Table 1.
Studies assessing the influence of microbubbles and ultrasound on thrombolysis
| Author(s)/reference | Microbubble | Target in vivo/in vitro | TL, US, MB | US frequency | Outcome |
|---|---|---|---|---|---|
| Tachibana and Tachibana [4] | Albumin MB (albunex) | In vitro thrombus | Urokinase, US and MB | 170 kHz, 0.5 W/cm2 | Significantly increased thrombolysis with thrombolytics, US and MB |
| Kondo et al. [22] | Air-filled MB with galactose/palmitic acid shell | In vitro white thrombus | t-PA, US and MB | 10 MHz, 0.5−1.0 W/cm2 | Significant enhancement of thrombus reduction by MB |
| Nishioka et al. [23] | DDFP | In vitro and in vivo canine iliofemoral arteries | MB and US | 20 kHz, 1.5 W/cm2 | Increased clot disruption and recanalisation with US and MB |
| Porter et al. [24] | Air-filled MB/PESDA MB | In vitro thrombus | Urokinase, US and MB | 20 kHz, 40 W/cm2 | Significantly better thrombolysis of PESDA than air-MB. Optimal thrombolysis with UK and MB |
| Birnbaum et al. [25] | PESDA MB | In vivo canine iliofemoral artery | US and MB | Up to 160 W/cm2 | Significantly higher recanalisation rate with MB |
| Siegel et al. [26] | DDFP/PESDA | In vivo rabbit iliofemoral artery and canine LAD | SK, US, MB | 20−37 kHz, 1.5−160 W/cm2 | Increased clot dissolution with US, MB and SK |
| Culp et al. [27] | PESDA tagged with eptifibatide | In vivo pigs ascending pharyngeal artery | US and MB | 1 MH, 2 W/cm2 | Improvement of recanalisation rate in eptifibatide tagged PESDA |
| Xie et al. [15] | Glycoprotein IIb/IIIa targeted MB/Lipid MB | In vivo pigs LAD occlusion | PUK, US, MB | 1.5 MHz, MI 1.9 | Significantly higher epicardial recanalisation and microvascular recovery with targeted MB |
| CLOTBUST investigators [9] | – | In vivo middle cerebral artery Phase 2 trial | t-PA and US | 2 MHz | Ultrasound augments t-PA induced arterial recanalisation |
| Molina et al. [10] | Galactose MB (Levovist) | In vivo middle cerebral artery Phase 2 trial | t-PA, US, MB | 2 MHz | MB safely induces acceleration of US enhanced thrombolysis |
| Cohen et al. [28] | – | In vivo STEMI Phase 2 trial | rt-PA and US | 27 kHz | No major adverse events |
| Eggers et al. [29] | – | In vivo middle cerebral artery | rt-PA and US | 1.8 MHz, 179 mW/cm2 | Improvement in short-term clinical outcome and recanalisation rate |
| Molina et al. [30] | MRX-801 | In vivo Phase 1–2 trial acute ischemic stroke | t-PA and US | 2 MHz | Trend towards higher recanalisation rates in treatment group |
TL Thrombolytic, MB microbubble, US ultrasound, (r)t-PA (recombinant) tissue plasminogen activator, PESDA perfluorocarbon-exposed sonicated dextrose albumin, (P)UK (pro)-urokinase, DDFP dodecafluoropentane, LAD left artery descending; SK streptokinase