Regional and Conducted Vascular Effects of Endovascular Ultrasound Catheters

Intra-vascular ultrasound catheters are used clinically to facilitate clot lysis. We hypothesized that these devices could also directly lower microvascular resistance and increase tissue perfusion through established shear-dependent pathways. In mice, either the proximal hind-limb muscles or the upstream femoral artery alone was exposed to an endovascular ultrasound catheter (2.3 MHz, 0.5–1.1 MPa) for 10 min. Quantitative microvascular perfusion imaging in the hind limbs exposed to the endovascular ultrasound system exhibited a more-than-twofold increase in flow (p < 0.01) compared with the contralateral control limb after exposure of either the muscle or the femoral artery alone. Using an in vivo optical imaging reporting system, an eight- to ninefold increase in tissue adenosine triphosphate (ATP) was detected in the region of insonification (p = 0.006). Ultrasound was found to produce an immediate release of ATP from ex vivo erythrocytes (p = 0.03). In situ electrochemical sensing revealed an immediate increase in nitric oxide with initiation of ultrasound which returned to baseline within 5 min of termination, as well as ultrasound-triggered nitric oxide (NO) release from erythrocytes. These data indicate that non-cavitating ultrasound produced by endovascular catheters can reduce vascular resistance and increase flow through recognized shear-dependent vasodilator pathways involving purinergic signaling and NO.