Advanced Atherosclerosis Regression using Pulsed Low- Intensity Focused Ultrasound Accompanied by Atorvastatin- Loaded Microbubbles Administration

Introduction: Atherosclerosis is the leading cause of cardiovascular disease. The management of atherosclerosis reduces the risk of myocardial infarction and its related deaths.
Aims: In this study, we developed an experimental pulsed low- intensity focused ultrasound, and investigated its effectiveness on advanced atherosclerotic plaque regression accompanied by atorvastatin- loaded microbubbles administration.
Methods: Briefly, New Zealand white rabbits underwent primary balloon dilation injury at the abdominal aorta (approximately 2 cm superior to the iliac bifurcation) followed by a 1.5 % cholesterol- rich diet injury for eight weeks. Histopathology and ultrasonography results showed the formation of advanced atherosclerosis with neovessel– rich plaque and severe stenosis (> 70%) in all of the rabbits’ arteries. The animals treated by pulsed low- intensity focused ultrasound (F= 1MHz, DF= 75%, I= 3W/cm2) accompanied by high- dose atorvastatin (5mg/kg/day)- loaded PESDA (Perflurocarbon- Exposed Sonicated Dextrose Albumin) microbubbles (100 ml/kg, 2- 5 ×105 bubbles/ml) administration.
Results: Results from histology, B-mode and color Doppler ultrasonography at the stenotic region showed a significant reduction in the mean value for blood mean velocity, intraplaque neovessels density, wall mean thickness and percentage of luminal cross- sectional area of stenosis and significant increase in the mean value for blood volume flow in the treatment group compared with the other groups (p < 0.05).
Conclusion: Inertial cavitation effect of destructed PESDA microbubbles within intraplaque neovessels- induced by pulsed low- intensity focused ultrasound accompanied by the pleiotropic, lipophilic, anti-inflammatory and anti-angiogenic effects of high- dose atorvastatin administration, can cause to destroy the intraplaque neovessels, reduce the lesion macrophage- derived foam cells, increase macrophages egress and significantly dilate the luminal cross- sectional area of stenosis.