THE EFFECT OF RT-PA ALONE AND IN COMBINATION WITH THROMBIN INHIBITORS IN A MODEL OF CEREBROVASCULAR THROMBOSIS IN THE RABBIT

Occlusivevasculardisorders,bothvenousandarterial,aresomeofthemostcommoncausesofmorbidityandmortalityindevelopedcountries.Theaimoftherapyinsuchconditionsis,firstly,torestoreandmaintainbloodflowtotheaffectedtissueororgan,andsecondly,torestorethesystemtothenormalhaemostaticstatewithoutovercompensatingandproducingcomplicationssuchashaemorrhage.Thrombolyticagents,suchasrecombinanttissueplasminogenactivator(rt-PA),arewidelyusedinthetreatmentofpatientswithacutemyocardialinfarction.However,successful…

THE EFFECT OF RT-PA ALONE AND IN COMBINATION WITH THROMBIN INHIBITORS IN A MODEL OF CEREBROVASCULAR THROMBOSIS IN THE RABBIT

Sustained accumulatin of 111 indium-labelled platelets is induced in the cerebral vascuiature or rabbits by bolus intracarotid (i. c. ) administration or thrombin (90 U/kg). Bolus i. c. injection of the fibrinolytic, recombiuant tissue plasminogen activator (rt-PA), 1 miu after thrombin,produced significant inbibition of the. platelet accumulation, albeit substantially less than that produced by 1 min Pretreatment. Hirulogm, PPACK and rt-PA alone had no direct effect on the hasalcirculating levels of 111 In-labedlled platelets in the pulmonary or cranial vasculature at the doses used.Hirulongm and PPACK did not enhance the ability or inrusion or a threshold dose of rt-PA to decrease an established cerebrovascular thromhosis, whereas Defibrotide plus rt-PA produced a significant reduction on accumulated plateiets. These results suggest that fiibrin deposition .plays the impor tant role in the induction and maintenance of the. sustained cerebral platelet accumulation induced bythrombin in this model and Defibrotide can .enhance the pro-fibrinolytic effect of rt-PA although thisProperty is not shared by direct thrombin inhibitors. The sustained platelet accumulation in the cranial vasculature in this model does not appear to be a result or continued generation or endogenousthrombin.