Orally administered heparins prevent arterial thrombosis in a rat model.
Our previous studies demonstrated that orally administered heparins prevent thrombosis in a rat jugular vein thrombosis model, where bovine unfractionated heparin (UFH) and the low molecular weight heparin tinzaparin reduced thrombotic incidence by 50% at 7.5 and 0.1 mg/kg, respectively. Our objectives were to determine if similar antithrombotic effects of oral heparin could be observed in an arterial thrombosis model. In this model, filter paper soaked in 30% ferric chloride was applied to the exposed rat carotid artery. A flowmeter recorded blood flow over a 60 min period determining time when the thrombus began forming (TTB) and time till occlusion (TTO). Immediately following, the thrombus was removed, dried and weighed 24 h later. Bovine UFH (7.5 mg/kg), tinzaparin (0.1 mg/kg) or saline was administered by stomach tube at 2, 5 and 25 h prior to thrombus initiation. TTB was significantly increased when UFH was given at 5 and 25 h but not 2 h prior, and when tinzaparin was given at 5 but not 2 or 25 h prior compared to rats given oral saline. TTO was significantly increased for both UFH and tinzaparin when given 5 and 25 h but not 2 h prior (one-way ANOVA). There was no difference in TTO and TTB between UFH and tinzaparin treated groups. A trend in reduction in thrombus weight was observed for UFH at 5 and 25 h prior and tinzaparin at 5 h prior to thrombus initiation (one-way ANOVA). Although no significant changes were observed in activated partial thromboplastin times, Heptest or anti-Xa activity from plasma of heparin treated rats, endothelial heparin concentrations were significantly greater than controls for UFH at 5 h and for tinzaparin at 2, 5, and 24 h. Thus, heparins administered by the oral route are effective antithrombotic agents in arterial as well as venous models.
Pinel
Cory
C
University of Saskatchewan, Department of Veterinary Biomedical Sciences, Western College of Veterinary Medicine, 52 Campus Drive, Saskatoon SK S7N 5B4, Canada.
Wice
Sandra M
SM
Hiebert
Linda M
LM
D000284:Administration, Oral; D000818:Animals; D001783:Blood Flow Velocity; D002341:Carotid Artery Thrombosis / Q000188:drug therapy / Q000517:prevention & control*; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004730:Endothelium, Vascular / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000494:pharmacology; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology; D007700:Kinetics; D008297:Male; D051381:Rats; D017208:Rats, Wistar; D013927:Thrombosis / Q000188:drug therapy / Q000517:prevention & control; D013997:Time Factors; D000078222:Tinzaparin
D006495:Heparin, Low-Molecular-Weight; D000078222:Tinzaparin; D006493:Heparin