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Journal of Pharmacology And Experimental Therapeutics Fast Forward
First published on September 13, 2004; DOI: 10.1124/jpet.104.075283

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*Compound via MeSH
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Medline Plus Health Information
*Cardiomyopathy
*Heart Attack


Received for publication August 3, 2004.
Revised September 9, 2004.
Accepted for publication September 13, 2004.

Sulodexide (KRX-101) Attenuates Myocardial Ischemia/Reperfusion Injury and the Deposition of C-Reactive Protein in Areas of Infarction without Affecting Hemostasis

D. Adam Lauver 1, Erin A. Booth 1, Andrew J. White 1, Enrique Poradosu 2, Benedict R. Lucchesi 3*

1 University of Michigan Medical School 2 Keryx Biopharmaceuticals 3 Univeristy of Michigan Medical School

* Address correspondence to: E-mail: benluc{at}umich.edu

Abstract

Several glycosaminoglycans (GAGs) have been demonstrated to protect the ischemic heart against reperfusion injury, in part, by modulating activation of the complement cascade. The present study assessed the cardioprotective effects of sulodexide (KRX-101), a mixture of GAGs composed of 80% low molecular weight heparin and 20% dermatan sulfate. KRX-101 differs from other GAGs (e.g. heparin) in that it has limited anticoagulant efficacy and can be administered orally. The experimental protocol was designed to determine if KRX-101 could protect the ischemic myocardium. Anesthetized, New Zealand white rabbits underwent 30 minutes of coronary artery occlusion. Intravenous doses of KRX-101 (0.5 mg/kg, n = 10) or drug diluent (n = 10) were administered at the end of regional ischemia and at each hour of reperfusion. Infarct size, as a percentage of the area at risk, was calculated for both groups. Myocardial infarct size was 31.3 ± 4.1% in the vehicle and 17.3 ± 3.2% in the KRX-101 treated animals (p < 0.05 vs. vehicle). Activated partial thromboplastin times determined at baseline (pre-ischemia) and at each hour of reperfusion (n = 4) were not significantly different between vehicle and KRX-101 treated groups (p = ns). Myocardial injury was further assessed by measuring serum levels of cardiac-specific troponin I. KRX-101 administration significantly reduced (p < 0.05) the serum concentration of troponin I during reperfusion. The results suggest that KRX-101 may be an effective adjunctive agent in myocardial revascularization procedures, without the risk of increased bleeding.


Key words: Activated Partial Thromboplastin Time, Cardiac-specific Troponin I, Complement, Glycosaminoglycan, Immunofluorescence, Infarct Size


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