Twenty-one consecutive patients with acute myocardial infarction (AMI), 14 patients with unstable angina, 11 patients with stable angina, and 20 control subjects were studied. The levels of vascular EC-SOD expression were assessed by the difference in plasma EC-SOD concentrations before and after intravenous heparan injection. In the patients with AMI, vascular EC-SOD expression (ng/mL) was significantly higher on day 1 after the onset of AMI (148+/-10) as compared with the control subjects (116+/-6, P<0.05). The vascular EC-SOD expression returned to the normal range on day 7 (104+/-8), and that level persisted thereafter. The vascular EC-SOD expression was also significantly higher in the patients with unstable angina (160+/-13) than in those with stable angina (122+/-10) or in the controls (116+/-6) (P<0.05 each). Moreover, in the patients with AMI, higher levels of vascular EC-SOD expression on day 1 were significantly associated with smaller myocardial infarct size (P<0.05).. This is the first clinical demonstration showing that vascular EC-SOD may be upregulated in acute coronary syndromes in humans in vivo. EC-SOD may play an important protective role against increased oxidative stress during acute ischemic coronary events.

Topics: Acute Disease; Adult; Aged; Aged, 80 and over; Aging; Coronary Disease; Enzyme Induction; Female; Heparitin Sulfate; Humans; Hypercholesterolemia; Male; Middle Aged; Muscle, Smooth, Vascular; Myocardial Infarction; Oxidative Stress; Oxygen Inhalation Therapy; Prospective Studies; Superoxide Dismutase

Several low molecular weight (LMW) heparin preparations, including dalteparin, enoxaparin and nadroparin, as well as the heparinoid danaparoid sodium, are approved for use in Australia. LMW heparins are replacing unfractionated heparin for the prevention and treatment of venous thromboembolism and the treatment of non-ST-segment-elevation acute coronary syndromes. The advantages of LMW heparins over unfractionated heparin include a longer half-life (allowing once-daily or twice-daily subcutaneous dosing), high bioavailability and predictable anticoagulant response (avoiding the need for dose adjustment or laboratory monitoring in most patients), and a low risk of heparin-induced thrombocytopenia and osteoporosis. Laboratory monitoring of LMW heparin therapy should be considered in newborns and children, patients with renal impairment, those who are pregnant, and those at the extremes of bodyweight (eg, < 40 kg or > 100 kg). LMW heparins should: be avoided or used with caution in patients undergoing neuraxial anaesthesia, owing to the potential for epidural haematoma formation; not be used (ie, are contraindicated) in patients with immune heparin-induced thrombocytopenia, as they may cross-react with anti-heparin antibodies. Conventional unfractionated heparin retains a role in the management of patients at high risk of bleeding, undergoing invasive procedures, and patients with renal failure owing to its shorter half-life, reversibility with protamine sulfate, and extrarenal metabolism. The heparinoid danaparoid sodium is effective for the treatment of heparin-induced thrombocytopenia.

Topics: Anticoagulants; Chondroitin Sulfates; Dermatan Sulfate; Drug Combinations; Heparin; Heparin, Low-Molecular-Weight; Heparinoids; Heparitin Sulfate; Humans; Myocardial Infarction; Thrombocytopenia; Venous Thrombosis

Administration of growth factors is emerging as a new therapeutic approach for the enhancement of collateral vessel formation in the ischemic heart. We have investigated the effects of intramyocardial delivery of FGF-2 in the presence and absence of heparin on angiogenesis in a porcine model of myocardial infarction. Yorkshire pigs were subjected to myocardial infarction by the placement of an embolization coil in the left anterior descending artery (n = 5). Four to five weeks after creation of an infarct, FGF-2 (10 micrograms) alone or in complex with heparin, heparan sulfate, or heparin agarose beads was injected either into the normal myocardium or along the infarct border area. Histologic evaluation of each injection site was performed 4 to 5 weeks post-injection. The effect of FGF-2 on angiogenesis was evaluated by determining the number of capillaries (diameter < 20 microns (and arterioles (> 20 microns with tunica media) in each area observed. The number of capillaries were not affected by the treatment of FGF-2 both in normal myocardium and infarct border area. However, in the normal myocardium, the number of arterioles were increased with the treatment of FGF-2 alone (85 +/- 59%, P < 0.04), FGF-2 plus heparin (281 +/- 193%, P < 0.004) and FGF-2-coated heparin beads (241 +/- 141%, P < 0.01), as compared to control. Delivery of FGF-2 into the infarct border area, also increased the number of arterioles when FGF-2 was given with heparin (736 +/- 154%, P < 0.001) or heparin beads (700 +/- 109%, P < 0.001), as compared to control. FGF-2 administered with heparin was the most effective method of enhancing angiogenesis as compared to FGF-2 alone, FGF-2 plus heparan sulfate, or FGF-2 coated heparin agarose beads.

Topics: Affinity Labels; Animals; Capillaries; Collateral Circulation; Coronary Vessels; Dose-Response Relationship, Drug; Fibroblast Growth Factor 2; Follow-Up Studies; Heart; Hemodynamics; Heparitin Sulfate; Injections, Intramuscular; Male; Myocardial Infarction; Neovascularization, Pathologic; Recombinant Proteins; Sepharose; Swine

Topics: Adult; Aged; Blood Coagulation Tests; Drug Combinations; Female; Fibrinolytic Agents; Glycosaminoglycans; Heart Block; Heparitin Sulfate; Humans; Male; Middle Aged; Mitral Valve Stenosis; Myocardial Infarction; Pericarditis; Thrombophlebitis

Gallium-67 citrate (67Ga) accumulation and various enzyme activities during the repair of rat heart with infarct-like lesions induced by isoproterenol (ISP) treatment were measured for 10 days after treatment. Serum creatine phosphokinase (CPK) and glutamic oxalacetic transaminase (GOT) activities were increased immediately after ISP treatment, reaching maximum levels of activity of 545 +/- 64 U/ml and 542 +/- 94 KU/ml, respectively, within 12 h. Uptake of 67Ga in the rat heart was elevated 12 h after ISP treatment, reaching a maximum on day 1 (0.473 +/- 0.015% dose/g heart). This pattern was essentially similar to the pattern of uronic acid content in the 1.2 M NaCl fraction, which contained mainly heparan sulfate (HS). The activity of glucose-6-phosphate dehydrogenase (G-6-PDH), a marker enzyme for fibrogenesis of damaged tissues, was also elevated 12 h after the ISP treatment, reaching a maximum of approximately 2.47 times that of the control heart on day 1. On the other hand, there were no significant changes in the 67Ga uptake and uronic acid content in any of the fractions of the liver and kidneys. These findings suggested that HS might be an acceptor for 67Ga accumulation during the repair of rat heart with infarct-like lesions, in accord with our previous results on CCl4-damaged rat liver.

Topics: Animals; Aspartate Aminotransferases; Creatine Kinase; Gallium Radioisotopes; Glucosephosphate Dehydrogenase; Heparitin Sulfate; Isoproterenol; Male; Myocardial Infarction; Radionuclide Imaging; Rats

Topics: Aged; Chondroitin Sulfates; Dermatan Sulfate; Female; Glycosaminoglycans; Heparitin Sulfate; Humans; Hyaluronic Acid; Male; Myocardial Infarction; Myocardium