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(Circulation. 2002;105:149.)
© 2002 American Heart Association, Inc.

Brief Rapid Communications

Sonodynamic Therapy Decreased Neointimal Hyperplasia After Stenting in the Rabbit Iliac Artery

Koh Arakawa, MD; Kousukue Hagisawa, MD; Hiroyuki Kusano, MD; Satoru Yoneyama, MD; Akira Kurita, MD; Tsunenori Arai, PhD; Makoto Kikuchi, PhD; Isao Sakata, PhD; Shin-ichirou Umenura, PhD; Fumitaka Ohsuzu, MD

From Internal Medicine I (K.A., K.H., H.K., S.Y., F.O.), Medical Engineering (T.A., M.K.), and Biomedical Engineering (A.K.), National Defense Medical College, Saitama, Japan; Photochemical Co, Ltd (I.S.), Okayama, Japan; and Hitachi Research Center (S.U.), Tokyo, Japan.

Correspondence to Koh Arakawa, MD, Department Medicine I, National Defense Medical College, 3-2, Namiki, Tokorozawa, Saitama 359-8513, Japan. E-mail karakawa{at}me.ndmc.ac.jp

Background— In-stent restenosis remains a pivotal problem after coronary and peripheral stenting. Sonodynamic therapy inhibits tumor growth by means of cytotoxicity after the activation of sonochemical sensitizers by ultrasound. PAD-S31 is known to be a water-soluble, chlorin-derivative sonochemical sensitizer. We assessed the efficacy of sonodynamic therapy using this sensitizer on neointimal hyperplasia in a rabbit stent model.

Methods and Results— Stents were implanted in the iliac arteries of 16 rabbits. A total of 32 stented arteries were randomized to sonodynamic therapy, control, ultrasound exposure, and PAD-S31 groups. One hour after the intravenous administration of PAD-S31 (25 mg/kg body weight), ultrasound energy (1 MHz, 0.3 W/cm²) was delivered transdermally to the sonodynamic therapy group. At 28 days, all stent sites were analyzed morphometrically. The size of the intimal cross-sectional area was smaller in the sonodynamic therapy group than in the control, ultrasound, and PAD-S31 groups (0.31±0.07 versus 1.38±0.47, 1.66±0.71, and 1.61±0.42 mm², respectively; P<0.05). The ratio of the intimal and medial cross-sectional area was smaller in the sonodynamic therapy group than in the control, ultrasound, and PAD-S31 groups (0.71±0.22 versus 2.53±1.39, 2.48±0.60, and 3.45±1.42 mm²; P<0.05).

Conclusions— Sonodynamic therapy with PAD-S31 is considered to be a feasible treatment modality for noninvasively inhibiting neointimal hyperplasia in a rabbit iliac stent model.

Key Words: ultrasonics • stents • restenosis • sonodynamic therapy

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