gms | German Medical Science

Objective: Hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged as an optional therapy for spontaneous intracerebral hemorrhage (ICH). However, the effect of hematoma volume reduction is often counteracted by rtPA-induced delayed edema as a side effect. Transcranial ultrasound has been applied in combination with rtPA lysis for the treatment of intracranial arterial occlusion. An advantage of endosongraphy in contrast to transcranial sonography is its higher frequency at a lower range protecting surrounding tissue. The aim of this study was to evaluate the lysis of blood clots using an endosonography catheter and a reduced dose of rtPA in a novel clot model to achieve hematoma lysis with non-toxic doses of rtPA.

Method: In vitro blood clots were produced from 25 ml of human blood, incubated 4 h at 37 C°. An external ventricular drainage (EVD) was placed into all clots, mimicking the intracranial situation of a lysis catheter, and connected to a drainage system. The clots were submerged 10 cm in water and 15 cm above the ground of a 37 C° water bath. 4 experimental groups each consisting of 3 blood clots were analyzed in different treatment situations. Group 1 has no further treatment, in group 2 a suboptimal dose of 0.3 mg rtPA was administered, in group 3 in addition to rtPA 1 h ultrasound exposure by a 10 F endosonography catheter was achieved in B-mode (10 mHz) and Doppler-mode (6.5 mHz) to create maximum ultrasound power, and in group 4 only ultrasound was applied. In groups 2 and 3 the drainage was closed for 1 h after rtPA injection, in group 1 and 4 it remained open. Clots were weighed before and 1 h after treatment. Statistical analysis was performed by a t-Test.

Results: It was possible to create a reliable clot model for in vitro investigation. The post-treatment clot volume of the control group was 53.7% ±8%, rtPA group 51.9% ±3%, ultrasound group 51.7% ±10.5% and rtPA+ultrasound group 43.8% ±5%. Comparing the groups, there was a significant reduction of clot volume in the rtPA+ultrasound compared to the control group (P<0.05) and a tendency compared to the rtPA group.

Conclusions: Preliminary results of our experimental in vitro study of clot lysis show an additive effect of lysis induction by minimal rtPA dose and sono-thrombolysis. Thus a possible combined treatment of sono-thrombolysis and a minimal rtPA dose could achieve sufficient hematoma volume reduction and reduced cytotoxic effects of rtPA on brain tissue. This needs further investigation in an animal model of ICH.