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% lowmolecular 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 ϭ 10) or drug diluent (n ϭ 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 Ϯ 4.1% in the vehicleand 17.3 Ϯ 3.2% in the KRX-101-treated animals (p Ͻ 0.05 versus vehicle). Activated partial thromboplastin times determined at baseline (preischemia) and at each hour of reperfusion (n ϭ 4) were not significantly different between vehicle-and KRX-101-treated groups (p ϭ N.S.). Myocardial injury was further assessed by measuring serum levels of cardiac-specific troponin I. KRX-101 administration significantly reduced (p Ͻ 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.

Disodium Disuccinate Astaxanthin (Cardax) Attenuates Complement Activation and Reduces Myocardial Injury following Ischemia/Reperfusion

“…Although these results did not achieve statistical significance, clear evidence of a downward trend in this serum marker of irreversible myocardial tissue injury was obtained. The reduced statistical power observed in this study versus previous results obtained in our laboratory for this marker (Lauver et al, 2005) may have resulted from the curtailed period of reperfusion in the current study. There may have been insufficient time for cTnI to reach peak plasma concentrations in this study.…”

“…The immunofluorescent method for detection of CRP was based on protocols previously developed in our laboratory (Lauver et al, 2005). Briefly, tissue samples used for infarct size determination were fixed in 10% buffered formalin immediately after the completion of the experimental protocol.…”

Sulodexide: A Renewed Interest in This Glycosaminoglycan

“…In addition, selective GAGs are known to possess anti-complement activity in addition to their classical roles as anticoagulants. Recently we reported that sulodexide effectively reduced myocardial infarct size after ischemia and reperfusion in the rabbit heart when administered periodically throughout the four hour reperfusion period (48) (Fig. 1).…”

“…Deposition of a sufficient number of the lytic membrane attack complexes on a nucleated target cell results in disruption of the cell membrane and ultimately cell lysis. Intravenous administration of 0.5 mg/kg sulodexide, commencing immediately upon reperfusion and at hourly intervals during reperfusion was associated with a significant decrease in myo-D. A. LAUVER AND B. R. LUCCHESI cardial infarct size expressed as a percentage of the area at risk when compared with vehicle-treated control rabbits (48).…”

Heat shock treatment results in increased recruitment of labeled PMN following myocardial infarction

“…We have used an in vivo biomarker of MI used clinically that has been shown to correlate temporally with the degree of myocardial cell death (30). Troponin release measured in the serum 24 h post-MI by ELISA was shown to be no different between groups, suggesting similar infarct size and therefore likely not accounting for the increased labeled PMN migration in the HSϩMI group.…”