Utilization of modified diagnostic ultrasound and microbubbles to reduce myocardial infarct size.

Abstract

We sought to determine whether guided high mechanical index (MI) impulses from a diagnostic ultrasound transducer during an intravenous microbubble infusion could augment low-dose fibrinolytic therapy in treating acute myocardial infarction (ST segment elevation myocardial infarction, STEMI). Acute thrombotic occlusions of the left anterior descending were created in 32 atherosclerotic pigs. Fourteen historical control pigs received half dose of tissue plasminogen activator alone (half tPA), while the subsequent 18 were randomised to (a) 1.0 mg/kg tPA (full-dose tPA); (b) low-dose tPA (0.5 mg/kg) and an intravenous microbubble infusion where guided transthoracic high MI impulses were applied intermittently to the risk area (guided high MI/half tPA) or (c) guided high MI impulses and microbubbles alone (guided high MI alone). Angiographic recanalisation, ST segment resolution and wall thickening (WT) at 60 min were compared between all pigs, while indexed infarct size at 48 h was compared in the 18 randomised pigs. Recanalisation rates improved from 36% for half dose tPA alone to 83% with the addition of guided high MI impulses, while it was 50% for full-dose tPA and guided high MI alone. WT recovery within the risk area following treatment was highest for guided high MI/half tPA (p=0.007 compared with full-dose tPA; ANOVA), and indexed infarct size was lowest (p<0.05 compared to full-dose tPA). Guided high MI-induced microbubble cavitation from a diagnostic transducer added to low-dose tPA can immediately improve regional function and reduce infarct size in acute STEMI. Clinical Trials.gov NCT02170103.