Sonoporation with doxorubicin enhances suppression of intimal hyperplasia in a vein graft model.
BACKGROUND
The purpose of the present study is to examine whether sonoporation with doxorubicin enhances suppression of intimal hyperplasia (IH) in a vein graft model.


METHODS
After the administration of 1.5 mg/kg doxorubicin intravenously, the right external jugular vein of six rabbits was exposed at 2 W/cm2 and 1 MHz of ultrasound for 2 min (Sonoporation group). Tissue doxorubicin concentration was measured. In 48 rabbits, the right common carotid artery was ligated after performing a vein graft bypass. The animals were divided into the following four groups: the C0 group (surgical procedure only); the C0S (sonoporation without doxorubicin); the C1 (doxorubicin administration only); the C1S (sonoporation with doxorubicin). Twenty-four grafts were subjected to Elastic van Gieson staining for morphometric analysis 4 weeks after the operation; others were subjected to TdT-mediated X-dUTP nick end-labeling for detection of apoptic cells and to staining with a monoclonal antibody against the proliferating cell nuclear antigen for assessment of cell proliferation 1 week after.


RESULTS
The tissue doxorubicin concentration was significantly higher in the Sonoporation group than in the Control group. Compared with the C0 group, IH was not suppressed in the C1 group but was significantly suppressed in the C1S group. Sonoporation with doxorubicin administration suppressed IH significantly (C1 group versusC1S group: P < 0.05). Cell apoptosis was induced and cell proliferation was suppressed significantly in the C1S group.


CONCLUSIONS
Sonoporation with doxorubicin suppressed IH of the vein graft. Sonoporation may be effective in coronary or peripheral revascularization using vein grafts.
Mizuno
Yoshimasa
Y
Department of Advanced Surgery, Division of Organ Pathobiology, Gifu University School of Medicine, Gifu, Japan. g2105014@guedu.cc.gifu-u.ac.jp
Iwata
Hisashi
H
Takagi
Hisato
H
Yoshikawa
Shoji
S
Umeda
Yukio
Y
Matsuno
Yukihiro
Y
Mori
Yoshio
Y
Takemura
Hirofumi
H
D000714:Anastomosis, Surgical; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000009:adverse effects / Q000493:pharmacokinetics*; D017209:Apoptosis; D017536:Carotid Artery, Common / Q000601:surgery; D002455:Cell Division; D004317:Doxorubicin / Q000009:adverse effects / Q000493:pharmacokinetics*; D006965:Hyperplasia; D020287:In Situ Nick-End Labeling; D007275:Injections, Intravenous; D007601:Jugular Veins / Q000473:pathology* / Q000637:transplantation*; D008297:Male; D011817:Rabbits; D017539:Tunica Intima / Q000473:pathology; D014465:Ultrasonics
D000903:Antibiotics, Antineoplastic; D004317:Doxorubicin