gms | German Medical Science

Objective: Catheter-based hematoma lysis with recombinant tissue plasminogen activator (rtPA) has emerged to a well-established therapy of spontaneous intracerebral hemorrhage (ICH). A small clinical trial showed effectiveness of intralesional sonothrombolysis in combination with rtPA. Previously we could show a significant increase of rtPA-based fibrinolysis by endosonography in an in vitro model of ICH. The aim of this study was to assess the potential of sonothrombolysis by an endosonography catheter in vivo (porcine ICH-model). We present preliminary results of an ongoing experimental work.

Methods: Deutsche Landrasse male pigs (30–35 kg) were sedated and intubated. Continuous intra-arterial blood pressure was recorded via an arterial femoral line. An intracranial pressure- (ICP) sensor was placed in the left frontal lobe through a twist drill burr hole for monitoring reasons. A right frontal ICH was produced by infusion of 10 ml arterial autologous blood via a continuous infusion (3ml/min). A cranial MRI was performed immediately after ICH placement and 2 h after treatment. The animals were randomized in 4 treatment groups: group 1 (drainage only n=2), group 2 (drainage+rtPA n=3), group 3 (drainage+endosonography, 10 MHz b-mode n=3), and group 4 (drainage+endosonography+rtPA n=3). Liquefied hematoma was drained by a gravity-based system for 1 hour. Hematoma volumes were assessed by segmentation using a neuronavigation planning software (iPlan, Brainlab^®). Animals were euthanized 6 h after ictus. Brains were fixed in 4 % PFA, paraffin embedded and sliced for histological analysis. Perihematomal tissue was morphologically analyzed in HE-staining and further characterized by immunohistochemistry.

Results: Hematoma volume reduction in the group 1 was 2.95±3.36%, 40.71±2.758% in group 2, 34.7±6.39% in group 3 and 54.5± 6.91% in group 4. Compared to the control group the groups 2, 3 and 4 showed significant differences in overall hematoma volume reduction (group 1 vs. 2 P=0.0043; group 1 vs. 3 P=0.0139; group 1 vs. 4 P=0.0042). The combination treatment group achieved the greatest hematoma volume reduction and was significant different compared to group 3 (P=0.0132). Mean arterial blood pressure (MAP) and ICP values did not differ between the treatment groups. MAP ranged from 64.9 to 87.4 mmHg and mean preoperative ICP values from 8.1-11.4 mmHg. ICP increased at the time of ICH placement till 91 and decreased again in the following 15 min until 14 mmHg. The HE-staining showed no morphological differences in the perihematomal zone.

Conclusion: The combination of sonography and rtPA seems to be a more effective and safe fibrinolytic therapy compared to rtPA alone, while sonography serves as an accelerator for fibrinolysis. Additionally this endosonography catheter can be applied as a diagnostic imaging tool in b-mode and Doppler mode, which allows realtime intracranial monitoring.