The thrombolytic potency of LMW-heparin compared to urokinase in a rabbit jugular vein clot lysis model.
Since the beginning of the clinical use of low molecular weight (LMW) heparins their thrombolytic or profibrinolytic potency has been a matter of controversial discussions. Regarding this problem, the aim of our study was to test a LMW-heparin (Sandoparin) in an in vivo model comparing its lytic activity to unfractionated heparin and urokinase at different doses. For this purpose a newly developed short-term rabbit jugular vein clot lysis model was developed. Urokinase infused at doses of 3300, 6600 and 10,000 U/kg to control animals for one hour showed a clear dose-dependent clot lysis. Test animals were injected with a bolus of 0.5 mg/kg of LMW-heparin followed by a constant infusion of either 0.5, 1.0 or 2.0 mg/kg for one hour. A similar dose-dependent effect was observed for LMW-heparin as for urokinase. Unfractionated heparin did not exhibit a dose-dependent lytic activity in this model. No lysis was found in rabbits treated with saline. These findings suggest that the LMW-heparin tested exhibits a dose-dependent in vivo lytic activity which can be compared to clinically effective doses of urokinase, and that this activity is not present with unfractionated heparin.
Bacher
P
P
Department of Pathology, Loyola University Medical Center, Maywood, Illinois.
Welzel
D
D
Iqbal
O
O
Hoppensteadt
D
D
Callas
D
D
Walenga
J M
JM
Fareed
J
J
D000818:Animals; D004195:Disease Models, Animal; D004305:Dose-Response Relationship, Drug; D004353:Drug Evaluation, Preclinical; D005343:Fibrinolytic Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000627:therapeutic use*; D007601:Jugular Veins; D008297:Male; D011817:Rabbits; D015912:Thrombolytic Therapy; D013924:Thrombophlebitis / Q000188:drug therapy*; D014568:Urokinase-Type Plasminogen Activator / Q000008:administration & dosage / Q000627:therapeutic use*
D005343:Fibrinolytic Agents; D006495:Heparin, Low-Molecular-Weight; D014568:Urokinase-Type Plasminogen Activator