Diagnostic ultrasound combined with glycoprotein IIb/IIIa-targeted microbubbles improves microvascular recovery after acute coronary thrombotic occlusions

Abstract

Background: The high mechanical index (MI) impulses from a diagnostic ultrasound transducer may be a method of recanalizing acutely thrombosed vessels if the impulses are applied only when microbubbles are channeling through the thrombus.

Methods and results: In 45 pigs with acute left anterior descending thrombotic occlusions, a low-MI pulse sequence scheme (contrast pulse sequencing) was used to image the myocardium and guide the delivery of high-MI (1.9 MI) impulses during infusion of either intravenous platelet-targeted microbubbles or nontargeted microbubbles. A third group received no diagnostic ultrasound and microbubbles. All groups received half-dose recombinant prourokinase, heparin, and aspirin. Contrast pulse sequencing examined replenishment of contrast within the central portion of the risk area and guided the application of high-MI impulses. Angiographic recanalization rates, resolution of ST-segment elevation on ECG, and wall thickening were analyzed. Pigs receiving platelet-targeted microbubbles had more rapid replenishment of the central portion of the risk area (80% versus 40% for nontargeted microbubbles; P=0.03) and higher epicardial recanalization rates (53% versus 7% for prourokinase alone; P=0.01). Replenishment of contrast within the risk area (whether with platelet-targeted microbubbles or nontargeted microbubbles) was associated with both higher recanalization rates and even higher rates of ST-segment resolution (82% versus 21% for prourokinase alone; P=0.006). ST-segment resolution occurred in 6 pigs (40%) treated with microbubbles who did not have epicardial recanalization, of which 5 had recovery of wall thickening.

Conclusions: Intravenous platelet-targeted microbubbles combined with brief high-MI diagnostic ultrasound impulses guided by contrast pulse sequencing improve both epicardial recanalization rates and microvascular recovery.

Figure 1

The upper panel demonstrates an example of no replenishment within the lateral or central portions of the RA following a high MI impulse (left panel) at 10 minutes into treatment. The lower panel shows an example of replenishment only in the lateral portions of the RA following a high MI impulse at 15 minutes into treatment. Images were obtained after contrast plateau intensity had been reached (right panel).

Figure 2

The upper panel shows an example of partial replenishment of the central portion of the RA at the plateau intensity following a high MI impulse (left panel). , again at 20 minutes into treatment The lower panel shows an example of complete replenishment of the RA (central and lateral portions) following the delivery of high MI impulses (left panel) at 10 minutes into treatment.

Figure 3

Pigs randomized to diagnostic ultrasound and targeted IV microbubbles (MB) had significantly higher recanalization rates than control (lytic therapy alone) at 30 minutes of treatment. Non-targeted IV microbubbles achieved a similar recanalization rate (50%) at 60 minutes. *p=0.02 compared to control

Figure 4

Angiograms of a left anterior descending artery before and after 30 minutes of intermittent high MI diagnostic ultrasound (guided by CPS) and intravenous platelet-targeted microbubbles.

Figure 5

Example of the improvement in the electrocardiogram observed in a pig after ultrasound and targeted microbubbles with lytic. Note that the ST-segment elevation observed at 0 mibutes almost totally resolves after 30 minutes of treatment with diagnostic ultrasound (DUS) and microbubbles (MB). In comparison, ST-segment elevation almost no changes after 30 minutes of lytic alone treatment.

Figure 6

The percentage of pigs who exhibited partial or complete replenishment of myocardial contrast within the central portion of the risk area when randomized to receive guided diagnostic ultrasound and either non-targeted or platelet-targeted microbubbles following left anterior descending coronary thrombotic occlusion. *p=0.03