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(Circulation. 2009;119:1378-1385.)
© 2009 American Heart Association, Inc.

Coronary Heart Disease

Diagnostic Ultrasound Combined With Glycoprotein IIb/IIIa–Targeted Microbubbles Improves Microvascular Recovery After Acute Coronary Thrombotic Occlusions

Feng Xie, MD; John Lof, MS; Terry Matsunaga, PhD; Reena Zutshi, PhD; Thomas R. Porter, MD

From the Department of Internal Medicine, Section of Cardiology, University of Nebraska Medical Center, Omaha (F.X., J.L., T.R.P.); Department of Radiology Research, University of Arizona, Tucson (T.M.); and ImaRx Therapeutics, Inc, Tucson, Ariz (R.Z.).

Correspondence to Feng Xie, MD, University of Nebraska Medical Center, 982265 Nebraska Medical Center, Omaha NE 68198-2265. E-mail fxie{at}unmc.edu

Received September 29, 2008; accepted December 29, 2008.

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.

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CLINICAL PERSPECTIVE

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Clinical Summaries
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