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Heparins with Reduced Anti-Coagulant Activity Reduce Myocardial Reperfusion Injury

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Heparin which is desulfated at the 2-O and 3-O positions (ODSH) has reduced anti-coagulant properties, and reduced interaction with heparin antibodies. Because of the reduced anti-coagulant effect, ODSH can be safely administered to animals and humans intravenously at doses up to 20 mg/kg, resulting in a serum concentration of up to 250 μg/ml. Administration of ODSH causes a 35% reduction in infarct size in dogs and pigs subjected to coronary artery occlusion and reperfusion when given 5 min before reperfusion. ODSH has anti-inflamatory effects, manifest as a decrease in neutrophil infiltration into ischemic tissue at high doses, but this effect does not entirely account for the reduction in infarct size. ODSH decreases Na+ and Ca2+ loading in isolated cardiac myocytes subjected to simulated ischemia. This effect appears due to an ODSH-induced reduction in an enhanced Na+ influx via the Na channel in the membrane of cardiac myocyes caused by oxygen radicals generated during ischemia and reperfusion. Reduction in Na+ influx decreases Ca2+ loading by reducing Ca2+ influx via Na/Ca exchange, thus reducing Ca2+ - dependent reperfusion injury. ODSH does not appear to interact with antibodies to the heparin/platelet factor 4 complex, and does not cause heparin-induced thrombocytopenia. Because of these therapeutic and safety considerations, ODSH would appear to be a promising heparin derivative for prevention of reperfusion injury in humans undergoing thrombolytic or catheter-based reperfusion for acute myocardial infarction. The review article discussed the use of heparin and the discussion of some of the important patents, including: US6489311; US7478358; PCTUS2008070836 and PCTUS2009037836.

Keywords: Anticoagulant; Calcium; Calcium Loading; O-desulfated heparin; glycation end products; heparin; myocardium; reperfusion injury; sodium; sodium calcium exchange

Document Type: Research Article


Publication date: May 1, 2011

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  • Recent Patents on Cardiovascular Drug Discovery publishes review articles on recent patents in the field of cardiovascular drug discovery e.g. novel bioactive compounds, analogs & targets. A selection of important and recent patents on cardiovascular drug discovery is also included in the journal. The journal is essential reading for all researchers involved in cardiovascular drug design and discovery.

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