Enoxaparin (Clexane, Lovenox), a low molecular weight heparin, enhances t-PA-induced coronary thrombus lysis in anesthetized dogs without inducing hypocoagulability.
Rhone-Poulenc Rorer, Centre de Recherches de Vitry-Alfortville, Vitry-Sur-Seine, France.
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.
PMID: 1329253 [PubMed - indexed for MEDLINE]