Doppler sonography enhances rtPA-induced fibrinolysis in an in vitro clot model of spontaneous intracerebral hemorrhages

• Published in: PloS one Vol. 14; no. 1; p. e0210810
• Main Authors: Masomi-Bornwasser, Julia, Winter, Philipp, Neulen, Axel, Kantelhardt, Sven R, König, Jochem, Kempski, Oliver, Ringel, Florian, Keric, Naureen
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 17.01.2019; Public Library of Science (PLoS)
• Subjects: Acoustic attenuation; Biology and Life Sciences; Blood; Blood coagulation; Care and treatment; Catheters; Cerebral Hemorrhage - therapy; Combined Modality Therapy; Edema; Engineering and Technology; Fibrinolysis; Fibrinolysis - drug effects; Hematoma; Hemorrhage; Humans; In vitro methods and tests; In Vitro Techniques; Incubation; Intracerebral hemorrhage; Ischemia; Lysis; Medical instruments; Medicine and Health Sciences; Models, Cardiovascular; Neurosurgery; Physical Sciences; Probes; Proof of Concept Study; Rarefaction; Research and Analysis Methods; Side effects; Squama; Stroke; Studies; Temperature; Thrombolytic Therapy - methods; Tissue plasminogen activator; Tissue Plasminogen Activator - therapeutic use; Transcranial Doppler ultrasonography; Ultrasonic imaging; Ultrasonic Therapy - instrumentation; Ultrasonic Therapy - methods; Ultrasonography, Doppler, Transcranial - instrumentation; Ultrasound; Water treatment; Weight reduction; Germany
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0210810

Transcranial Doppler (TCD) was shown to enhance intravascular fibrinolysis by rtPA in ischemic stroke. Studies revealed that catheter-based administration of rtPA induces lysis of intracerebral hemorrhages (ICH). However, it is unknown whether TCD would be suitable to enhance rtPA-induced fibrinolysis in patients with ICH. The aim of this study was to assess the potential of TCD to enhance rtPA-induced fibrinolysis in an in vitro clot system. Reproducible human blood clots of 25 ml were incubated in a water bath at 37°C during treatments. They were weighed before and after 6 different treatments: (I) control (incubation only), (II) rtPA only, (III) one Doppler probe, (IV) two Doppler probes placed vis-à-vis, (V) one probe and rtPA and (VI) two probes and rtPA. To quantify lysis of the blood clots and attenuation of the Doppler through a temporal squama acoustic peak rarefaction pressure (APRP) was measured in the field of the probes. Temperature was assessed to evaluate possible side effects. Clot weight was reduced in all groups. The control group had the highest relative end weight of 70.2%±7.2% compared to all other groups (p<0,0001). Most efficient lysis was achieved using (VI) 2 probes and rtPA 36.3%±4.4% compared to (II, III, IV) (p<0.0001; p = 0.0002; p = 0.048). APRP was above lysis threshold (535.5±7.2 kPa) using 2 probes even through the temporal squama (731.6±32.5 kPa) (p = 0.0043). There was a maximal temperature elevation of 0.17±0.07°C using both probes. TCD significantly enhances rtPA-induced lysis of blood clots, and the effect is amplified by using multiple probes. Our results indicate that bitemporal TCD insonation of hematomas could be a new and safe approach to enhance fibrinolysis of ICH´s treated with intralesional catheter and rtPA.