Destruction of Contrast Microbubbles by Ultrasound: Effects on Myocardial Function, Coronary Perfusion Pressure, and Microvascular Integrity

Background— Recent experimental data indicate that ultrasound-induced destruction of ultrasound contrast microbubbles can cause immediate rupture of the microvessels in which these microbubbles are located. Methods and Results— To examine the functional and morphological significance of these findings in the heart, isolated rabbit hearts were perfused retrogradely with buffer containing ultrasound contrast agents and were insonated at increasing levels of acoustic energy with a broadband transducer emitting at 1.8 MHz and receiving at 3.6 MHz and operated in the triggered mode (1 Hz). At the end of each experiment, the hearts were fixed in glutaraldehyde and examined with light microscopy. Neither exposure to ultrasound alone or to contrast alone affected left ventricular developed pressure. By contrast, simultaneous exposure to contrast and ultrasound resulted in a reversible, transient mechanical index (MI)-dependent decrease in left ventricular developed pressure (to 83±5% of baseline at an MI of 1.6) and a transient MI-dependent increase in coronary perfusion pressure (to 120±6% of baseline at an MI of 1.6). Myocardial lactate release also showed significant increases with increasing MIs. Macroscopically, areas of intramural hemorrhage were identified over the beam elevation in hearts exposed to both contrast and high-MI ultrasound. Light microscopy revealed the presence of capillary ruptures, erythrocyte extravasation, and endothelial cell damage. The mean percentage of capillaries ruptured at an MI of 1.6 was 3.6±1.4%. Conclusions— Simultaneous exposure of isolated rabbit hearts to ultrasound and contrast agents results in an MI-dependent, transient depression of left ventricular contractile function, a rise in coronary perfusion pressure, an increase in lactate production, and limited capillary ruptures.