PMID- 15116252
OWN - NLM
STAT- MEDLINE
DCOM- 20041222
LR  - 20181130
IS  - 0340-6245 (Print)
IS  - 0340-6245 (Linking)
VI  - 91
IP  - 5
DP  - 2004 May
TI  - Orally administered heparins prevent arterial thrombosis in a rat model.
PG  - 919-26
AB  - 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.
FAU - Pinel, Cory
AU  - Pinel C
AD  - University of Saskatchewan, Department of Veterinary Biomedical Sciences, Western 
      College of Veterinary Medicine, 52 Campus Drive, Saskatoon SK S7N 5B4, Canada.
FAU - Wice, Sandra M
AU  - Wice SM
FAU - Hiebert, Linda M
AU  - Hiebert LM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Germany
TA  - Thromb Haemost
JT  - Thrombosis and haemostasis
JID - 7608063
RN  - 0 (Heparin, Low-Molecular-Weight)
RN  - 7UQ7X4Y489 (Tinzaparin)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Administration, Oral
MH  - Animals
MH  - Blood Flow Velocity
MH  - Carotid Artery Thrombosis/drug therapy/*prevention & control
MH  - Disease Models, Animal
MH  - Drug Evaluation, Preclinical
MH  - Endothelium, Vascular/metabolism
MH  - Heparin/administration & dosage/*pharmacokinetics/pharmacology
MH  - Heparin, Low-Molecular-Weight/administration & 
      dosage/pharmacokinetics/pharmacology
MH  - Kinetics
MH  - Male
MH  - Rats
MH  - Rats, Wistar
MH  - Thrombosis/drug therapy/prevention & control
MH  - Time Factors
MH  - Tinzaparin
EDAT- 2004/04/30 05:00
MHDA- 2004/12/23 09:00
CRDT- 2004/04/30 05:00
PHST- 2004/04/30 05:00 [pubmed]
PHST- 2004/12/23 09:00 [medline]
PHST- 2004/04/30 05:00 [entrez]
AID - 04050919 [pii]
AID - 10.1160/TH03-08-0527 [doi]
PST - ppublish
SO  - Thromb Haemost. 2004 May;91(5):919-26. doi: 10.1160/TH03-08-0527.