Contrast Ultrasound Imaging of the Aorta Alters Vascular Morphology and Circulating von Willebrand Factor in Hypercholesterolemic Rabbits

Objectives Ultrasound contrast agents (UCAs) are intravenously infused microbubbles that add definition to ultrasonic images. Ultrasound contrast agents continue to show clinical promise in cardiovascular imaging, but their biological effects are not known with confidence. We used a cholesterol‐fed rabbit model to evaluate these effects when used in conjunction with ultrasound (US) to image the descending aorta. Methods Male New Zealand White rabbits (n = 41) were weaned onto an atherogenic diet containing 1% cholesterol, 10% fat, and 0.11% magnesium. At 21 days, rabbits were exposed to contrast US at 1 of 4 pressure levels using either the UCA Definity (Lantheus Medical Imaging, Inc, North Billerica, MA) or a saline control (n = 5 per group). Blood samples were collected and analyzed for lipids and von Willebrand factor (vWF), a marker of endothelial function. Animals were euthanized at 42 days, and tissues were collected for histologic analysis. Results After adjustment for pre‐exposure vWF, high‐level US (in situ [at the aorta] peak rarefactional pressure of 1.4 or 2.1 MPa) resulted in significantly lower vWF 1 hour post exposure (P = .0127; Padj < .0762). This difference disappeared within 24 hours. Atheroma thickness in the descending aorta was lower in animals receiving the UCA compared to animals receiving saline. Conclusions Contrast US affected the descending aorta, as evidenced by two separate outcome measures. These results may be a first step in elucidating a previously unknown biological effect of UCAs. Further research is warranted to characterize the effects of this procedure.