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Am J Physiol Heart Circ Physiol (August 19, 2004). doi:10.1152/ajpheart.00144.2004
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Submitted on February 12, 2004
Accepted on August 11, 2004

Microvascular Remodeling and Accelerated Hyperemia Blood Flow Restoration in Arterially Occluded Skeletal Muscle Exposed to Ultrasonic Microbubble Destruction

Ji Song1, Patrick S Cottler1, Alexander L Klibanov2, Sanjiv Kaul3, and Richard J Price1*

1 Biomedical Engineering, University of Virginia, Charlottesville, VA, USA
2 Cardiovascular Division, University of Virginia, Charlottesville, VA, USA
3 Cardiovascular Division, University of Virginia, Charlottesville, VA, USA; Biomedical Engineering, University of Virginia, Charlottesville, VA, USA

* To whom correspondence should be addressed. E-mail: rprice{at}virginia.edu.

We have previously shown that microbubble destruction with pulsed 1 MHz ultrasound creates a bioeffect that stimulates arteriogenesis and a chronic increase in hyperemia blood flow in normal rat muscle. Here, we tested whether ultrasonic microbubble destruction can be used to create a microvascular remodeling response that restores hyperemia blood flow to rat skeletal muscle affected by arterial occlusion. Pulsed ultrasound (1 MHz) was applied to gracilis muscles in which the lateral feed artery was occluded, but the medial feed artery was left intact. Control muscles were similarly occluded, but did not receive ultrasound, microbubbles, or both. Hyperemia blood flow, SM {alpha}-actin positive vessels/fiber, > 30 µm arterioles/fiber, and capillaries/fiber were determined 7, 14, and 28 days after treatment. In ultrasound-microbubble treated muscles, lateral region hyperemia blood flow was increased at all timepoints and restored to normal at day 28. SM {alpha}-actin vessels per fiber was increased over control in this region at days 7 and 14, but decreased by day 28 when larger diameter arterioles became more prevalent in the medial region. Capillaries/fiber was increased over control only at day 7 in the lateral region and only at days 7 and 14 in the medial region, indicating that the angiogenesis response was transient and likely did not contribute significantly to flow restoration at day 28. We conclude that ultrasonic microbubble destruction can be tailored to stimulate an arteriogenesis response that restores hyperemia blood flow to skeletal muscle in a rat model of arterial occlusion.




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