Spontaneous redistribution after reperfusion: A unique property of AIP 201, an ultrasound contrast agent

Objectives. We sought to determine the mechanism of spontaneous redistribution of AIP 201 microbubbles after reperfusion from a single left heart injection performed during coronary occlusion. Background. AIP 201, an ultrasound contrast agent consisting of 10-μm sized microbubbles, has demonstrated spontaneous myocardial redistribution in preliminary studies. Methods. Myocardial video intensity (VI) and radiolabeled microsphere- derived myocardial blood flow (MBF) were measured serially after reperfusion in seven dogs undergoing an AIP 201 injection during coronary occlusion. The behavior of these bubbles was also assessed in the rat spinotrapezius muscle using intravital microscopy (IM), both with and without ultrasound. The effect of ultrasound on these bubbles was also determined in vitro. Results. A spontaneous and gradual increase in myocardial VI was noted after reperfusion, which was related to the magnitude of increase in MBF to that region (r = 0.82, p < 0.001). On IM, most of the microbubbles were seen entrapped in small arterioles. Some larger arterioles had aggregates of microbubbles that periodically became dislodged and moved downstream. This behavior was not affected in vivo by ultrasound. In vitro, however, microbubble aggregation was noted only during ultrasound exposure. Conclusions. The magnitude of redistribution of AIP 201 microbubbles to the reperfused myocardium is related to changes in MBF and occurs from their dislodgement from microbubble aggregates entrapped in large arterioles. In vitro microbubble aggregation seen during ultrasound exposure was not reproduced in vivo. These results may have important implications for studying the effects of interventions in acute coronary syndromes and after coronary artery bypass graft surgery.