Linked Life Data

8836007

Source:http://linkedlifedata.com/resource/pubmed/id/8836007

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
1996-12-31
pubmed:abstractText
Argatroban was evaluated in three models of thrombosis in the rabbit: the Wessler model (thromboplastin plus stasis of the left jugular vein), an arteriovenous shunt model, and a model of arterial thrombosis induced by endothelial and intimal damage of the left femoral artery. Calcium heparin was used as a comparator. Both substances inhibited thrombus formation in the Wessler model with ID50 values of 0.32 and 0.16 mg/kg intravenous bolus for argatroban and heparin respectively, with similar changes in thrombin time (4 to 5 times control) and activated partial thromboplastin time (APTT) (1.6 to 2.1 times control) for both substances at antithrombotic doses. The ID50 values of both substances were 2.4 micrograms/kg/min (argatroban) and 0.5 microgram/kg/min (heparin). When they were administered by continuous infusion, no significant effects on the APTT were noted. In the arteriovenous shunt, the ID50 values for argatroban and heparin (respectively) were 0.16 and 0.07 mg/kg intravenous bolus, and 4.5 and 2.8 micrograms/kg/min intravenous infusion. Vessel clamping followed immediately by electrical stimulation (5 mA direct current, 5 minutes) of the left femoral artery leads to the formation of an occlusive thrombus approximately 30 minutes after clamping. Argatroban infused for 60 minutes before the vascular lesion and throughout the 90 minute observation period led to a dose-dependent delay in arterial occlusion with significant effects seen at 5 micrograms/kg/min with five of eight animals showing normal femoral blood flow at 90 minutes postlesion at 20 micrograms/kg/min; no significant increases (Dunnett's test) in APTT were noted with argatroban. Heparin was without effect even at 40 micrograms/kg/min, despite an eight-fold increase in APTT at 20 micrograms/kg/min and values of more than 300 seconds at 40 micrograms/kg/min. Thus, in models of arterial but not venous thrombosis, argatroban is a more potent antithrombotic agent than heparin on a weight basis, with antithrombotic effects at a much lower degree of systemic anticoagulation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0094-6176
pubmed:author
pubmed:issnType
Print
pubmed:volume
22
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
233-41
pubmed:dateRevised
2006-3-7
pubmed:meshHeading
pubmed:year
1996
pubmed:articleTitle
Antithrombotic activity of argatroban in experimental thrombosis in the rabbit.
pubmed:affiliation
Cardiovascular Department, Synthélabo Recherche, Bagneux, France.
pubmed:publicationType
Journal Article