Linked Life Data

9684808

Source:http://linkedlifedata.com/resource/pubmed/id/9684808

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1998-10-29
pubmed:abstractText
Current therapeutic use of heparin as an adjunct to thrombolytic therapy for myocardial infarction is suboptimal with respect to efficacy and bleeding risk. In a rat carotid arterial thrombolysis model (FeCl3-induced injury) we evaluated the combined effect of tPA (2.0 mg/kg/30 min) with our potent injectable direct thrombin inhibitor, BCH-2763 (Ki 0.11 nM; MW 1.5 kDa), which, unlike heparin, inhibits bound and free thrombin; comparisons were with standard heparin (SH), other direct thrombin inhibitors, r-hirudin (MW 6.5 kDa) and hirulog (MW 2.3 kDa), or tPA alone. Time to lysis (TL), patency time (PT), aPTT (fold increase) and bleeding time (BT) were determined. ED100 (100% of rats reperfused) for BCH-2763, hirulog or r-hirudin was 1, 3 or 2 mg/kg/60 min, respectively; 67% of rats reperfused with SH at the highest dose tested (220 U/kg/60 min) and 43% with tPA alone. At these doses, TL (min) was shorter (p < 0.01) with BCH-2763 (0.5 +/- 0.1), hirulog (3.3 +/- 2.3) or r-hirudin (2.3 +/- 1.0) than SH (66.3 +/- 30.8) or tPA alone (93.4 +/- 21.4). The aPTT fold increase after 15 min infusion was markedly greater (p < 0.001) for SH (32.0 +/- 0.8) than BCH-2763 (3.7 +/- 0.5), hirulog (5.2 +/- 0.3) or r-hirudin (4.5 +/- 0.8) in combination with tPA or tPA alone (1.1 +/- 0.1). In addition, the BT (min) for BCH-2763 (3.0 +/- 0.4) was similar to tPA alone (1.6 +/- 0.3), but prolonged (p < 0.05) for hirulog (7.5 +/- 2.7), r-hirudin (6.6 +/- 0.8) or SH (7.3 +/- 1.8). Comparisons at same aPTT fold increase revealed that in combination with tPA, BCH-2763 required a lower anticoagulant level to shorten the TL and prolong the PT than hirulog, r-hirudin or SH. Thus, in this rat arterial thrombolysis model direct thrombin inhibitors are more effective than SH as antithrombotic adjuncts to tPA. BCH-2763 is effective at a lower gravimetric dose and more modest aPTT fold increase than hirulog or r-hirudin with less alteration in haemostasis, which may confer an improved safety index.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0340-6245
pubmed:author
pubmed:issnType
Print
pubmed:volume
80
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
186-91
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9684808-Amino Acid Sequence, pubmed-meshheading:9684808-Animals, pubmed-meshheading:9684808-Anticoagulants, pubmed-meshheading:9684808-Carotid Arteries, pubmed-meshheading:9684808-Disease Models, Animal, pubmed-meshheading:9684808-Fibrinolysis, pubmed-meshheading:9684808-Fibrinolytic Agents, pubmed-meshheading:9684808-Heparin, pubmed-meshheading:9684808-Hirudin Therapy, pubmed-meshheading:9684808-Hirudins, pubmed-meshheading:9684808-Injections, pubmed-meshheading:9684808-Male, pubmed-meshheading:9684808-Molecular Sequence Data, pubmed-meshheading:9684808-Oligopeptides, pubmed-meshheading:9684808-Peptide Fragments, pubmed-meshheading:9684808-Rats, pubmed-meshheading:9684808-Rats, Sprague-Dawley, pubmed-meshheading:9684808-Recombinant Proteins, pubmed-meshheading:9684808-Thrombin, pubmed-meshheading:9684808-Tissue Plasminogen Activator
pubmed:year
1998
pubmed:articleTitle
Effective use of BCH-2763, a new potent injectable direct thrombin inhibitor, in combination with tissue plasminogen activator (tPA) in a rat arterial thrombolysis model.
pubmed:affiliation
BioChem Therapeutic Inc., Laval, Quebec, Canada.
pubmed:publicationType
Journal Article, Comparative Study