Abstract
Blood flow dynamics vary throughout the circulatory system, influencing the pathophysiology of vascular endothelium. We investigated endothelial cell response to ultrasound-stimulated microbubbles across diverse anatomical sites by mimicking assorted blood flow patterns. First, we examined the effect of culture condition on cell sensitivity to sonication by culturing HUVECs either statically or under pulsatile flow (8 or 16 dyn/cm2) for two days. Flow chambers were then co-perfused with microbubbles and propidium iodide under pulsatile flow (8 or 16 dyn/cm2) and sonicated (1MHz, 20 cycles, 1ms PRI, 300kPa) using an acoustically coupled microscope. Additionally, in a subset of studies we investigated ultrasound-assisted endothelial permeability under both pulsatile and oscillatory flow patterns. Compared to static, cells cultured under pulsatile flow resulted in 1.2 to 2.0-fold increase in the percentage of permeabilized endothelial cells (p < 0.0001). Next, compared to sonication under laminar flow (15–30 ml/min), endothelial permeability was significantly augmented under pulsatile flow, ranging from 1.3 to 2.1-fold. Additionally, compared to laminar flow, oscillatory flow at ∼16 ml/min with 0.5 Hz oscillation resulted in a 1.76-fold enhancement in cell perforation, yet yielded no observable permeability at slower flow rates (∼8 ml/min). These findings highlight the influence of local blood flow dynamics on ultrasound-mediated cell permeabilization.
Published Version
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