Editors' ChoiceCirrhosis

A Sound Treatment

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Science Translational Medicine  30 Nov 2011:
Vol. 3, Issue 111, pp. 111ec195
DOI: 10.1126/scitranslmed.3003487

In his treatise Meanings of the Intellect, the Turco-Persian psychologist and music theorist al-Farabi (872–950) discussed the therapeutic effects of music on the soul. Now, nearly a millennium later, Zhou et al. find that a new form of rock and roll—really loud sounds—has therapeutic effects on the body. Ironically, the researchers applied their emerging therapy—a technique of vascular occlusion with pulsed–high-frequency ultrasound (p-HIFU) along with proinflammatory agents—to the ear vein of a rabbit as a test system. However, the ultimate target application is treatment of gastroesophageal varices—highly dilated veins that are prone to bleeding—that develop in patients with cirrhosis of the liver.

Many patients with cirrhosis develop large blood vessels in the walls of and around the stomach and esophagus as a way of bypassing the fibrotic liver as blood returns from the gut to the heart. These so-called varices can cause life-threatening gastrointestinal bleeding. Current treatment options cannot reliably and permanently occlude the vessels and come with other complications.

p-HIFU has been shown to cause the violent collapse of microbubbles in contrast agents (cavitation), which exerts strong forces on blood vessel walls and damage the vessel endothelial surface. This in turn can serve as the nidus for clot formation. It was shown previously that local injection of the blood-clotting protein fibrinogen augments clot formation induced by cavitation. However, the body’s clot-busting fibrinolytic pathway tends to dissolve these clots quickly.

To down-regulate the fibrinolytic pathway, Zhou et al. added a new element—a proinflammatory agent, sodium morrhuate—locally to the ear vein of rabbits after intravenous injection of ultrasound microbubble contrast agents, treatment with p-HIFU, and local injection of fibrinogen. This combination therapy caused complete occlusion of the ear vein that lasted for 14 days.

The therapy described in this early study needs further development before it can be used clinically to treat gastroesophageal varices. Nevertheless, the authors have taken a sound step forward in the management of one complication of cirrhosis.

Y. Zhou et al., Targeted long-term venous occlusion using pulsed high-intensity focused ultrasound combined with a proinflammatory agent. Ultrasound Med. Biol. 37, 1653–1658 (2011). [PubMed]

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