Destruction of Contrast Microbubbles by Ultrasound

Abstract

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 83Ϯ5% of baseline at an MI of 1.6) and a transient MI-dependent increase in coronary perfusion pressure (to 120Ϯ6% 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 3.6Ϯ1.4%. Conclusions-Simultaneous

Augmentation of AAV-mediated cardiac gene transfer after systemic administration in adult rats

“…[38][39][40][41] However, clinically irrelevant conditions were mostly used in these studies, such as extremely high doses of microbubbles, continuous high energy ultrasound exposure, open chest ultrasound exposure or ex vivo sonication of hearts. Using similar parameters as described in our experiments, other studies have demonstrated no relevant cardiac adverse events.…”

Controlled nanoparticle release from stable magnetic microbubble oscillations

“…16,18,19 Such rapid and asymmetrical collapse (that is, cavitation) results in high shear flows, microjets and microstreaming 21 that damage surrounding tissues, such as the endothelium. [4][5][6][7] Furthermore, the synchronous burst release of drugs could exceed toxic limits, limiting the clinical application of these MMBs.…”

“…This high energy and microstreaming may damage the surrounding tissues. [4][5][6][7] Our strategy involves stimulating stable oscillating MMBs at their resonant frequencies using ultrasound. MMBs are synthesized by coating a gas core with iron oxide NPs and drug-containing NPs.…”

“…The ability to remotely control the release of NPs via the oscillation of stable MMBs poses opportunities for targeted drug delivery through/into tissues that are difficult to diffuse through or penetrate without damage to surrounding tissues by bubble cavitation. [4][5][6][7] …”

Evans Blue Staining of Cardiomyocytes Induced by Myocardial Contrast Echocardiography in Rats: Evidence for Necrosis Instead of Apoptosis

“…Myocardial contrast echocardiography (MCE) using diagnostic ultrasound scanners at high Mechanical Index (MI) has been associated with capillary rupture in the myocardium resulting in petechiae-like erythrocyte extravasation sites in animal models (Ay et al 2001;Li et al 2004). In addition, histological evidence of cardiomyocyte contraction band necrosis immediately after exposure has been shown for diagnostic ultrasound with commercial contrast agent in rats (Miller et al 2005a).…”