Abstract 11295: Sonoreperfusion Therapy for Microvascular Obstruction Using Microbubbles and Low Dose tPa

Abstract

Listen

Translate article

Background: Despite successful epicardial recanalization in acute myocardial infarction, adequate microvascular perfusion often fails due to embolization of thrombotic debris causing microvascular obstruction (MVO). We previously reported that long tone burst high mechanical index ultrasound (US) + microbubbles (MB) restored microvascular perfusion (sonoreperfusion, SRP) in an in vitro flow model using PBS perfusate. We sought to demonstrate SRP efficacy in whole blood perfusate with and without low dose tPa. Methods: The model comprised a 4 mm diameter phantom vessel with a 40 μm pore mesh to simulate a microvascular cross section and upstream pressure reflecting thrombus burden. Bovine whole blood and 2x10 6 /ml lipid MB (~3 μm) infused at 0.75 ml/min simulated microvascular flow. Bovine blood microthrombi were injected onto the mesh until upstream pressure was 30 mmHg. US was delivered for 20 min (1 MHz, 1.5 MPa peak negative pressure, 3 sec pulse interval, 1000-5000 cycles) with and without low dose tPa (2.5 μg/ml) during measurement of upstream pressure to assess SRP efficacy (n = 3-7). Lytic rate (rate of pressure drop in the first 4 min) and lytic index (1/area under pressure-time curve) quantified SRP efficacy. Results: In whole blood, lytic rate was 2.6 ± 1.5 mmHg/min at 1000 cycles US+MB increasing to 7.3 ± 3.2 mmHg/min at 5000 cycles US+MB (p<0.01) without tPa. The lytic index was similar for tPa only (2.0 ± 0.5) x 10 -3 mmHg -1 .min -1 and 5000 cycles US + MB without tPa (2.3 ± 0.5) x 10 -3 mmHg -1 .min -1 (p=0.5) but increased to (3.6 ± 0.8) x 10 -3 mmHg -1 .min -1 (p<0.01) for 5000 cycles US+MB+tPa, indicating an additive effect of tPa with US + MB therapy (Fig 1). Conclusions: In whole blood, US + MB therapy restored microvascular perfusion. Similarly to our previous findings with PBS perfusate, SRP efficacy varied with cycle length in the presence of MB. The addition of tPa increased SRP efficacy in blood, suggesting a potential additive effect of low dose tPa and US + MB therapy in vivo .