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(Circulation Research. 1995;77:310-316.)
© 1995 American Heart Association, Inc.

Articles

Stenosis Enhances Role of Platelets in Growth of Regional Thrombus and Intimal Wall Thickening in Rat Carotid Arteries

Takehiro Igawa, Yoshie Nagamura, Yasushi Ozeki, Hideki Itoh, Fumiko Unemi

From The Third Tokushima Institute of New Drug Research (Pharmacology), Otsuka Pharmaceutical Co, Ltd, Tokushima, Japan.

Correspondence to Dr T. Igawa, Otsuka Pharmaceutical Co, Ltd, The Third Tokushima Institute of New Drug Research, 463-10 Kagasuno Kawauchi-cho, Tokushima 771-01, Japan.

Abstract The authors present the results of a study in which stenosis was induced, resulting in either thrombus or intimal wall thickening, in rat carotid arteries. At 75% stenosis in mildly denuded arteries, an acute and occlusive thrombus formation was induced, but the thrombus was significantly reduced in thrombocytopenia. Thrombus formation near the site of stenosis decreased with decreasing degree of stenosis, whereas the percent formation in the distal region (percent total thrombus) increased. Numerous mural platelet microthrombi were noted at the distal region of the stenosed arteries. After chronic 50% stenosis of the carotid artery for 2 weeks, significant intimal thickening was observed, without any occlusive thrombus formation. The combination with mild denudation was critical in eliciting the effect of stenosis. The magnitude of intimal growth in the stenosed artery was marked by day 6 and plateaued thereafter, whereas it was slight in nonstenosed arteries. The 5-bromodeoxyuridine index of the cells of the medial layer at day 3 was significantly increased by the stenosis, and the effect was reversed in thrombocytopenia. Complete reendothelialization of the intimal surface was observed by 7 to 10 days after surgery in the stenosed arteries. These findings suggest that the introduction of stenosis in these arteries enhances the interaction of platelets with the damaged arterial walls under abnormal fluid shear and that this enhancement leads to acute and occlusive thrombus formation associated with more marked stenosis as well as to sustained increase of intimal wall thickness in less marked stenosis.

Key Words: rat carotid artery • intimal wall thickening • arterial thrombosis • mild denudation • abnormal fluid shear

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