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

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. (Circulation. 2009; 119: 1378-1385.)