title: In vivo antithrombotic synergy of oral heparin and arginine: endothelial thromboresistance without changes in coagulation parameters.
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.
authors: Oklahoma City, Oklahoma, USA.
authors: Bruce
authors: B
authors: Daniels
authors: Robert J
authors: RJ
authors: Linhardt
authors: Fuming
authors: F
authors: Zhang
authors: Wenjun
authors: W
authors: Mao
authors: Sandra M
authors: SM
authors: Wice
authors: Linda M
authors: LM
authors: Hiebert