Generic placeholder image

Recent Patents on Cardiovascular Drug Discovery

Editor-in-Chief

ISSN (Print): 1574-89011
ISSN (Online): 2212-3962

Heparins with Reduced Anti-Coagulant Activity Reduce Myocardial Reperfusion Injury

Author(s): William H. Barry and Thomas P. Kennedy

Volume 6 , Issue 2 , 2011

Page: [148 - 157] Pages: 10

DOI: 10.2174/157489011795933855

Price: $65

Abstract

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


Rights & Permissions Print Export Cite as
© 2022 Bentham Science Publishers | Privacy Policy