Abstract
Ultrasound induced cavitation has been explored as a method of dissolving intravascular and microvascular thrombi in acute myocardial infarction. The purpose of this study was to determine the type of cavitation required for success, and whether longer pulse duration therapeutic impulses (sustaining the duration of cavitation) could restore both microvascular and epicardial flow with this technique. Accordingly, in 36 hyperlipidemic atherosclerotic pigs, thrombotic occlusions were induced in the mid-left anterior descending artery. Pigs were then randomized to either a) ½ dose tissue plasminogen activator (0.5 mg/kg) alone; or same dose plasminogen activator and an intravenous microbubble infusion with either b) guided high mechanical index short pulse (2.0 MI; 5 usec) therapeutic ultrasound impulses; or c) guided 1.0 mechanical index long pulse (20 usec) impulses. Passive cavitation detectors indicated the high mechanical index impulses (both long and short pulse duration) induced inertial cavitation within the microvasculature. Epicardial recanalization rates following randomized treatments were highest in pigs treated with the long pulse duration therapeutic impulses (83% versus 59% for short pulse, and 49% for tissue plasminogen activator alone; p<0.05). Even without epicardial recanalization, however, early microvascular recovery occurred with both short and long pulse therapeutic impulses (p<0.005 compared to tissue plasminogen activator alone), and wall thickening improved within the risk area only in pigs treated with ultrasound and microbubbles. We conclude that although short pulse duration guided therapeutic impulses from a diagnostic transducer transiently improve microvascular flow, long pulse duration therapeutic impulses produce sustained epicardial and microvascular re-flow in acute myocardial infarction.
Highlights
Over one million patients suffer from acute coronary syndromes each year in the United States alone, and over 200,000 of these are ST segment elevation myocardial infarction (STEMI) [1]
We have shown that the application of high mechanical index (MI) impulses from diagnostic two-dimensional or three-dimensional ultrasound systems can dissolve thrombi with microbubbles, even with transthoracic attenuation of the ultrasound impulses [16,17]
Note that inertial cavitation was present during the application of both the short and long therapeutic ultrasound (TUS) impulses used in the study
Summary
Over one million patients suffer from acute coronary syndromes each year in the United States alone, and over 200,000 of these are ST segment elevation myocardial infarction (STEMI) [1]. Both short and long term prognosis in these patients are improved when there is rapid restoration of flow in the obstructed infarct artery, if it is associated with restoration of microvascular flow [2,3,4,5].
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