Abstract 15990: Microbubble-Mediated Sonothrombolysis With Long Tone Burst Ultrasound for the Treatment of Microvascular Microembolization: An in vivo Study
Background: Despite successful epicardial coronary artery reperfusion by percutaneous coronary intervention (PCI), microembolization (mEMB) of thrombotic debris into the microcirculation limits myocardial salvage during acute myocardial infarction (AMI). Thrombolysis using ultrasound (US) and i.v. microbubbles (MB) is a theranostic approach that detects microvascular “low reflow” and also induces MB cavitation in the embolized microcirculation to cause lysis and restore perfusion. We previously reported the superior efficacy of long tone burst US + MB in an in vitro model of mEMB. To test the hypothesis that this approach is effective in vivo, we developed a new rat hindlimb model of mEMB.
Methods: Venous blood was used to create microemboli (diameter 19.2 ± 0.6 μm). In 16 rats (9 treatment and 7 control), lines were placed in the femoral artery for injection of emboli and treatment MB. An imaging transducer was placed on the biceps femoris, perpendicular to a single element 1MHz treatment transducer. Perfusion imaging (7MHz, CPS) was performed during i.v. lipid MB infusion at baseline, and 10 min after mEMB to confirm low flow. Therapeutic US was delivered (5000 cycles, PRF 0.33 Hz, 1.5 MPa) for 10 min during simultaneous femoral arterial MB infusion. Perfusion imaging was performed after treatment. Controls with identical mEMB received no US-MB. Microvascular volume was measured as peak muscle videointensity (VI).
Results: Peak VI decreased 90% after mEMB of 0.5-0.3 ml microthrombi (VI from 36.4 ± 6.7 to 3.1 ± 1.1 dB, p<0.01). After US-MB, VI increased 8-fold (to 24.8 ± 7.2 dB, p<0.05) and was equivalent to baseline. In 7 controls, perfusion remained low after mEMB compared to baseline (p<0.001), and did not recover (Fig 1).
Conclusion: We have developed an in vivo model to simulate distal mEMB such as occurs after primary PCI for AMI. Long pulse length US and MB have a therapeutic effect on microvascular perfusion, and may be a valuable adjunct to reperfusion therapy for AMI.
- © 2013 by American Heart Association, Inc.