Enoxaparin (Clexane, Lovenox), a low molecular weight heparin, enhances t-PA-induced coronary thrombus lysis in anesthetized dogs without inducing hypocoagulability.
An occlusive coronary thrombus was obtained in barbiturate anesthetized dogs within 60 min following the angiographic placement of a copper coil into the left descending coronary artery. This thrombus persisted for the 60 min experimental period, within which the effects of i.v. t-PA (10 micrograms/kg/min for 30 min) alone or combined with i.v. heparin (0.63 mg/kg twice) or enoxaparin (1.5 mg/kg twice) were evaluated. t-PA alone achieved recanalization for 20 min in only 2 out of the 5 dogs studied. Combination of t-PA with either heparin or enoxaparin produced this effect in all the 5 dogs studied. In dogs treated with t-PA associated to either heparin or enoxaparin, the thrombus weight was smaller (decreases of 34% and 44% respectively) than in animals given t-PA alone. The plasma amidolytic activity, expressed as t-PA activity, was greater 15 min after the beginning of t-PA infusion, in dogs pretreated with either heparin or enoxaparin than in animals given t-PA alone. Conversely, during t-PA infusion, the apparent t-PA inhibitor and antiplasmin activities were no longer measurable in the plasma, but reappeared 10 min after the end of t-PA infusion. Plasma coagulation time was not modified by t-PA, but was slightly prolonged (2-fold) by enoxaparin and markedly (7-fold) by heparin on initiation of t-PA infusion. Plasma anti-IIa activity was 3-fold higher in dogs pretreated with heparin as opposed to enoxaparin. On the contrary, both compounds increased similarly plasma anti-Xa activity. In conclusion, these results indicate that enoxaparin, like heparin, enhances the thrombolytic effects of t-PA. This favourable effect occurs independently of a plasma hypocoagulable state, which was clearly produced by heparin but not enoxaparin. Its mechanism may be the significant elevation of plasma t-PA activity produced by both heparin and enoxaparin during t-PA infusion.
Mestre
M
M
Rhone-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry-Sur-Seine, France.
Uzan
A
A
Sedivy
P
P
Cavero
I
I
D000595:Amino Acid Sequence; D000818:Animals; D003328:Coronary Thrombosis / Q000097:blood / Q000188:drug therapy*; D004285:Dogs; D004357:Drug Synergism; D065427:Factor Xa Inhibitors; D005260:Female; D005343:Fibrinolytic Agents / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D006474:Hemorrhagic Disorders / Q000139:chemically induced; D006493:Heparin / Q000494:pharmacology / Q000627:therapeutic use; D006495:Heparin, Low-Molecular-Weight / Q000494:pharmacology / Q000627:therapeutic use* / Q000633:toxicity; D006801:Humans; D008297:Male; D008969:Molecular Sequence Data; D011516:Prothrombin / Q000037:antagonists & inhibitors; D015912:Thrombolytic Therapy / Q000009:adverse effects; D010959:Tissue Plasminogen Activator / Q000494:pharmacology / Q000627:therapeutic use*; D000979:alpha-2-Antiplasmin / Q000032:analysis
D065427:Factor Xa Inhibitors; D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D000979:alpha-2-Antiplasmin; D011516:Prothrombin; C025337:Factor IIa; D006493:Heparin; D010959:Tissue Plasminogen Activator