Comparison of a synthetic antithrombin III-binding pentasaccharide and standard heparin as an adjunct to coronary thrombolysis.
The effects on alteplase-induced thrombolysis of the synthetic ATIII-binding pentasaccharide SR90107A/ORG 31540 (synthetic pentasaccharide, SP) and of standard heparin (SH) were compared in a copper coil model of coronary artery thrombosis in 6 groups of 10 dogs. After 1 h of occlusion, all animals received intravenously alteplase and aspirin, and were randomly assigned to a 2 h infusion of either saline, or one of two doses of SH (100 IU/kg bolus plus 50 IU/kg/h infusion, or 200 IU/kg bolus plus 100 IU/kg/h infusion), or one of three doses of SP (100 nmol/kg bolus plus 50 nmol/kg/h infusion, 200 nmol/kg bolus plus 100 nmol/kg/h infusion, or 400 nmol/kg bolus plus 200 nmol/kg/h infusion). Coronary angiography was performed every 10 min for 4 h. Appropriate doses of SP and SH enhanced alteplase-induced thrombolysis to a similar extent. In contrast, SP was devoid of any anti-IIa activity or aPTT prolongation.
Pislaru
S V
SV
Department of Cardiology, University Hospitals Leuven, Belgium.
Pislaru
C
C
Zhu
X
X
Arnout
J
J
Stassen
T
T
Vanhove
P
P
Herbert
J M
JM
Meuleman
D G
DG
Van de Werf
F
F
D000818:Animals; D000925:Anticoagulants / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D000990:Antithrombin III / Q000037:antagonists & inhibitors / Q000378:metabolism*; D001241:Aspirin / Q000008:administration & dosage / Q000627:therapeutic use; D001760:Bleeding Time; D017023:Coronary Angiography; D003328:Coronary Thrombosis / Q000000981:diagnostic imaging / Q000188:drug therapy*; D003331:Coronary Vessels / Q000187:drug effects / Q000473:pathology; D004285:Dogs; D004353:Drug Evaluation, Preclinical; D004359:Drug Therapy, Combination; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D006487:Hemostasis / Q000187:drug effects; D006493:Heparin / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D009844:Oligosaccharides / Q000008:administration & dosage / Q000378:metabolism / Q000627:therapeutic use*; D010314:Partial Thromboplastin Time; D011897:Random Allocation; D015912:Thrombolytic Therapy; D010959:Tissue Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D000925:Anticoagulants; D005343:Fibrinolytic Agents; D009844:Oligosaccharides; C064764:PENTA; D000990:Antithrombin III; D006493:Heparin; D010959:Tissue Plasminogen Activator; D001241:Aspirin