Abstract
The aim of this study is to establish a microvascular thrombosis model using a hamster cheek pouch membrane suited to evaluate the thrombolytic process in vivo. Furthermore, the effect of anticoagulants such as unfractionated heparin (UFH), low molecular weight heparin (LMWH), and recombinant hirudin (r-hir) on thrombolysis induced by recombinant tissue plasminogen activator (rt-PA) was investigated in this model.
Microvascular thrombus in hamster cheek pouch membrane was produced by the irradiation of filtered light with the intravascular administration of fluorescein sodium. The thrombus, with 99% stenosis of the vascular lumen, was used for the evaluation of thrombolytic process. The thrombolytic process, induced by the administration of rt-PA (36×104IU/kg·hr, 72×104IU/kg·hr, 108×104IU/kg·hr), was monitored through high gain camera connected to microscope and VTR. Then thrombolytic process was assessed by three parameters, % stenosis of vessel, % length of thrombus, and % area of thrombus which were calculated with computed video analyzer. Above mentioned anticoagulants were administered respectively with rt-PA and the thrombolytic process was evaluated by the same method. PT, APTT, fibrinogen, plasminogen, and α2-PI were measured in citrated plasma.
The size of the thrombus formed in this study was increased in proportion to the irradiated area by the filtered light. Thrombus size was decreased depending on the dose of rt-PA, however there seemed to be the optimum dose for rt-PA infusion. Compared with UFH and LMWH, r-hir accelerated thrombolysis by rt-PA potently with less decrease of plasma plasminogen level.
This microvascular thrombosis model was considered to be excellent for the evaluation of thrombolytic agents in vivo, and the superiority of r-hir compared to heparins in thrombolytic therapy was suggested.
