In Vivo Antithrombotic Synergy of Oral Heparin and Arginine: Endothelial Thromboresistance Without Systemic Anticoagulation

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Authors
Daniels, B.
Linhardt, Robert J.
Zhang, F.
Mao, W.
Wice, S.
Hiebert, L.
Issue Date
2006
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Article
Language
ENG
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Biology , Chemistry and chemical biology , Chemical and biological engineering , Biomedical engineering
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Abstract
On the basis of suggested clinical efficacy in an uncontrolled study in ninety-seven patients with unstable angina, an animal study was conducted to investigate antithrombotic synergy between orally administered heparin and arginine. A rat venous thrombosis model tested the difference in thrombus formation when heparin (7.5 mg/kg) and arginine (113 mg/kg) were administered, alone or in combination, by stomach tube with a minimum of 20 rats/group. Oral heparin, arginine, and heparin plus arginine reduced thrombus formation by 50%, 75%, and 90%, respectively, when compared to saline administration. Heparin was recovered from endothelium, yet there was little or no observable plasma anticoagulant activity. An orally administered low-molecular- weight anticoagulant glycosaminoglycan mixture, sulodexide (7.5 mg/kg), showed an 88% reduction in stable thrombus formation when administered alone but showed no synergy with oral arginine. A 28-day study with oral sulodexide (2.9 mg/ kg) and arginine (43.9 mg/kg), 20 rats/group, showed antithrombotic activity with minimal anticoagulant activity indicating suitability for long term treatment. These findings suggest the endothelial localization of heparin and a synergistic antithrombotic effect for orally administered heparin and arginine.
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Thrombosis and Haemostasis, 95, 865-873
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Full Citation
In Vivo Antithrombotic Synergy of Oral Heparin and Arginine: Endothelial Thromboresistance Without Systemic Anticoagulation, B. Daniels, R.J. Linhardt, F. Zhang, W. Mao, S. Wice, L. Hiebert, Thrombosis and Haemostasis, 95, 865-873, 2006.
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Thieme Medical Publishers
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