title: Sulodexide attenuates myocardial ischemia/reperfusion injury and the deposition of C-reactive protein in areas of infarction without affecting hemostasis.
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 mass 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 whether KRX-101 could protect the ischemic myocardium. Anesthetized New Zealand white rabbits underwent 30 min 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 versus vehicle). Activated partial thromboplastin times determined at baseline (preischemia) and at each hour of reperfusion (n = 4) were not significantly different between vehicle- and KRX-101-treated groups (p = N.S.). 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.
authors.affiliation: Department of Pharmacology, University of Michigan Medical School, 1301 MSRB III, Ann Arbor, MI 48109, USA.
authors.forename: D Adam
authors.initials: DA
authors.lastname: Lauver
authors.forename: Erin A
authors.initials: EA
authors.lastname: Booth
authors.forename: Andrew J
authors.initials: AJ
authors.lastname: White
authors.forename: Enrique
authors.initials: E
authors.lastname: Poradosu
authors.forename: Benedict R
authors.initials: BR
authors.lastname: Lucchesi
mesh_terms: D000818:Animals; D016718:Arachidonic Acid / Q000494:pharmacology; D015415:Biomarkers; D001777:Blood Coagulation / Q000187:drug effects; D001792:Blood Platelets / Q000187:drug effects; D001794:Blood Pressure / Q000187:drug effects; D002097:C-Reactive Protein / Q000378:metabolism*; D005455:Fluorescent Antibody Technique; D006025:Glycosaminoglycans / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects; D006339:Heart Rate / Q000187:drug effects; D006487:Hemostasis / Q000187:drug effects*; D008297:Male; D009203:Myocardial Infarction / Q000378:metabolism*; D015428:Myocardial Reperfusion Injury / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010314:Partial Thromboplastin Time; D011817:Rabbits; D013917:Thrombin / Q000494:pharmacology
chemical_list: D015415:Biomarkers; D006025:Glycosaminoglycans; D016718:Arachidonic Acid; C007858:glucuronyl glucosamine glycan sulfate; D002097:C-Reactive Protein; D013917:Thrombin