Double, Double, Toil and Trouble: Nitric Oxide or Xenon Bubble

Christy K. Holland – Christy.Holland@uc.edu
Department of Internal Medicine, Division of Cardiovascular Health and Disease and
Department of Biomedical Engineering
University of Cincinnati
Cardiovascular Center 3935
231 Albert Sabin Way
Cincinnati, Ohio  45267-0586
https://www.med.uc.edu/ultrasound
office:  +1 513 558 5675

Himanshu Shekhar – h.shekhar.uc@gmail.com
Department of Electrical Engineering
AB 6/327A
Indian Institute of Technology (IIT) Gandhinagar
Palaj 382355, Gujarat, India

Maxime Lafond – lafondme@ucmail.uc.edu
Department of Internal Medicine, Division of Cardiovascular Health and Disease and
Department of Biomedical Engineering
University of Cincinnati
Cardiovascular Center 3933
231 Albert Sabin Way
Cincinnati, Ohio  45267-0586

Popular version of paper 2pBA2
Presented Tuesday afternoon at 1:20 pm, May 14, 2019
177th ASA Meeting, Louisville, KY

Designer bubbles loaded with special gases are under development at the University of Cincinnati Image-guided Ultrasound Therapeutics Laboratories to treat heart disease and stroke. Xenon is a rare, pricey, heavy, noble gas, and a potent protector of a brain deprived of oxygen. Nitric oxide is a toxic gas that paradoxically plays an important role in the body, triggering the dilation of blood vessels, regulating the release and binding of oxygen in red blood cells, and even killing virus-infected cells and bacteria.

Microbubbles loaded with xenon or nitric oxide stabilized against dissolution with a fatty coating, can be exposed to ultrasound for site-specific release of these beneficial gases, as shown in the video (Supplementary Video 1). The microbubbles were stable against dissolution for for 30 minutes, which is longer than the circulation time before removal from the body. Curiously, the co-encapsulation of either of these bioactive gases with a heavier perfluorocarbon gas increased the stability of the microbubbles. Bioactive gas-loaded microbubbles act as a highlighting agent on a standard diagnostic ultrasound image (Supplementary Video 2). Triggered release was demonstrated with pulsed ultrasound already in use clinically. The total dose of xenon or nitric oxide was measured after release from the microbubbles. These results constitute the first step toward the development of ultrasound-triggered release of therapeutic gases to help rescue brain tissue during stroke.

Supplementary Video 1: High-speed video of a gas-loaded microbubble exposed to a single Doppler ultrasound pulse. Note the reduction in size over exposure to ultrasound, thus demonstrating acoustically-driven diffusion of gas out of the microbubble.

Supplementary Video 2: Ultrasound image of a rat heart filled with nitric oxide-loaded microbubbles. The chamber of the heart appears bright because of the presence of the microbubbles.

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