主催：日本機械学会北海道支部バイオメカニクス懇話会
共催：日本機械学会北海道支部，日本機械学会バイオエンジニアリング部門 「生体と力学ー生体への応用」研究会，JST戦略的国際科学技術協力推進事業（スウェーデン）
日 時：平成22年11月22日（月） 13:00〜14:00
場 所：北海道大学大学院工学研究科・工学部 A1-17室
講 師：氏 名 Prof. Jian Tu, Senior Lecturer
勤務先 Australian School of Advanced Medicine, Macquarie University,
Australia
演 題：Molecular targeting enhancement of radiosurgery for brain arteriovenous
malformations
内 容：Background and aim. Brain arteriovenous malformations (AVMs) are
relatively common congenital lesions that consist of tangles of immature,
poorly differentiated vessels and the major cause of haemorrhagic stroke
in children and young adults. Although some are curable, many are either
untreatable or treatable only with high surgical risk. Radiosurgery offers
the potential to treat patients who are surgically untreatable or unable
to be accessed with endovascular catheters. Radiosurgery takes 2-5 years
to obliterate all vessels within the lesion. Partial obliteration will
not reduce the risk of haemorrhagic stroke. The aim was to speed up thrombotic
process in AVM vessels post-radiosurgery. Following radiosurgery AVM vessels
undergo apoptosis. During apoptosis phosphatidylserine is translocated
to the endothelial surface, the phospholipid having “flipped” out from
the inner layers. Tissue factor binds to phosphatidylserine on the inner
vessel surface and forms a complex with factor VIIa. The factor VIIa-tissue
factor (extrinsic factor Xase) complex catalyses the activation of factor
IX and factor X, leading to the conversion of prothrombin to thrombin and
thence to the production of fibrin from fibrinogen. Our strategy was to
co-administrate tissue factors and lipopolysaccharide. The later increases
blood viscosity.
Methods. An AVM rat model was formed by anastomosis of the distal end of
the left external jugular vein to the left common carotid artery. Twenty-four
hours following radiosurgery (25Gy) animals were intravenously injected with
either soluble tissue factor, low dose lipopolysaccharide, a combination of both
or placebo. A control group received the combination of lipopolysaccharide and
soluble tissue factor following sham irradiation. Histology was used to assess
thrombus formation.
Results. Coadministration of soluble tissue factor and lipopolysaccharide
led to the formation of fibrin and erythrocyte thrombi in up to69% of small
vessels and 39% of medium sized vessels within the target region. There was no
evidence of systemic thrombus formation or toxicity in any treatment
group.
Conclusions. Treatment with soluble tissue factor and lipopolysaccharide
selectively induces thrombosis of irradiated vessels in a rat model of AVM.
Stimulation of thrombosis may improve the efficacy of radiosurgery, increasing
the treatable lesion size and reducing latency. Similar strategy may apply for
tumour therapy.