Superiority of enoxaparin over heparin in combination with a GPIIb/IIIa receptor antagonist during coronary thrombolysis in dogs.

Abstract

It is known that a low-molecular-weight heparin (LMWH) is more effective than unfractionated heparin in unstable angina/non-Q-wave myocardial infarction (UA/NQMI) and the platelet GPIIb/IIIa receptors play an important role in acute myocardial infarction (AMI). Therefore, enoxaparin might have a similar advantage over heparin when used with a GPIIb/IIIa antagonist (RPR109891) in coronary thrombolysis. After induction of coronary thrombosis in anesthetized dogs, infusion of saline, enoxaparin, heparin, RPR109891, enoxaparin+RPR109891, or heparin+RPR109891 was initiated followed 15 min later by recombinant tissue plasminogen activator (rt-PA). The incidence of reperfusion in the enoxaparin+RPR109891- and the heparin+RPR109891-treated groups was similar, but time to reperfusion tended to be shorter for enoxaparin versus heparin. Only 43% of the vessels reoccluded in the enoxaparin+RPR109891 group, compared to 100% vessels in the heparin+RPR109891 group. Enoxaparin+RPR109891 maintained flow for a significantly longer time compared to saline, enoxaparin, heparin, and heparin+RPR109891. Enoxaparin+RPR109891 and heparin+RPR109891 increased the template bleeding time by 2- and 3-fold and activated partial thromboplastin time (APTT) by 1.3- and 3-fold, respectively. These data suggest that enoxaparin is more effective and potentially safer than heparin when combined with a GPIIb/IIIa receptor antagonist during rt-PA-induced coronary thrombolysis.

• Authors: S S Rebello, C J Kasiewski, R G Bentley, S R Morgan, V Chu, J S Bostwick, S I Klein, M H Perrone, R J Leadley
• Journal: Thrombosis research (Thromb Res) Vol. 102 Issue 3 Pg. 261-71 (May 01 2001) ISSN: 0049-3848 [Print] United States
• PMID: 11369420 (Publication Type: Journal Article)

Chemical References

• Enoxaparin
• Fibrinolytic Agents
• Oligopeptides
• Platelet Aggregation Inhibitors
• Platelet Glycoprotein GPIIb-IIIa Complex
• klerval
• Heparin
• Tissue Plasminogen Activator

Topics

• Animals
• Blood Flow Velocity (drug effects)
• Coronary Thrombosis (drug therapy)
• Disease Models, Animal
• Dogs
• Drug Therapy, Combination
• Enoxaparin (administration & dosage, standards, therapeutic use)
• Female
• Fibrinolytic Agents (administration & dosage, pharmacology)
• Heparin (administration & dosage, pharmacology, standards)
• Male
• Oligopeptides (administration & dosage, pharmacology)
• Platelet Aggregation Inhibitors (administration & dosage, therapeutic use)
• Platelet Glycoprotein GPIIb-IIIa Complex (antagonists & inhibitors)
• Therapeutic Equivalency
• Thrombolytic Therapy (methods)
• Time Factors
• Tissue Plasminogen Activator (administration & dosage, pharmacology)
• Vascular Patency (drug effects)