Abstract Number: PO102
Meeting: ISTH 2021 Congress
Background: Neointimal hyperplasia is usually defined in an artery as thickening of the intimal layer after an injury such as angioplasty, stenting or surgical repair.
Aims: In this study, we developed an experimental combined β– brachytherapy and protoporphyrin IX– loaded microbubbles- mediated ultrasound sonodynamic therapy protocol, and investigated its effectiveness on neointimal hyperplasia reduction, wherein diagnostic ultrasound system is adjuncted with treatment system, with a goal of increased safety.
Methods: Briefly, rats underwent perivascular severe cold injury using liquid nitrogen at the abdominal aorta (approximately 0.5 cm superior to the iliac bifurcation). After eight weeks, the histopathology results showed progressive inflammation and smooth muscle cells proliferation in intimal layer, resulting in vessel wall thickening. Then treatment group underwent catheter- based β– brachytherapy (192Ir, 15 Gy) in combination with pulsed low level focused ultrasound (P= 15 W, PD= 250 ms)- mediated sonodynamic therapy accompanied by sonosensitizer protoporphyrin IX – loaded PESDA (Perfluorocarbon- Exposed Sonicated Dextrose Albumin) microbubbles (100ml/kg, 2-5 ×105 bubbles/ml) administration and simultaneously B- mode ultrasound imaging.
Results: Results from ultrasonography and histopathology, showed a significant reduction in the mean value for wall mean thickness and percentage of luminal cross-sectional area of stenosis at the neointimal hyperplasia region in the treatment group compared with the other groups (P< 0.05). Moreover, cell morphology with electron microscopy showed the apoptosis of smooth muscle cells in intimal layer after combination therapy.
Conclusions: Apoptotic effect of β– brachytherapy in combination with enhanced anti- inflammatory effect of protoporphyrin IX, induced by enhanced sonodynamic therapy effect of ultrasound, due to collapsed microbubbles, can cause to reduce the smooth muscle hyperplasia cells in intimal layer and significantly dilate the luminal cross-sectional area of stenosis. These findings provide the basis for developing of combined β– brachytherapy and sonodynamic therapy for a successful clinical application in the treatment of hyperplastic conditions such as restenosis.
To cite this abstract in AMA style:Mehrad H, Ahmadi Noubari H. Ultrasound-guided Catheter-based 192Ir -mediated β–brachytherapy of Neointimal Hyperplasia Accompanied by Protoporphyrin IX–loaded Microbubbles-mediated Pulsed Low Level Focused Ultrasound Sonodynamic Therapy [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/ultrasound-guided-catheter-based-192ir-mediated-%ce%b2-brachytherapy-of-neointimal-hyperplasia-accompanied-by-protoporphyrin-ix-loaded-microbubbles-mediated-pulsed-low-level-focused-ultrasoun/. Accessed December 7, 2021.
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