chondroitin-sulfates 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

To test the hypothesis that the use of chondroitin sulfate (CS) or glucosamine reduces the risk of acute myocardial infarction (AMI).. Case-control study nested in a primary cohort of patients aged 40 to 99 years, using the database BIFAP during the 2002-2015 study period. From this cohort, we identified incident cases of AMI and randomly selected five controls per case, matched by exact age, gender, and index date. Adjusted odds ratios (AOR) and 95% confidence interval (CI) were computed through a conditional logistic regression. Only new users of CS or glucosamine were considered.. A total of 23,585 incident cases of AMI and 117,405 controls were included. Of them, 89 cases (0.38%) and 757 controls (0.64%) were current users of CS at index date, yielding an AOR of 0.57 (95%CI: 0.46-0.72). The reduced risk among current users was observed in both short-term (<365 days, AOR = 0.58; 95%CI: 0.45-0.75) and long-term users (>364 days AOR = 0.56; 95%CI:0.36-0.87), in both sexes (men, AOR = 0.52; 95%CI:0.38-0.70; women, AOR = 0.65; 95%CI:0.46-0.91), in individuals over or under 70 years of age (AOR = 0.54; 95%CI:0.38-0.77, and AOR = 0.61; 95%CI:0.45-0.82, respectively) and in individuals at intermediate (AOR = 0.65; 95%CI:0.48-0.91) and high cardiovascular risk (AOR = 0.48; 95%CI:0.27-0.83), but not in those at low risk (AOR = 1.11; 95%CI:0.48-2.56). In contrast, the current use of glucosamine was not associated with either increased or decreased risk of AMI (AOR = 0.86; 95%CI:0.66-1.08).. Our results support a cardioprotective effect of CS, while glucosamine seems to be neutral. The protection was remarkable among subgroups at high cardiovascular risk.

Topics: Aged; Aged, 80 and over; Case-Control Studies; Chondroitin Sulfates; Cohort Studies; Databases, Factual; Electronic Health Records; Female; Glucosamine; Humans; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Risk Assessment; Risk Factors; Spain

Following myocardial infarction (MI), degradation of extracellular matrix (ECM) by upregulated matrix metalloproteinases (MMPs) especially MMP-2 decreases tissue mechanical properties, leading to cardiac function deterioration. Attenuation of cardiac ECM degradation at the early stage of MI has the potential to preserve tissue mechanical properties, resulting in cardiac function increase. Yet the strategy for efficiently preventing cardiac ECM degradation remains to be established. Current preclinical approaches have shown limited efficacy because of low drug dosage allocated to the heart tissue, dose-limiting side effects, and cardiac fibrosis. To address these limitations, we have developed a MMP-2 inhibitor delivery system that can be specifically delivered into infarcted hearts at early stage of MI to efficiently prevent MMP-2-mediated ECM degradation. The system was based on an injectable, degradable, fast gelation, and thermosensitive hydrogel, and a MMP-2 specific inhibitor, peptide CTTHWGFTLC (CTT). The use of fast gelation hydrogel allowed to completely retain CTT in the heart tissue. The system was able to release low molecular weight CTT over 4 weeks possibly due to the strong hydrogen bonding between the hydrogel and CTT. The release kinetics was modulated by amount of CTT loaded into the hydrogel, and using chondroitin sulfate and heparin that can interact with CTT and the hydrogel. Both glycosaminoglycans augmented CTT release, while heparin more greatly accelerated the release. After it was injected into the infarcted hearts for 4 weeks, the released CTT efficiently prevented cardiac ECM degradation as it not only increased tissue thickness but also preserved collagen composition similar to that in the normal heart tissue. In addition, the delivery system significantly improved cardiac function. Importantly, the delivery system did not induce cardiac fibrosis. These results demonstrate that the developed MMP-2 inhibitor delivery system has potential to efficiently reduce adverse myocardial remodeling and improve cardiac function.

Topics: Animals; Chondroitin Sulfates; Drug Carriers; Drug Liberation; Extracellular Matrix; Heparin; Humans; Hydrogels; Male; Matrix Metalloproteinase 2; Matrix Metalloproteinase Inhibitors; Myocardial Infarction; Myocytes, Cardiac; Peptides, Cyclic; Rats; Rats, Sprague-Dawley

During 2007 and 2008 it is likely that millions of patients in the US received heparin contaminated (CH) with oversulfated chondroitin sulfate, which was associated with anaphylactoid reactions. We tested the hypothesis that CH was associated with serious morbidity, mortality, intensive care unit (ICU) stay and heparin-induced thrombocytopenia following adult cardiac surgery.. We conducted a single center, retrospective, propensity-matched cohort study during the period of CH and the equivalent time frame in the three preceding or the two following years. Perioperative data were obtained from the institutional record of the Society of Thoracic Surgeons National Database, for which the data collection is prospective, standardized and performed by independent investigators. After matching, logistic regression was performed to evaluate the independent effect of CH on the composite adverse outcome (myocardial infarction, stroke, pneumonia, dialysis, cardiac arrest) and on mortality. Cox regression was used to determine the association between CH and ICU length of stay. The 1∶5 matched groups included 220 patients potentially exposed to CH and 918 controls. There were more adverse outcomes in the exposed cohort (20.9% versus 12.0%; difference  =  8.9%; 95% CI 3.6% to 15.1%, P < 0.001) with an odds ratio for CH of 2.0 (95% CI, 1.4 to 3.0, P < 0.001). In the exposed group there was a non-significant increase in mortality (5.9% versus 3.5%, difference = 2.4%; 95% CI, -0.4 to 3.5%, P  =  0.1), the median ICU stay was longer by 14.1 hours (interquartile range -26.6 to 79.8, S = 3299, P = 0.0004) with an estimated hazard ratio for CH of 1.2 (95% CI, 1.0 to 1.4, P = 0.04). There was no difference in nadir platelet counts between cohorts.. The results from this single center study suggest the possibility that contaminated heparin might have contributed to serious morbidity following cardiac surgery.

Topics: Adolescent; Adult; Aged; Aged, 80 and over; Cardiac Surgical Procedures; Chondroitin Sulfates; Drug Contamination; Female; Heart Arrest; Heparin; Humans; Intensive Care Units; Length of Stay; Logistic Models; Male; Middle Aged; Myocardial Infarction; Odds Ratio; Pneumonia; Renal Dialysis; Retrospective Studies; Risk Factors; Stroke; Survival Analysis

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

Topics: Adult; Aged; Chondroitin Sulfates; Female; Glycosaminoglycans; Heparin; Humans; Hyaluronic Acid; Male; Middle Aged; Myocardial Infarction

The experimental models used by investigators to study myocardial infarction have been considered as to their possible application for use in studies of the healing of myocardial infarction. The information concerning healing has also been surveyed. In general, the healing of the myocardial infarct in the dog and in the rat is by connective tissue replacement of the injured tissue resulting in a scar similar to skin scars. In the healing process, there is an early increase of glycoproteins, possibly from serum, and of hyaluronic acid in the injured tissue. Much of this is part of the general reaction to injury and may not be part of the healing process. Somewhat later (about 2-3 days in the dog) the chondroitin-4-sulfate fraction begins to rise. Collagen biosynthesis increases at the same time although this relationship is not well established. Much later (after 30 days in dog) the chondroitin-4-sulfate content of the injured tissue begins to decrease. At this time the scar is well formed. Much later (as late as 171 days) the scar in the myocardium still contains elevated amounts of chondroitin-4-sulfate. The dermatan sulfate is increased and the hyaluronic acid slightly decreased as compared to undamaged myocardium. These changes are typical in maturing scars of skin.

Topics: Animals; Chondroitin Sulfates; Coronary Vessels; Dermatan Sulfate; Disease Models, Animal; Dogs; Glycosaminoglycans; Heart; Humans; Hyaluronic Acid; Middle Aged; Myocardial Infarction; Rats; Wound Healing

Topics: Animals; Chondroitin Sulfates; Dermatan Sulfate; Dogs; Glycosaminoglycans; Hyaluronic Acid; Myocardial Infarction; Periodic Acid-Schiff Reaction; Time Factors; Wound Healing

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