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J Thorac Cardiovasc Surg 2002;124:621-625
© 2002 The American Association for Thoracic Surgery
Brief Communications |
From the Departments of Pharmacologya and Thoracic and Cardiovascular Surgery,b Osaka Medical College, Osaka, Japan.
Received for publication Dec 14, 2001. Accepted for publication March 24, 2002. Address for reprints: Mizuo Miyazaki, MD, Department of Pharmacology, Osaka Medical College, 2-7 Daigaku-cho, Takatsuki City, Osaka 569-8686, Japan (E-mail: pha010@art.osaka-med.ac.jp).
| The first 300 words of the full text of this article appear below. |
Coronary artery bypass grafting (CABG) has been performed on patients with ischemic heart disease to improve mortality and morbidity. In CABG the internal thoracic artery (ITA) and saphenous vein (SV) are commonly used as bypass conduits. However, the patency of venous grafts is worse than that of arterial grafts,
1-4 and its mechanism has been unclear. This stenosis, called vein graft disease, is a problem to be addressed clinically. 5,6 CABG with several arterial graft conduits, such as the radial artery, right gastroepiploic artery, and inferior epigastric artery in addition to the ITA, is clinically used to avoid vein graft disease. 7,8 However, the use of venous grafts is not yet advisable for patients who require multiple coronary revascularization or for patients undergoing a second operation. Consequently, the improvement in venous graft patency might result in further improvements in mortality and morbidity.
Angiotensin II is known to play crucial roles in the proliferation of vascular tissue in addition to the regulation of blood pressure. 9 It is known that angiotensin II is generated from angiotensin I by both angiotensin-converting enzyme (ACE) and chymasein the vascular tissue of human subjects, monkeys, dogs, and hamsters. 10-13 Our recent studies showed that chymase-dependent angiotensin II plays an important role in the development of vascular proliferation in grafted veins. 14,15 For example, we demonstrated that treatment with a chymase inhibitor, Suc-Val-Pro-Phep(Oph)2, to the vein only once before grafting could prevent the intimal hyperplasia in grafted veins 7 days after the operation in a dog model. 16 However, it has been unclear how long a chymase inhibitor used only once during the operation will suppress intimal hyperplasia in dog grafted veins. In this study we investigated the long-term effect of the chymase inhibitor Suc-Val-Pro-Phep(OPh)2 on intimal hyperplasia in dog grafted veins after bypass surgery.
Methods
Drug
A specific chymase inhibitor, Suc-Val-Pro-Phep
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