on August 26, 2002
Published online before print August 26, 2002, doi: 10.1161/01.CIR.0000028810.33423.95
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Submitted on March 29, 2002
From the Department of Biomedical Engineering (J.S., M.Q., S.K., R.J.P.) and the Cardiovascular Division (S.K.), University of Virginia, Charlottesville. * To whom correspondence should be addressed. E-mail: rprice{at}virginia.edu.
Background—The application of ultrasound to microbubbles in skeletal muscle creates capillary ruptures. We tested the hypothesis that this bioeffect could be used to stimulate the growth and remodeling of new arterioles via natural repair processes, resulting in an increase in skeletal muscle nutrient blood flow. Methods and Results—Pulsed ultrasound (1 MHz) was applied to exposed rat gracilis muscle after intravenous microbubble injection. Capillary rupturing was visually verified by the presence of red blood cells in the muscle, and animals were allowed to recover. Ultrasound-microbubble-treated and contralateral sham-treated muscles were harvested 3, 7, 14, and 28 days later. Arterioles were assessed by smooth muscle Conclusions—Capillary rupturing via microbubble destruction with ultrasound enhances arterioles per muscle fiber, arteriole diameters, and maximum nutrient blood flow in skeletal muscle. This method has the potential to become a clinical tool for stimulating blood flow to organs affected by occlusive vascular disease.
Revised on June 19, 2002
Accepted on June 25, 2002
Stimulation of Arteriogenesis in Skeletal Muscle by Microbubble Destruction With Ultrasound
Ji Song PhD,
-actin staining, and skeletal muscle blood flow was measured with 15-µm fluorescent microspheres. An 
65% increase in arterioles per muscle fiber was noted in treated muscles compared with paired sham-treated control muscles at 7 and 14 days after treatment. This increase in arterioles occurred across all studied diameter ranges at both 7 and 14 days after treatment. Arterioles per muscle fiber in sham-treated and untreated control muscles were comparable, indicating that the surgical intervention itself had no significant effect. Hyperemia nutrient blood flow in treated muscles was increased 57% over that in paired sham-treated control muscles.
Key words: revascularization • microcirculation • angiogenesis • ultrasonics • contrast media
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